The latest update of Wondershare Recoverit 8.0 has been released with new and improved features. The application now provides a more intuitive user-interface and an improved data recovery algorithm.

COBIT 5 is a framework that is foundational for information technology organizations. AdOPT wants to help IT organizations harness the power of the framework by offering certification for IT professionals.

Item by Item (IBI) announced today the expansion of its Microsoft Dynamics 365 Finance and Operations online training curriculum with a new set of online courses focusing on Advanced Warehouse module.

Sterile USA LLC, a leader in space biological decontamination, announces today the advanced technology formulated to kill the COVID-19 virus (or "SARS-CoV-2") and 100% of other viruses, bacteria, and pathogens in all businesses and homes.

SmartyAds are teaming up with Protected Media within SmartHub, a white-label ad network to combat ad fraud.

Skin is the foundation of beauty. Intrinsic beauty is rooted in youthful skin. epiAGE, Inc. is launching a revolutionary direct-to-customer facial skin age service that can tell the intrinsic DNA age at specific spots on the facial skin.

Herbiar presents its natural Advanced Lash High Definition Waterproof Mascara black, composed of high-quality natural ingredients which are carefully selected after extensive research and consideration.

Transform Television Advertising into a Performance Machine. Air on Premium TV inventory in one local market or all 200 markets.

Fourth eBook in AM Focus 2020 Series Provides Unique Insights into 3D Printing with Technical Ceramics, Composites, Advanced Polymers and Refractory Metals

Announces Marshall Heitzman to Lead New Program Efforts

For all its greasy texture, the positive onion hair oil does wash off pretty well in just two washes. I have been using this hair oil for last one month once a week for around 4-5 hours. After washing, the hair does get a lot of volume and bounce. And, it lasts for a good two days which I absolutely love.

The post Positive Root Therapy + Advanced Onion Hair Oil appeared first on Perfect Skin Care for you.

On February 28, ICITAP concluded the Advanced First Aid Course at the National Highway & Motorway Police (NHMP) Training Facility in Kot Ranjit.

Lots of users have asked us about more customization and control over the sound of our audio algorithms in the past, so today, we have introduced some advanced algorithm parameters for our singletrack version in a private beta program!

• Leveler Presets are basically complete new leveling algorithms
• Maximum Loudness Range (LRA) Target to control the strength of our Leveler
• Maximum True Peak Level
• Better Hum and Noise Reduction Controls

UPDATE Nov. 2018:
We released a complete rework of the Adaptive Leveler parameters and the description here is not valid anymore!
Please see Auphonic Adaptive Leveler Customization (Beta Update)!

Please join our private beta program and let us know how you use these new features or if you need even more control!

Leveler Presets

Our Adaptive Leveler corrects level differences between speakers, between music and speech and will also apply dynamic range compression to achieve a balanced overall loudness. If you don't know about the Leveler yet, take a look at our Audio Examples.

Leveler presets are basically complete new leveling algorithms, which we have been working on in the past few months:
Our current Leveler tries to normalize all speakers to the same loudness. However, in some cases, you might want more or less loudness differences (dynamic range / loudness range) between the speakers and music segments, or more or less compression, etc.
For these use cases, we have developed additional Leveler Presets and the parameter Maximum Loudness Range.

Preset Medium:

This is our current leveling algorithm as demonstrated in the Audio Examples.

Preset Hard:

The hard preset reacts faster and applies more gain and compression compared to the medium preset. It is built for recordings with extreme loudness differences, for example very quiet questions from the audience in a lecture recording, extremely soft and loud voices within one audio track, etc.

Preset Soft:

This preset reacts slower, applies less gain and compression compared to the medium preset. Use it if you want to keep more loudness differences (dynamic narration), if you want your voices to sound "less compressed/processed", for dynamic music (concert/classical recordings), background music, etc.

Preset Softer:

Like soft, but softer :)

Preset Speech Medium, Music Soft:

Uses the medium preset in speech segments and the soft preset in music segments. It is built for music live recordings or dynamic music mixes, where you want to amplify all speakers but keep the loudness differences within and between music segments.

Preset Medium, No Compressor:

Like the medium preset, but only (mid-term) leveling and no (short-term) compression is applied. This preset is optimal if you just use a Maximum Loudness Range Target and want to avoid any additional compression as much as possible.

Maximum Loudness Range (LRA) Target

The loudness range (LRA) indicates the variation of loudness over the course of a program and is measured in LU (loudness units) - for more details see Loudness Measurement and Normalization or EBU Tech 3342.

The parameter Max Loudness Range controls how much leveling is applied:
volume changes of our Adaptive Leveler will be restricted so that the loudness range of the output file is below the selected value.
High loudness range values will result in very dynamic output files, low loudness range values in compressed output audio. If the LRA value of your input file is already below the maximum loudness range value, no leveling at all will be applied.

It is also important which Leveler Preset you select, for example, if you use the soft(er) preset, it won't be possible to achieve very low loudness range targets.

Also, the Max Loudness Range parameter is not such a precise target value as the Loudness Target. The LRA of your output file might be off a few LU, as it is not reasonable to reach the exact target value.

Use Cases: The Maximum LRA parameter allows you to control the strength of our leveling algorithms, in combination with the parameter Leveler Preset. This might be used for automatic mixdowns with different LRA values for different target platforms (very compressed ones like mobile devices or Alexa, very dynamic ones like home cinema, etc.).

Maximum True Peak Level

This parameter sets the maximum allowed true peak level of the processed output file, which is controlled by the True Peak Limiter after our Global Loudness Normalization algorithms.

If set to Auto (which is the current default), a reasonable value according to the selected loudness target is used: -1dBTP for 23 LUFS (EBU R128) and higher, -2dBTP for -24 LUFS (ATSC A/85) and lower loudness targets.

The maximum true peak level parameter is already available in our desktop program.

Better Hum and Noise Reduction Controls

Hum Base Frequency:

Set the hum base frequency to 50Hz or 60Hz (if you know it), or use Auto to automatically detect the hum base frequency in each speech region.

Hum Reduction Amount:

Maximum hum reduction amount in dB, higher values remove more noise.
In Auto mode, a classifier decides how much hum reduction is necessary in each speech region. Set it to a custom value (> 0), if you prefer more hum reduction or want to bypass our classifier. Use Disable Dehum to disable hum reduction and use our noise reduction algorithms only.

Behavior of noise and hum reduction parameter combinations:

Advanced Parameters Private Beta and Feedback

At the moment the advanced algorithm parameters are for beta users only. This is to allow us to get user feedback, so we can change the parameters to suit user needs.
Please let us know your case studies, if you need any other algorithm parameters or if you have any questions!

Here are some private beta invitation codes:

y6KCBI4yo0 ksIFEsmI1y BDZec2a21V i4XRGLlVm2 0UDxuS0vbu aaBxi35sKN aaiDSZUbmY bu8lPF80Ih eMsSl6Sf8K DaWpsUnyjo
2YM00m8zDW wh7K2pPmSa jCX7mMy2OJ ZGvvhzCpTF HI0lmGhjVO eXqVhN6QLU t4BH0tYcxY LMjQREVuOx emIogTCAth 0OTPNB7Coz
VIFY8STj2f eKzRSWzOyv 40cMMKKCMN oBruOxBkqS YGgPem6Ne7 BaaFG9I1xZ iSC0aNXoLn ZaS4TykKIa l32bTSBbAx xXWraxS40J
zGtwRJeAKy mVsx489P5k 6SZM5HjkxS QmzdFYOIpf 500AHHtEFA 7Kvk6JRU66 z7ATzwado6 4QEtpzeKzC c9qt9Z1YXx pGSrDzbEED
MP3JUTdnlf PDm2MOLJIG 3uDietVFSL 1i7jZX0Y9e zPkSgmAqqP 5OhcmHIZUP E0vNsPxZ4s FzTIyZIG2r 5EywA0M7r5 FMhpcFkVN5
oRLbRGcRmI 2LTh8GlN7h Cjw6Z3cveP fayCewjE55 GbkyX89Lxu 4LpGZGZGgc iQV7CXYwkH pGLyQPgaha e3lhKDRUMs Skrei1tKIa

If you have an invitation code, you can enter it here to activate the advanced audio algorithm parameters:
Auphonic Algorithm Parameters Private Beta Activation

Last weekend, at the Subscribe10 conference, we released Advanced Audio Algorithm Parameters for Multitrack Productions:

We launched our advanced audio algorithm parameters for Singletrack Productions last year. Now these settings (and more) are available for Multitrack Algorithms as well, which gives you detailed control for each track of your production.

• Fore/Background Settings: keep your music/clip tracks unchanged and set a custom background gain
• Multitrack Leveler Parameters: control the stereo panorama, leveling algorithm, dynamic range and compression
• Better Hum and Noise Reduction Controls for each track
• Maximum True Peak Level setting for the final mixdown
• Full API Support

Please join our private beta program and let us know how you use these new features or if you need even more control!

Fore/Background Settings

The parameter Fore/Background controls whether a track should be in foreground, in background, ducked, or unchanged, which is especially important for music or clip tracks.
For more details, please see Automatic Ducking, Foreground and Background Tracks .

Unchanged (Foreground):

We sometimes received complaints from users, which produced very complex music or clip tracks, that Auphonic changes the levels too hard.
If you set the parameter Fore/Background to the new option Unchanged (Foreground), Level relations within this track won’t be changed at all. It will be added to the final mixdown so that foreground/solo parts of this track will be as loud as (foreground) speech from other tracks.

Background Level:

It is now possible to set the level of background segments/tracks (compared to foreground segments) in background and ducking tracks. By default, background and ducking segments are 18dB softer than foreground segments.

Leveler Parameters

Similar to our Singletrack Advanced Leveler Parameters (see this previous blog post), we also released leveling parameters for Multitrack Productions now.
The following advanced parameters for our Multitrack Adaptive Leveler can be set for each track and allow you to customize which parts of the audio should be leveled, how much they should be leveled, how much dynamic range compression should be applied and to set the stereo panorama (balance):

Leveler Preset:

Select the Speech or Music Leveler for this track.
If set to Automatic (default), a classifier will decide if this is a music or speech track.

Dynamic Range:

The parameter Dynamic Range controls how much leveling is applied: Higher values result in more dynamic output audio files (less leveling). If you want to increase the dynamic range by 3dB (or LU), just increase the Dynamic Range parameter by 3dB.
For more details, please see Multitrack Leveler Parameters.

Compressor:

Select a preset for Micro-Dynamics Compression: Auto, Soft, Medium, Hard or Off.
The Compressor adjusts short-term dynamics, whereas the Leveler adjusts mid-term level differences.
For more details, please see Multitrack Leveler Parameters.

Stereo Panorama (Balance):

Change the stereo panorama (balance for stereo input files) of the current track.
Possible values: L100, L75, L50, L25, Center, R25, R50, R75 and R100.

If you understand German and want to know more about our Advanced Leveler Parameters and audio dynamics in general, watch our talk at the Subscribe10 conference:
Video: Audio Lautheit und Dynamik.

Better Hum and Noise Reduction Controls

Noise Reduction Amount:

Maximum noise and hum reduction amount in dB, higher values remove more noise.
In Auto mode, a classifier decides if and how much noise reduction is necessary (to avoid artifacts). Set to a custom (non-Auto) value if you prefer more noise reduction or want to bypass our classifier.

Hum Base Frequency:

Set the hum base frequency to 50Hz or 60Hz (if you know it), or use Auto to automatically detect the hum base frequency in each speech region.

Hum Reduction Amount:

Maximum hum reduction amount in dB, higher values remove more noise.
In Auto mode, a classifier decides how much hum reduction is necessary in each speech region. Set it to a custom value (> 0), if you prefer more hum reduction or want to bypass our classifier. Use Disable Dehum to disable hum reduction and use our noise reduction algorithms only.

Behavior of noise and hum reduction parameter combinations:

Maximum True Peak Level

In the Master Algorithm Settings of your multitrack production, you can set the maximum allowed true peak level of the processed output file, which is controlled by the True Peak Limiter after our Loudness Normalization algorithms.

If set to Auto (which is the current default), a reasonable value according to the selected loudness target is used: -1dBTP for 23 LUFS (EBU R128) and higher, -2dBTP for -24 LUFS (ATSC A/85) and lower loudness targets.

Full API Support

All advanced algorithm parameters, for Singletrack and Multitrack Productions, are available in our API as well, which allows you to integrate them into your scripts, external workflows and third-party applications.

Join the Beta and Send Feedback

Please join our beta and let us know your case studies, if you need any other algorithm parameters or if you have any questions!

Here are some private beta invitation codes:

8tZPc3T9pH VAvO8VsDg9 0TwKXBW4Ni kjXJMivtZ1 J9APmAAYjT Zwm6HabuFw HNK5gF8FR5 Do1MPHUyPW CTk45VbV4t xYOzDkEnWP
9XE4dZ0FxD 0Sl3PxDRho uSoRQxmKPx TCI62OjEYu 6EQaPYs7v4 reIJVOwIr8 7hPJqZmWfw kti3m5KbNE GoM2nF0AcN xHCbDC37O5
6PabLBRm9P j2SoI8peiY olQ2vsmnfV fqfxX4mWLO OozsiA8DWo weJw0PXDky VTnOfOiL6l B6HRr6gil0 so0AvM1Ryy NpPYsInFqm
oFeQPLwG0k HmCOkyaX9R G7DR5Sc9Kv MeQLSUCkge xCSvPTrTgl jyQKG3BWWA HCzWRxSrgW xP15hYKEDl 241gK62TrO Q56DHjT3r4
9TqWVZHZLE aWFMSWcuX8 x6FR5OTL43 Xf6tRpyP4S tDGbOUngU0 5BkOF2I264 cccHS0KveO dT29cF75gG 2ySWlYp1kp iJWPhpAimF

If you have an invitation code, you can enter it here to activate the Multitrack Advanced Audio Algorithm Parameters:
Auphonic Algorithm Parameters Private Beta Activation

It is in every case critical to pay special mind to any computerized photography insights and tips. A few people can truly take awesome photos without truly trying, yet most of us need whatever...

The power of DC electrical sources is combined onto a DC buss, such that each source behaves independently from any other source attached to the buss. In one embodiment, a converter module is attached to each of a plurality of solar photovoltaic panels and its output is attached in a parallel manner to a common buss that forms the input to a DC AC inverter. The converter module includes a Maximum Power Point Tracking component that matches the output impedance of the panels to the input impedance of the converter module. The converter also includes a communication component that provides parametric data and identification to a central inverter. Data generated by each converter module is transmitted over the power line or by wireless means and is collected at the inverter and forwarded to a data collection and reporting system.

IBM DB2 Advanced Workgroup Server Edition Restricted Use Activation V11.1 for Linux, UNIX and Windows Multilingual

See how to develop and deploy advanced Cloud Foundry applications in the IBM Cloud. Doug Tidwell shows you how to create a globally available app that uses a cloud-hosted NoSQL database.

The weather serves as both a great unifier and obsession for most Australians and now the Bureau of Meteorology is about to bring in the next generation of online forecasting technology.

(United States Federal Circuit) - In a patent infringement action, arising after two manufacturers of ambient light sensors shared technical and financial information during negotiations for a possible merger, the appeals court affirmed in part, reversed in part, and vacated in part a jury verdict for plaintiff as follows: 1) defendant's liability for trade secret misappropriation regarding a photodiode array structure was affirmed; 2) several patent infringement claims were reversed and several were affirmed; and 3) monetary damage awards were vacated and remanded for further consideration.

(United States Federal Circuit) - In a patent infringement action, arising after two manufacturers of ambient light sensors shared technical and financial information during negotiations for a possible merger, the jury verdict for plaintiff is affirmed in part, reversed in part, and vacated in part where: 1) defendant’s liability for trade secret misappropriation regarding a photodiode array structure is affirmed; 2) four patent infringement claims are reversed and four are affirmed; and 3) monetary damage awards are vacated and remanded for further consideration.

(United States Federal Circuit) - In a patent infringement action, arising after two manufacturers of ambient light sensors shared technical and financial information during negotiations for a possible merger, the appeals court affirmed in part, reversed in part, and vacated in part a jury verdict for plaintiff as follows: 1) defendant's liability for trade secret misappropriation regarding a photodiode array structure was affirmed; 2) several patent infringement claims were reversed and several were affirmed; and 3) monetary damage awards were vacated and remanded for further consideration.

(United States Ninth Circuit) - Held that an employee of the California State Board of Equalization violated clearly established law by participating in law enforcement's execution of a search warrant at the business premises of a man with whom he had a recent altercation. Affirmed the denial of his motion seeking qualified immunity in this lawsuit alleging civil rights and tort claims.

(United States Federal Circuit) - In a patent infringement action, arising after two manufacturers of ambient light sensors shared technical and financial information during negotiations for a possible merger, the appeals court affirmed in part, reversed in part, and vacated in part a jury verdict for plaintiff as follows: 1) defendant's liability for trade secret misappropriation regarding a photodiode array structure was affirmed; 2) several patent infringement claims were reversed and several were affirmed; and 3) monetary damage awards were vacated and remanded for further consideration.

TRB's Airport Cooperative Research Program (ACRP) Research Report 155: Guidebook for Advanced Computerized Maintenance Management System Integration at Airports explores the use of a Computerized Maintenance Management System (CMMS) to manage a variety of assets across a number of different airport systems. This report develops guidance on the steps necessary to implement a CMMS, factors for consideration in prioritizing which systems should be included in the CMMS using a phased approach, and the steps ...

BACKGROUND The anti–programmed cell death 1 (anti–PD-1) antibody pembrolizumab is clinically active against non–small cell lung cancer (NSCLC). In addition to T cells, human natural killer (NK) cells, reported to have the potential to prolong the survival of patients with advanced NSCLC, also express PD-1. This study aimed to investigate the safety and efficacy of pembrolizumab plus allogeneic NK cells in patients with previously treated advanced NSCLC.METHODS In total, 109 enrolled patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1% or higher were randomly allocated to group A (n = 55 patients given pembrolizumab plus NK cells) or group B (n = 54 patients given pembrolizumab alone). The patients received i.v. pembrolizumab (10 mg/kg) once every 3 weeks and continued treatment until the occurrence of tumor progression or unacceptable toxicity. The patients in group A continuously received 2 cycles of NK cell therapy as 1 course of treatment.RESULTS In our study, patients in group A had longer survival than did patients in group B (median overall survival [OS]: 15.5 months vs. 13.3 months; median progression-free survival [PFS]: 6.5 months vs. 4.3 months; P < 0.05). In group A patients with a TPS of 50% or higher, the median OS and PFS was significantly longer. Moreover, the patients in group A treated with multiple courses of NK cell infusion had better OS (18.5 months) than did those who received a single course of NK cell infusion (13.5 months).CONCLUSIONS Pembrolizumab plus NK cell therapy yielded improved survival benefits in patients with previously treated PD-L1+ advanced NSCLC.TRIAL REGISTRATION ClinicalTrials.gov NCT02843204.FUNDING This work was supported by grants from the National Natural Science Foundation of China (NSFC) – Guangdong Joint Foundation of China (no. U1601225); the NSFC (no. 81671965); the Guangdong Provincial Key Laboratory Construction Project of China (no. 2017B030314034); and the Key Scientific and Technological Program of Guangzhou City (no. 201607020016).

IBM today unveiled its next-generation Power Systems Servers incorporating its newly designed POWER9 processor. Built specifically for compute-intensive AI workloads, the new POWER9 systems are capable of improving the training times of deep learning frameworks by nearly 4x allowing enterprises to build more accurate AI applications, faster.

IBM (NYSE: IBM) today announced the launch of the IBM Institute for Advanced Security in Asia-Pacific, an expansion of its company-wide initiative to provide governments, businesses and other key organisations with a forum to collaborate with IBM’s global network of security research, services, software and technology experts.

IBM (NYSE: IBM) today announced that the University of Melbourne, a world class research university, has selected IBM to design and install a high efficiency, high density cooling solution to support new IT initiatives such as Cloud and Research computing, in its new data centre, Data Hall 2.

Ann, Bill, and their beautiful animal-filled family. If you are a pet owner(dogs, cats, pigs, goats, birds, turtles, horses, chickens, pigs…) over the age 60 with great style, send photos to Advancedstyleinfo@gmail.com. I’m looking for fun subjects for a future project. Apologies in advance if I can’t get back to everyone right away!

The post Advanced Pets: Ann and Bill appeared first on Advanced Style.

The post Advanced Pets: Mara and Bruiser appeared first on Advanced Style.

Now you can specify a pool of hashtags, and random hashtags from your pool will be added to your posts.

The post Advanced Hashtags Feature Will Enhance Your Automated Posting appeared first on RSSground.com.

Best known for their aluminum products, Newmen's new carbon fiber wheelset is aimed at enduro riders.
( Photos: 10, Comments: 96 )

All the latest rumours and gossip coming out of Manchester United, Chelsea, Liverpool, Arsenal, Barcelona and Real Madrid.

Netgem announced that Sure has partnered with Netgem to launch a new hybrid IPTV service for its customers in the Channel Islands and the Isle of Man.

By working with Netgem, Sure has been able to make use of its broadband network to deliver Over the Top live and non-linear content to a hybrid STB. This means the operator can now add premium TV to its bouquet of services and offer its customers triple and quad play packages.

The new service is powered by Netgem's N8200 hybrid PVR integrating its nCloud middleware; subscribers will benefit from a brand-new TV experience that supplements UK DVB-T2 free-to-air channels for popular non-linear entertainment content and a fluid and consistent user interface.

Joshua Summers, CEO of linear television supply-side platform clypd, discusses the major advanced targeting trends expected to infiltrate traditional TV ad buying within the next year.

Peggy Yarborough
Jan 1, 2003; 16:
Case Studies

Geralyn Spollett
Jan 1, 2003; 16:
Case Studies

Introduction: To use positron emission tomography coupled with computed tomography (¹⁸FDG-PET/CT) to identify a high-risk subgroup requiring therapeutic intensification among patients with locally advanced cervical cancer (LACC) and para-aortic lymph node (PALN) involvement. Methods: In this retrospective multicentric study, patients with LACC and PALN involvement concurrently treated with chemoradiotherapy and extended-field radiotherapy (EFR) between 2006 and 2016 were included. A senior nuclear medicine specialist in PET for gynaecologic oncology reviewed all ¹⁸FDG-PET/CT scans. Metabolic parameters including maximum standardised uptake value (SUV_max), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were determined for the primary tumour, pelvic lymph nodes and PALN. Associations between these parameters and overall survival (OS) were assessed with Cox's proportional hazards model. Results: Sixty-eight patients were enrolled in the study. Three-year OS was 55.5% (95% CI (40.8-68.0)). When adjusted for age, stage and histology, pelvic lymph node TLG, PALN TLG and PALN SUV_max were significantly associated with OS (p<0.005). Conclusion: FDG-PET/CT was able to identify predictors of survival in the homogeneous subgroup of patients with LACC and PALN involvement, thus allowing therapeutic intensification to be proposed.

The aim of this work was to quantify the uptake of [¹⁸F]BMS-986192, a PD-L1 adnectin PET tracer, in patients with non-small-cell lung cancer (NSCLC). To this end, plasma input kinetic modeling of dynamic tumor uptake data with online arterial blood sampling was performed. In addition, the accuracy of simplified uptake metrics such as standardized uptake value (SUV) was investigated. Methods: Data from a study with [¹⁸F]BMS-986192 in patients with advanced stage NSCLC eligible for nivolumab treatment were used if a dynamic scan was available and lesions were present in the field of view of the dynamic scan. After injection of [¹⁸F]BMS-986192, a 60-minutes dynamic PET-CT scan was started, followed by a 30-min whole body PET-CT scan. Continuous arterial and discrete arterial and venous blood sampling were performed to determine a plasma input function. Tumor time activity curves were fitted by several plasma input kinetic models. Simplified uptake parameters included tumor to blood ratio as well as several SUV measures. Results: Twenty two tumors in nine patients were analyzed. The arterial plasma input single-tissue reversible compartment model with fitted blood volume fraction seems to be the most preferred model as it best fitted 11 out of 18 tumor time activity curves. The distribution volume V_T ranged from 0.4 to 4.8 mL·cm-3. Similar values were obtained with an image derived input function. From the simplified measures, SUV normalized for body weight (SUV_BW) at 50 and 67 minutes post injection correlated best with V_T, with an R² > 0.9. Conclusion: A single tissue reversible model can be used for the quantification of tumor uptake of the PD-L1 PET tracer [¹⁸F]BMS-986192. SUV_BW at 60 minutes post injection, normalized for body weight, is an accurate simplified parameter for uptake assessment of baseline studies. In order to assess its predictive value for response evaluation during PD-(L)1 immune checkpoint inhibition further validation of SUV against V_T based on an image derived input function is recommended.

The objective of this retrospective study was to determine the role of ¹⁸F-FDG PET/CT in a large cohort of 495 patients with metastatic neuroendocrine neoplasms (NENs) who were treated with peptide receptor radionuclide therapy (PRRT) with a long-term follow-up. Methods: The 495 patients were treated with ¹⁷⁷Lu- and/or ⁹⁰Y- DOTATOC/DOTATATE PRRT between 2/2002 and 7/2018. All subjects received both ⁶⁸Ga-DOTATOC/TATE/NOC and ¹⁸F-FDG PET/CT prior to treatment and were followed 3-189 months. Kaplan-Meier analysis, log-rank test (Mantel-Cox), and Cox regression analysis were performed for overall survival (OS) and progression-free survival (PFS). Results: 199 patients (40.2%) presented with pancreatic NEN, 49 with CUP (cancer of unknown primary), 139 with midgut NEN, whereas the primary tumor was present in the rectum in 20, in the lung in 38, in the stomach in 8 and other locations in 42 patients. FDG-PET/CT was positive in 382 (77.2%) patients and 113 (22.8%) were FDG-negative before PRRT, while 100% were ⁶⁸Ga-DOTATOC/TATE/NOC positive. For all patients, the median PFS and OS, defined from start of PRRT, were 19.6 mo and 58.7 mo, respectively. Positive FDG predicted shorter PFS (18.5 mo vs 24.1 mo; P = 0.0015) and OS (53.2 mo vs 83.1 mo; P < 0.001) than negative FDG. Amongst the pancreatic NEN, the median OS was 52.8 mo in FDG positive and 114.3 mo in FDG negative subjects (P = 0.0006). For all patients with positive ¹⁸F-FDG uptake, and a ratio of the highest SUV_max on ⁶⁸Ga-SSTR PET to the most ¹⁸F-FDG-avid tumor lesions >2, the median OS was 53.0 mo, compared to 43.4 mo in those patients with a ratio <2 (P = 0.030). For patients with no ¹⁸F-FDG uptake (complete "mismatch" imaging pattern), the median OS was 108.3 mo vs 76.9 mo for SUV_max >15.0 and ≤15.0 on ⁶⁸Ga-SSTR PET/CT, respectively. Conclusion: The presence of positive lesions on ¹⁸F-FDG PET is an independent prognostic factor in patients with NEN treated with PRRT. Metabolic imaging with ¹⁸F-FDG PET/CT compliments the molecular imaging aspect of ⁶⁸Ga-SSTR PET/CT for the prognosis of survival after PRRT. High SSTR expression combined with negative ¹⁸F-FDG PET/CT imaging is associated with the most favorable long-term prognosis.

Introduction: Neuroendocrine differentiation is associated with treatment failure and poor outcome in metastatic castration-resistant prostate cancer (mCRPC). We investigated the effect of circulating neuroendocrine biomarkers on the efficacy of PSMA-targeted radioligand therapy (RLT). Methods: Neuroendocrine biomarker profiles (progastrin-releasing peptide, neuron-specific enolase, and chromogranin-A) were analyzed in 50 patients commencing ¹⁷⁷Lu-PSMA-617 RLT. The primary endpoint was PSA response in relation to baseline neuroendocrine marker profiles. Additional endpoints included progression-free survival. Tumor uptake on post-therapeutic scans, a known predictive marker for response, was used as control-variable. Results: Neuroendocrine biomarker profiles were abnormal in the majority of patients. Neuroendocrine biomarker levels did not predict treatment failure or early progression (P ≥ 0.13). By contrast, intense PSMA-ligand uptake in metastases predicted both treatment response (P = 0.0030) and reduced risk of early progression (P = 0.0111). Conclusion: Neuroendocrine marker profiles do not predict adverse outcome of RLT. By contrast, high ligand uptake was confirmed to be crucial for achieving tumor-response.

Prostate specific membrane antigen (PSMA) targeting Positron Emission Tomography (PET) imaging is becoming the reference standard for prostate cancer (PC) staging, especially in advanced disease. Yet, the implications of PSMA-PET derived whole-body tumor volume for overall survival are poorly elucidated to date. This might be due to the fact that (semi-) automated quantification of whole-body tumor volume as PSMA-PET biomarker is an unmet clinical challenge. Therefore, a novel semi-automated software is proposed and evaluated by the present study, which enables the semi-automated quantification of PSMA-PET biomarkers such as whole-body tumor volume. Methods: The proposed quantification is implemented as a research prototype (MI Whole Body Analysis Suite, v1.0, Siemens Medical Solutions USA, Inc., Knoxville, TN). PSMA accumulating foci were automatically segmented by a percental threshold (50% of local SUV_max). Neural networks were trained to segment organs in PET-CT acquisitions (training CTs: 8,632, validation CTs: 53). Thereby, PSMA foci within organs of physiologic PSMA uptake were semi-automatically excluded from the analysis. Pretherapeutic PSMA-PET-CTs of 40 consecutive patients treated with ¹⁷⁷Lu-PSMA-617 therapy were evaluated in this analysis. The volumetric whole-body tumor volume (PSMATV50), SUV_max, SUVmean and other whole-body imaging biomarkers were calculated for each patient. Semi-automatically derived results were compared with manual readings in a sub-cohort (by one nuclear medicine physician using syngo.MM Oncology software, Siemens Healthineers, Knoxville, TN). Additionally, an inter-observer evaluation of the semi-automated approach was performed in a sub-cohort (by two nuclear medicine physicians). Results: Manually and semi automatically derived PSMA metrics were highly correlated (PSMATV50: R2=1.000; p<0.001; SUV_max: R2=0.988; p<0.001). The inter-observer agreement of the semi-automated workflow was also high (PSMATV50: R2=1.000; p<0.001; ICC=1.000; SUV_max: R2=0.988; p<0.001; ICC=0.997). PSMATV50 [ml] was a significant predictor of overall survival (HR: 1.004; 95%CI: 1.001-1.006, P = 0.002) and remained so in a multivariate regression including other biomarkers (HR: 1.004; 95%CI: 1.001-1.006 P = 0.004). Conclusion: PSMATV50 is a promising PSMA-PET biomarker that is reproducible and easily quantified by the proposed semi-automated software. Moreover, PSMATV50 is a significant predictor of overall survival in patients with advanced prostate cancer that receive ¹⁷⁷Lu-PSMA-617 therapy.

In randomized clinical trials (RCTs), no survival benefit has been observed for selective internal radiotherapy (SIRT) over sorafenib in patients with advanced hepatocellular carcinoma (aHCC). This study aimed to assess by means of a meta-analysis whether overall survival (OS) with SIRT, as monotherapy or followed by sorafenib, is non-inferior to sorafenib, and compare safety profiles for patients with aHCC. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library up to February 2019 to identify RCTs comparing SIRT as monotherapy, or followed by sorafenib, to sorafenib monotherapy among patients with aHCC. The main outcomes were OS and frequency of treatment-related severe adverse events (AEs grade ≥3). The per-protocol population was the primary analysis population. A non-inferiority margin of 1.08 in terms of hazard ratio (HR) was pre-specified for the upper boundary of 95% confidence interval (CI) for OS. Pre-specified subgroup analyses were performed. Results: Three RCTs, involving 1,243 patients, comparing sorafenib with SIRT (SIRveNIB and SARAH) or SIRT followed by sorafenib (SORAMIC), were included. After randomization, 411/635 (64.7%) patients allocated to SIRT and 522/608 (85.8%) allocated to sorafenib completed the studies without major protocol deviations. Median OS with SIRT, whether or not followed by sorafenib, was non-inferior to sorafenib (10.2 and 9.2 months, [HR 0.91, 95% CI 0.78–1.05]). Treatment-related severe adverse events were reported in 149/515 patients (28.9%) who received SIRT and 249/575 (43.3%) who received sorafenib only (p<0.01). Conclusion: SIRT as initial therapy for aHCC is non-inferior to sorafenib in terms of OS, and offers a better safety profile.

Melpomeni Peppa
Oct 1, 2003; 21:
Council's Voice

As governments seek to push their borders out by amassing ever more data on travelers and migrants, their creation of increasingly complex border surveillance systems and use of risk-assessment technologies could ease mobility for some while rendering other groups immobile based on hypothetical risk profiles and decisions that are not publicly known and cannot be challenged, as this article explores.