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Purpose: With the advent of highly efficacious time-limited combination treatments of targeted agents in chronic lymphocytic leukemia (CLL), minimal residual disease (MRD) assessment has gained importance as a measure for therapeutic success and as a surrogate for progression-free survival. The currently most widely used method is multicolor flow cytometry, which detects circulating CLL cells in the peripheral blood. However, it seems to be less sensitive for the detection of MRD in the lymph node compartment. Patients and Methods: To evaluate whether a cell-free approach can overcome this limitation, we performed serial assessments of circulating tumor DNA (ctDNA) in patients with CLL treated with obinutuzumab, acalabrutinib, and venetoclax in the phase II CLL2-BAAG trial. Patient-specific variability, diversity, joining (VDJ) rearrangements as well as somatic driver mutations were tracked before, during and after treatment by digital droplet PCR in blood plasma. Furthermore, these were systematically compared to matched flow cytometry data. Results: In the 381 sample pairs, ctDNA and flow cytometry yielded highly concordant results. However, clone-specific ctDNA was detected in 44 of 152 samples (29%) that were assessed as undetectable MRD (uMRD) by flow cytometry (defined as less than one CLL cell in 10,000 normal leukocytes). 29 ctDNA-negative samples showed detectable MRD >10–4 by flow cytometry. Also, somatic driver mutations were detected with a similar sensitivity compared with patient-specific VDJ rearrangements in plasma. In patients with predominantly nodal residual disease, ctDNA compared favorably with 4-color flow cytometry and seemed to more accurately reflect the entire disease burden across compartments. Conclusions: On the basis of these findings, ctDNA-based MRD assessment appears to be a promising method to complement cell-based MRD approaches like flow cytometry that focus on circulating CLL cells in the peripheral blood.

Supplementary Data from Circulating Tumor DNA–Based MRD Assessment in Patients with CLL Treated with Obinutuzumab, Acalabrutinib, and Venetoclax

Purpose:With the advent of highly efficacious time-limited combination treatments of targeted agents in chronic lymphocytic leukemia (CLL), minimal residual disease (MRD) assessment has gained importance as a measure for therapeutic success and as a surrogate for progression-free survival. The currently most widely used method is multicolor flow cytometry, which detects circulating CLL cells in the peripheral blood. However, it seems to be less sensitive for the detection of MRD in the lymph node compartment.Patients and Methods:To evaluate whether a cell-free approach can overcome this limitation, we performed serial assessments of circulating tumor DNA (ctDNA) in patients with CLL treated with obinutuzumab, acalabrutinib, and venetoclax in the phase II CLL2-BAAG trial. Patient-specific variability, diversity, joining (VDJ) rearrangements as well as somatic driver mutations were tracked before, during and after treatment by digital droplet PCR in blood plasma. Furthermore, these were systematically compared to matched flow cytometry data.Results:In the 381 sample pairs, ctDNA and flow cytometry yielded highly concordant results. However, clone-specific ctDNA was detected in 44 of 152 samples (29%) that were assessed as undetectable MRD (uMRD) by flow cytometry (defined as less than one CLL cell in 10,000 normal leukocytes). 29 ctDNA-negative samples showed detectable MRD >10–4 by flow cytometry. Also, somatic driver mutations were detected with a similar sensitivity compared with patient-specific VDJ rearrangements in plasma. In patients with predominantly nodal residual disease, ctDNA compared favorably with 4-color flow cytometry and seemed to more accurately reflect the entire disease burden across compartments.Conclusions:On the basis of these findings, ctDNA-based MRD assessment appears to be a promising method to complement cell-based MRD approaches like flow cytometry that focus on circulating CLL cells in the peripheral blood.

Eine etablierte Methode der Sicherheitsforschung zur Feststellung von Schwachstellen in Software ist Reverse Engineering. Verstost eine solche Analyse von Programmen gegen das Urheberrecht? Mehrere deutsche Forscherteams erhielten nach der Veroffentlichung von gefundenen Schwachstellen Unterlassungserklarungen sowie Antrage auf einstweilige Verfugung von einem Anbieter von Sicherheitssoftware.

Bluetooth provides encryption, authentication, and integrity protection of its connections. These protection mechanisms require that Bluetooth devices initially establish trust on first use through a process called pairing. Throughout this process, multiple alternative pairing methods are supported.In this paper, we describe a design flaw in the pairing mechanism of Bluetooth. This flaw permits two devices to perform pairing using differing methods. While successfully interacting with each other, the devices are not aware of the Method Confusion. We explain how an attacker can cause and abuse this Method Confusion to mount a Method Confusion Attack. In contrast to other attacks targeting the pairing method, our attack applies even in Bluetooth’s highest security mode and cannot be mitigated in the protocol. Through the Method Confusion Attack, an adversary can infiltrate the secured connection between the victims and intercept all traffic.Our attack is successful in practically relevant scenarios. We implemented it as an end-to-end Proof of Concept for Bluetooth Low Energy and tested it with off-the-shelf smartphones, a smartwatch and a banking device. Furthermore, we performed a user study where none of the 40 participants noticed the ongoing attack, and 37 (92.5%) of the users completed the pairing process. Finally, we propose changes to the Bluetooth specification that immunize it against our attack.

To secure mobile devices, such as laptops and smartphones, against unauthorized physical data access, employing Full Disk Encryption (FDE) is a popular defense. This technique is effective if the device is always shut down when unattended. However, devices are often suspended instead of switched off. This leaves confidential data such as the FDE key, passphrases and user data in RAM which may be read out using cold boot, JTAG or DMA attacks. These attacks can be mitigated by encrypting the main memory during suspend. While this approach seems promising, it is not implemented on Windows or Linux. We present FridgeLock to add memory encryption on suspend to Linux. Our implementation as a Linux Kernel Module (LKM) does not require an admin to recompile the kernel. Using Dynamic Kernel Module Support (DKMS) allows for easy and fast deployment on existing Linux systems, where the distribution provides a prepackaged kernel and kernel updates. We tested our module on a range of 4.19 to 5.3 kernels and experienced a low performance impact, sustaining the system's usability. We hope that our tool leads to a more detailed evaluation of memory encryption in real world usage scenarios.

On Linux, most---if not all---debuggers use ptrace debugging API to control their target processes. However, ptrace proves unsatisfactory for many malware analysis and reverse engineering tasks: So-called split-personality malware often adapts its behavior in the presence of a debugger, yet ptrace makes no attempt to hide from a target process. Furthermore, ptrace enforces a strict one-to-many relation meaning that while each tracer can trace many tracees, each tracee can only be controlled by at most one tracer. Simultaneously, the complex API and signal-based communications provide opportunities for erroneous usage.Previous works have identified the newer uprobes tracing API as a candidate for building a replacement for ptrace, but ultimately rejected it due to lack of practical use and documentation. Building upon uprobes, we introduce plutonium-dbg, a Linux kernel module providing debugging facilities independent of the limitations of ptrace alongside a GDB-compatible interface. Our approach aims to mitigate some of the design flaws of ptrace that make it both hard to use and easy to detect by malicious software.We show how plutonium-dbg's design and implementation remove many of the most frequently named issues with ptrace, and that our method improves on traditional ptrace-based debuggers (GDB and LLDB) when evaluated on software samples that attempt to detect the presence of a debugger.

With the increasing use of Ethernet-based communication backbones in safety-critical real-time domains, both efficient and predictable interfacing and cryptographically secure authentication of high-speed data streams are becoming very important. Although the increasing data rates of in-vehicle networks allow the integration of more demanding (e.g., camera-based) applications, processing speeds and, in particular, memory bandwidths are no longer scaling accordingly. The need for authentication, on the other hand, stems from the ongoing convergence of traditionally separated functional domains and the extended connectivity both in- (e.g., smart-phones) and outside (e.g., telemetry, cloud-based services and vehicle-to-X technologies) current vehicles. The inclusion of cryptographic measures thus requires careful interface design to meet throughput, latency, safety, security and power constraints given by the particular application domain. Over the last decades, this has forced system designers to not only optimize their software stacks accordingly, but also incrementally move interface functionalities from software to hardware. This paper discusses existing and emerging methods for dealing with high-speed data streams ranging from software-only via mixed-hardware/software approaches to fully hardware-based solutions. In particular, we introduce two approaches to acquire and authenticate GigE Vision Video Streams at full line rate of Gigabit Ethernet on Programmable SoCs suitable for future heterogeneous automotive processing platforms.