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Background Fragility fractures without significant trauma of the pelvic ring in older patients were often treated conservatively. An alternative treatment is surgery involving percutaneous screw fixation to stabilize the posterior pelvic ring. This surgical treatment enables patients to be mobilized quickly and complications associated with bedrest and temporary immobility are reduced. However, the functional outcome following surgery and quality of life of the patients have not yet been investigated. Here, we present a comprehensive study addressing the long-term well-being and the quality of life of patients with fragility pelvic ring fractures after surgical treatment. Methods Between 2011–2019, 215 geriatric patients with pelvic ring fractures were surgically treated at the university hospital in Göttingen (Germany). Of these, 94 patients had fragility fractures for which complete sets of computer tomography (CT) and radiological images were available. Fractures were classified according to Tile and according to the FFP classification of Rommens and Hofmann. The functional outcome of surgical treatment was evaluated using the Majeed pelvic score and the Short Form Health Survey-36 (SF-36). Results Thirty five tile type C and 48 type B classified patients were included in the study. After surgery eighty-three patients scored in average 85.92 points (± 23.39) of a maximum of 100 points using the Majeed score questionnaire and a mean of 1.60 points on the numerical rating scale ranging between 0 and 10 points where 0 points refers to “no pain” and 10 means “strongest pain”. Also, the SF-36 survey shows that surgical treatment positively effects patients with respect to their general health status and by restoring vitality, reducing bodily pain and an increase of their general mental health. Conclusions Patients who received a percutaneous screw fixation of fragility fractures of the posterior pelvic ring reported an overall positive outcome concerning their long-term well-being. In particular, older patients appear to benefit from surgical treatment. Trial registration Functional outcome and quality of life after surgical treatment of fragility fractures of the posterior pelvic ring, DRKS00024768. Registered 8th March 2021 - Retrospectively registered. Trial registration number DRKS00024768 .

PurposeReduction and percutaneous screw fixation of sacroiliac joint disruptions and sacral fractures are surgical procedures for stabilizing the posterior pelvic ring. It is unknown, however, whether smaller irregularities or the inability to achieve an anatomic reduction of the joint and the posterior pelvic ring affects the functional outcome. Here, the long-term well-being of patients with and without anatomic reduction of the posterior pelvis after sacroiliac joint disruptions is described.MethodsBetween 2011 and 2017, 155 patients with pelvic injuries underwent surgical treatment. Of these, 39 patients with sacroiliac joint disruption were examined by radiological images and computer tomography (CT) diagnostics and classified according to Tile. The functional outcome of the different surgical treatments was assessed using the short form health survey-36 (SF-36) and the Majeed pelvic score.ResultsComplete data sets were available for 31 patients, including 14 Tile type C and 17 type B injuries. Of those, 26 patients received an anatomic reduction, 5 patients obtained a shift up to 10 mm (range 5–10 mm). The SF-36 survey showed that the anatomic reduction was significantly better in restoring the patient’s well being (vitality, bodily pain, general mental health and emotional well-being). Patients without this treatment reported a decrease in their general health status.ConclusionsAnatomic reduction was achieved in over 80% of patients in this study. When comparing the long-term well-being of patients with and without anatomic reduction of the posterior pelvis after sacroiliac joint disruptions, the results suggest that anatomical restoration of the joint is beneficial for the patients.

The aim of this study is to determine the critical time intervals and influencing covariates for in-hospital mortality in geriatric trauma and orthopedic patients. During a period of five years, we retrospectively review patients aged > 60 years who were hospitalized at the Department of Trauma, Orthopedic, and Plastic Surgery. The primary outcome is the mean time to death. Survival analysis is performed using an accelerated failure time model. A total of 5388 patients are included in the analysis. Two-thirds underwent surgery (n = 3497, 65%) and one-third were conservatively treated (n = 1891, 35%). The in-hospital mortality rate is 3.1% (n = 168; surgery, n = 112; conservative, n = 56). The mean time to death is 23.3 days (±18.8) after admission in the surgery group and 11.3 days (±12.5) in the conservative treatment group. The greatest accelerating effect on mortality is found in the intensive care unit (16.52, p < 0.001). We are able to identify a critical time interval for in-hospital mortality between days 11 and 23. The day of death on weekend days/holidays, hospitalization for conservative treatment, and treatment at the intensive care unit significantly increase the risk of in-hospital mortality. Early mobilization and a short hospitalization duration seem to be of major importance in fragile patients.

A correction to this paper has been published: https://doi.org/10.1007/s00068-021-01698-w

The cryptocurrency Ethereum is the most widely used execution platform for smart contracts. Smart contracts are distributed applications, which govern financial assets and, hence, can implement advanced financial instruments, such as decentralized exchanges or autonomous organizations (DAOs). Their financial nature makes smart contracts an attractive attack target, as demonstrated by numerous exploits on popular contracts resulting in financial damage of millions of dollars. This omnipresent attack hazard motivates the need for sound static analysis tools, which assist smart contract developers in eliminating contract vulnerabilities a priori to deployment. Vulnerability assessment that is sound and insightful for EVM contracts is a formidable challenge because contracts execute low-level bytecode in a largely unknown and potentially hostile execution environment. So far, there exists no provably sound automated analyzer that allows for the verification of security properties based on program dependencies, even though prevalent attack classes fall into this category. In this work, we present HoRStify, the first automated analyzer for dependency properties of Ethereum smart contracts based on sound static analysis. HoRStify grounds its soundness proof on a formal proof framework for static program slicing that we instantiate to the semantics of EVM bytecode. We demonstrate that HoRStify is flexible enough to soundly verify the absence of famous attack classes such as timestamp dependency and, at the same time, performant enough to analyze real-world smart contracts.

Vortex rings are remarkably stable structures that occur in a large variety of systems, such as in turbulent gases (where they are at the origin of weather phenomena)1, fluids (with implications for biology)2, electromagnetic discharges3 and plasmas4. Although vortex rings have also been predicted to exist in ferromagnets5, they have not yet been observed. Using X-ray magnetic nanotomography6, we imaged three-dimensional structures forming closed vortex loops in a bulk micromagnet. The cross-section of these loops consists of a vortex–antivortex pair and, on the basis of magnetic vorticity (a quantity analogous to hydrodynamic vorticity), we identify these configurations as magnetic vortex rings. Although such structures have been predicted to exist as transient states in exchange ferromagnets5, the vortex rings we observe exist as static configurations, and we attribute their stability to the dipolar interaction. In addition, we observe stable vortex loops intersected by point singularities7 at which the magnetization within the vortex and antivortex cores reverses. We gain insight into the stability of these states through field and thermal equilibration protocols. The observation of stable magnetic vortex rings opens up possibilities for further studies of complex three-dimensional solitons in bulk magnets, enabling the development of applications based on three-dimensional magnetic structures.Three-dimensional structures of vortex loops in a bulk micromagnet GdCo2 have been observed using X-ray magnetic nanotomography. The cross-section of these loops consists of a vortex–antivortex pair stabilized by the dipolar interaction.

The authors report the first-in-human application of personalized neo-antigen RNA vaccines in patients with melanoma. Personalized cancer vaccine trials Neoantigens have long been considered optimal targets for anti-tumour vaccines, and recent mutation coding and prediction techniques have aimed to streamline their identification and selection. Two papers in this issue report results from personalized neoantigen vaccine trials in patients with cancer. Catherine Wu and colleagues report the results of a phase I trial of a personalized cancer vaccine that targets up to 20 patient neoantigens. The vaccine was safe and induced tumour-antigen-specific immune responses. Four out of six patients treated showed no recurrence at 25 months, and progressing patients responded to further therapy with checkpoint inhibitor. Ugur Sahin and colleagues report the first-in-human application of a personalized neoantigen vaccine in patients with melanoma. Their vaccination strategy includes sequencing and computational identification of neoantigens from patients, and design and manufacture of a poly-antigen RNA vaccine for treatment. In 13 patients, the vaccine boosted immunity against some of the selected tumour antigens from the individual patients, and two patients showed infiltration of tumour-reactive T cells. These results suggest that personalized vaccines could be refined and tailored to provide clinical benefit as cancer immunotherapies. T cells directed against mutant neo-epitopes drive cancer immunity. However, spontaneous immune recognition of mutations is inefficient. We recently introduced the concept of individualized mutanome vaccines and implemented an RNA-based poly-neo-epitope approach to mobilize immunity against a spectrum of cancer mutations 1 , 2 . Here we report the first-in-human application of this concept in melanoma. We set up a process comprising comprehensive identification of individual mutations, computational prediction of neo-epitopes, and design and manufacturing of a vaccine unique for each patient. All patients developed T cell responses against multiple vaccine neo-epitopes at up to high single-digit percentages. Vaccine-induced T cell infiltration and neo-epitope-specific killing of autologous tumour cells were shown in post-vaccination resected metastases from two patients. The cumulative rate of metastatic events was highly significantly reduced after the start of vaccination, resulting in a sustained progression-free survival. Two of the five patients with metastatic disease experienced vaccine-related objective responses. One of these patients had a late relapse owing to outgrowth of β2-microglobulin-deficient melanoma cells as an acquired resistance mechanism. A third patient developed a complete response to vaccination in combination with PD-1 blockade therapy. Our study demonstrates that individual mutations can be exploited, thereby opening a path to personalized immunotherapy for patients with cancer.

ObjectivesThe purpose of this study was to evaluate the prognostic relevance of temporal muscle thickness (TMT) in melanoma patients with newly diagnosed brain metastases.MethodsTMT was retrospectively assessed in 146 melanoma patients with newly diagnosed brain metastases on cranial magnetic resonance images. Chart review was used to retrieve clinical parameters, including disease-specific graded prognostic assessment (DS-GPA) and survival times.ResultsPatients with a TMT > median showed a statistically significant increase in survival time (13 months) compared to patients with a TMT < median (5 months; p < 0.001; log rank test). A Cox regression model revealed that the risk of death was increased by 27.9% with every millimeter reduction in TMT. In the multivariate analysis, TMT (HR 0.724; 95% 0.642–0.816; < 0.001) and DS-GPA (HR 1.214; 95% CI 1.023–1.439; p = 0.026) showed a statistically significant correlation with overall survival.ConclusionTMT is an independent predictor of survival in melanoma patients with brain metastases. This parameter may aid in patient selection for clinical trials or to the choice of different treatment options based on the determination of frail patient populations.

Understanding and control of the dynamic response of magnetic materials with a three-dimensional magnetization distribution is important both fundamentally and for technological applications. From a fundamental point of view, the internal magnetic structure and dynamics in bulk materials still need to be mapped1, including the dynamic properties of topological structures such as vortices2, magnetic singularities3 or skyrmion lattices4. From a technological point of view, the response of inductive materials to magnetic fields and spin-polarized currents is essential for magnetic sensors and data storage devices5. Here, we demonstrate time-resolved magnetic laminography, a pump–probe technique, which offers access to the temporal evolution of a three-dimensional magnetic microdisc with nanoscale resolution, and with a synchrotron-limited temporal resolution of 70 ps. We image the dynamic response to a 500 MHz magnetic field of the complex three-dimensional magnetization in a two-phase bulk magnet with a lateral spatial resolution of 50 nm. This is achieved with a stroboscopic measurement consisting of eight time steps evenly spaced over 2 ns. These measurements map the spatial transition between domain wall motion and the dynamics of a uniform magnetic domain that is attributed to variations in the magnetization state across the phase boundary. Our technique, which probes three-dimensional magnetic structures with temporal resolution, enables the experimental investigation of functionalities arising from dynamic phenomena in bulk and three-dimensional patterned nanomagnets6.Knowledge and control of the dynamic response in micromagnetic configurations is important both for understanding their fundamental properties and for their use in technological applications. Pump–probe magnetic laminography now unveils the evolution of the magnetization in a three-dimensional system with nanoscale resolution.

Planetary rings are observed not only around giant planets 1 , but also around small bodies such as the Centaur Chariklo 2 and the dwarf planet Haumea 3 . Up to now, all known dense rings were located close enough to their parent bodies, being inside the Roche limit, where tidal forces prevent material with reasonable densities from aggregating into a satellite. Here we report observations of an inhomogeneous ring around the trans-Neptunian body (50000) Quaoar. This trans-Neptunian object has an estimated radius 4 of 555 km and possesses a roughly 80-km satellite 5 (Weywot) that orbits at 24 Quaoar radii 6 , 7 . The detected ring orbits at 7.4 radii from the central body, which is well outside Quaoar’s classical Roche limit, thus indicating that this limit does not always determine where ring material can survive. Our local collisional simulations show that elastic collisions, based on laboratory experiments 8 , can maintain a ring far away from the body. Moreover, Quaoar’s ring orbits close to the 1/3 spin–orbit resonance 9 with Quaoar, a property shared by Chariklo’s 2 , 10 , 11 and Haumea’s 3 rings, suggesting that this resonance plays a key role in ring confinement for small bodies. The authors report observations of a dense and inhomogeneous ring at a surprisingly large distance from the trans-Neptunian body Quaoar.