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Penetrating, high‐energy synchrotron X‐rays are in strong demand, particularly for high‐pressure research in physics, chemistry and geosciences, and for materials engineering research under less extreme conditions. A new high‐energy wiggler beamline P61 has been constructed to meet this need at PETRA III in Hamburg, Germany. The first part of the paper offers an overview of the beamline front‐end components and beam characteristics. The second part describes the performance of the instrumentation and the latest developments at the P61B endstation. Particular attention is given to the unprecedented high‐energy photon flux delivered by the ten wigglers of the PETRA III storage ring and the challenges faced in harnessing this amount of flux and heat load in the beam. Furthermore, the distinctiveness of the world's first six‐ram Hall‐type large‐volume press, Aster‐15, at a synchrotron facility is described for research with synchrotron X‐rays. Additionally, detection schemes, experimental strategies and preliminary data acquired using energy‐dispersive X‐ray diffraction and radiography techniques are presented. The operation of the P61B endstation large‐volume press and optics of P61 are reviewed. The instrumentation at P61B, including the large‐volume press, detection systems and data acquisition for in situ high‐pressure experiments are described.

ObjectivesTo explore factors that influence relationship building between telehealth professionals and patients with chronic illness over a distance, from a telehealth professional's perspective.Design4 focus group interviews were conducted in June 2014. Digital recordings were transcribed verbatim and qualitative content analysis was performed using an iterative process of 3 coding rounds.Participants20 telehealth professionals.SettingA telehealth service centre in the south of Germany that provided care for 12 000 patients with chronic heart failure across Germany.ResultsNon-video telehealth technology creates an atmosphere that fosters sharing of personal information and a non-judgemental attitude. This facilitates the delivery of fair and equal healthcare. A combination of a protocol-driven service structure along with shared team and organisational values provide a basis for establishing long-term healthcare relationships. However, each contact between a telehealth professional and a patient has an uncertain outcome and requires skilful negotiation of the relationship. Although care provision was personalised, there was scope to include the patients as ‘experts on their own illness’ to a greater extent as advocated by person-centred care. Currently, provision of person-centred care is not sufficiently addressed in telehealth professional training.ConclusionsTelehealth offers a viable environment for the delivery of person-centred care for patients with long-standing disease. Current telehealth training programmes may be enhanced by teaching person-centred care skills.

Numerous cell functions are accompanied by phenotypic changes in viscoelastic properties, and measuring them can help elucidate higher level cellular functions in health and disease. We present a high-throughput, simple and low-cost microfluidic method for quantitatively measuring the elastic (storage) and viscous (loss) modulus of individual cells. Cells are suspended in a high-viscosity fluid and are pumped with high pressure through a 5.8 cm long and 200 µm wide microfluidic channel. The fluid shear stress induces large, ear ellipsoidal cell deformations. In addition, the flow profile in the channel causes the cells to rotate in a tank-treading manner. From the cell deformation and tank treading frequency, we extract the frequency-dependent viscoelastic cell properties based on a theoretical framework developed by R. Roscoe [1] that describes the deformation of a viscoelastic sphere in a viscous fluid under steady laminar flow. We confirm the accuracy of the method using atomic force microscopy-calibrated polyacrylamide beads and cells. Our measurements demonstrate that suspended cells exhibit power-law, soft glassy rheological behavior that is cell-cycle-dependent and mediated by the physical interplay between the actin filament and intermediate filament networks. Cells in the human body are viscoelastic: they have some of the properties of an elastic solid, like rubber, as well as properties of a viscous fluid, like oil. To carry out mechanical tasks – such as, migrating through tissues to heal a wound or to fight inflammation – cells need the right balance of viscosity and elasticity. Measuring these two properties can therefore help researchers to understand important cell tasks and how they are impacted by disease. However, quantifying these viscous and elastic properties is tricky, as both depend on the time-scale they are measured: when pressed slowly, cells appear soft and liquid, but they turn hard and thick when rapidly pressed. Here, Gerum et al. have developed a new system for measuring the viscosity and elasticity of individual cells that is fast, simple, and inexpensive. In this new method, cells are suspended in a specialized solution with a consistency similar to machine oil which is then pushed with high pressure through channels less than half a millimeter wide. The resulting flow of fluid shears the cells, causing them to elongate and rotate, which is captured using a fast camera that takes 500 images per second. Gerum et al. then used artificial intelligence to extract each cell’s shape and rotation speed from these images, and calculated their viscosity and elasticity based on existing theories of how viscoelastic objects behave in fluids. Gerum et al. also investigated how the elasticity and viscosity of cells changed with higher rotation frequencies, which corresponds to shorter time-scales. This revealed that while higher frequencies made the cells appear more viscous and elastic, the ratio between these two properties remained the same. This means that researchers can compare results obtained from different experimental techniques, even if the measurements were carried out at completely different frequencies or time-scales. The method developed by Gerum et al. provides a fast an inexpensive way for analyzing the viscosity and elasticity of cells. It could also be a useful tool for screening the effects of drugs, or as a diagnostic tool to detect diseases that affect the mechanical properties of cells.

In total joint arthroplasty, wear and corrosion at modular taper junctions is an issue with clinical implications, as ions and wear debris can lead to adverse tissue reactions. The quantification of the generated wear is, therefore, an important measure to judge the performance of such modular junctions. This applies to pre-clinical in vitro investigations as well as to retrospective investigations of retrieved implants. The volume of the worn material can be determined with coordinate measuring machines (CMMs), which can generally be classified as tactile and optical systems. The study aims on the comparison of a tactile with two optical CMM systems for the determination of taper wear. To do so, four taper samples—three trunnions and one bore taper—with different amounts of known volumetric wear (range 1.5 mm 3 to 8.3 mm 3 ) were fabricated. Wear volume, linear deviation and taper angle were determined with the different CMM systems. The tactile system yielded the highest deviation from the gravimetric reference values of about 0.3 mm 3 , while the optical systems exhibited deviations of about 0.1 mm 3 and 0.2 mm 3 . Clinically relevant taper wear, however, is well measurable with all investigated systems.

This study explores how researchers’ analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers’ expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each team’s workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers’ results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.

Background Hand grip strength (HGS) is a widely used functional test for the assessment of strength and functional status in patients with cancer, in particular with cancer cachexia. The aim was to prospectively evaluate the prognostic value of HGS in patients with mostly advanced cancer with and without cachexia and to establish reference values for a European‐based population. Methods In this prospective study, 333 patients with cancer (85% stage III/IV) and 65 healthy controls of similar age and sex were enrolled. None of the study participants had significant cardiovascular disease or active infection at baseline. Repetitive HGS assessment was performed using a hand dynamometer to measure the maximal HGS (kilograms). Presence of cancer cachexia was defined when patients had ≥5% weight loss within 6 months or when body mass index was <20.0 kg/m2 with ≥2% weight loss (Fearon's criteria). Cox proportional hazard analyses were performed to assess the relationship of maximal HGS to all‐cause mortality and to determine cut‐offs for HGS with the best predictive power. We also assessed associations with additional relevant clinical and functional outcome measures at baseline, including anthropometric measures, physical function (Karnofsky Performance Status and Eastern Cooperative of Oncology Group), physical activity (4‐m gait speed test and 6‐min walk test), patient‐reported outcomes (EQ‐5D‐5L and Visual Analogue Scale appetite/pain) and nutrition status (Mini Nutritional Assessment). Results The mean age was 60 ± 14 years; 163 (51%) were female, and 148 (44%) had cachexia at baseline. Patients with cancer showed 18% lower HGS than healthy controls (31.2 ± 11.9 vs. 37.9 ± 11.6 kg, P < 0.001). Patients with cancer cachexia had 16% lower HGS than those without cachexia (28.3 ± 10.1 vs. 33.6 ± 12.3 kg, P < 0.001). Patients with cancer were followed for a mean of 17 months (range 6–50), and 182 (55%) patients died during follow‐up (2‐year mortality rate 53%) (95% confidence interval 48–59%). Reduced maximal HGS was associated with increased mortality (per −5 kg; hazard ratio [HR] 1.19; 1.10–1.28; P < 0.0001; independently of age, sex, cancer stage, cancer entity and presence of cachexia). HGS was also a predictor of mortality in patients with cachexia (per −5 kg; HR 1.20; 1.08–1.33; P = 0.001) and without cachexia (per −5 kg; HR 1.18; 1.04–1.34; P = 0.010). The cut‐off for maximal HGS with the best predictive power for poor survival was <25.1 kg for females (sensitivity 54%, specificity 63%) and <40.2 kg for males (sensitivity 69%, specificity 68%). Conclusions Reduced maximal HGS was associated with higher all‐cause mortality, reduced overall functional status and decreased physical performance in patients with mostly advanced cancer. Similar results were found for patients with and without cancer cachexia.

Ex-vivo gene editing in T lymphocytes paves the way for novel concepts of immunotherapy. One of those strategies is directed at the protection of CD4+-T helper cells from HIV infection in HIV-positive individuals. To this end, we have developed and optimised a CCR5-targeting TALE nuclease, CCR5-Uco-hetTALEN, mediating high-efficiency knockout of C-C motif chemokine receptor 5 (CCR5), the HIV co-receptor essential during initial infection. Clinical translation of the knockout approach requires up-scaling of the manufacturing process to clinically relevant cell numbers in accordance with good manufacturing practice (GMP). Here we present a GMP-compatible mRNA electroporation protocol for the automated production of CCR5-edited CD4+-T cells in the closed CliniMACS Prodigy system. The automated process reliably produced high amounts of CCR5-edited CD4+-T cells (>1.5 × 109 cells with >60% CCR5 editing) within 12 days. Of note, about 40% of total large-scale produced cells showed a biallelic CCR5 editing, and between 25 and 42% of produced cells had a central memory T-cell phenotype. In conclusion, transfection of primary T cells with CCR5-Uco-hetTALEN mRNA is readily scalable for GMP-compatible production and hence suitable for application in HIV gene therapy.

Objectives Conventional dental implants inserted in the molar region of the maxilla will reach into the sinus maxillaris when alveolar ridge height is limited. When surgery is performed without prior augmentation of the sinus floor, primary stability of the implant is important for successful osseointegration. This study aimed at identifying the impact of bone quality and quantity at the implantation site on primary implant stability of a simulated bicortical placement. Materials and methods In our in vitro measurements, bone mineral density, total bone thickness and overall cortical bone thickness were assessed by micro-computed tomography (μCT) of pig scapulae, which resembled well the bicortical situation found in human patients. Dental implants were inserted, and micromotion between bone and implant was measured while loading the implant with an axial torque. Results The main findings were that primary implant stability did not depend on total bone thickness but tended to increase with either increasing bone mineral density or overall cortical bone thickness. Clinical relevance Limited bone height in the maxilla is a major problem when planning dental implants. To overcome this problem, several approaches, e.g. external or internal sinus floor elevation, have been established. When planning the insertion of a dental implant an important aspect is the primary stability which can be expected. With other factors, the dimensions of the cortical bone might be relevant in this context. It would, therefore, be helpful to define the minimum thickness of cortical bone required to achieve sufficient primary stability, thus avoiding additional surgical intervention.

The efficient optimization method for locally Lipschitz continuous multiobjective optimization problems from Gebken and Peitz (J Optim Theory Appl 188:696–723, 2021) is extended from finite-dimensional problems to general Hilbert spaces. The method iteratively computes Pareto critical points, where in each iteration, an approximation of the Clarke subdifferential is computed in an efficient manner and then used to compute a common descent direction for all objective functions. To prove convergence, we present some new optimality results for nonsmooth multiobjective optimization problems in Hilbert spaces. Using these, we can show that every accumulation point of the sequence generated by our algorithm is Pareto critical under common assumptions. Computational efficiency for finding Pareto critical points is numerically demonstrated for multiobjective optimal control of an obstacle problem.