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The ability to write, hence to preserve and share arbitrary words and thoughts, was one of the most important breakthroughs in the history of mankind. It laid the technological basis for what we perceive today as culture, science and, in good part, economy. Nonetheless, writing can encompass much more than just words, and this is an integral, but often overlooked part of it. Until very recently, writing was necessarily bound to the physical medium on which it was written or into which it was inscribed. The physicality of the medium interacted with and often enhanced the purely textual message. These features, which go beyond the encoding of words, are the secondary characteristics of writing systems. They include, but are not limited to typography, and often serve, consciously or not, the transmission of additional messages beyond the purely textual content. If the study of writing itself is still largely in its infancy, this is even more true for the study of secondary characteristics, which is an integral part of grammatology. Beginning with a taxonomy of these secondary characteristics, this article looks in more detail at two non-typographical characteristics, namely ordering and punctuation. This short sketch of a cultural history of ordering and punctuation begins with the role of ordering in the initial invention of writing over its use across the millennia. It ends with the contemporary use of special punctuation marks to encode emotions.

Objective: While guidelines encourage individualized discussions of the risks and benefits of antiseizure medication (ASM) withdrawal after a period of seizure-freedom, no formal methods exist for assessing patient preferences. We report the initial development of a rapid patient preferences screener., Methods: We conducted a mixed-methods study of adults who were ≥1 year seizure-free and seen for epilepsy across three institutions. We reviewed existing questionnaires and adapted three questions measuring core constructs influencing ASM decisions - views about ASMs, driving restrictions, and seizures. We added one additional "global" question, for 4 total questions. Participants rated question clarity and utility from 1 (low) to 7 (high)., Results: Of 32 participants, the median patient age was 46 (interquartile range [IQR] 33-56), with a median 3 years since their last seizure (IQR 2-11). Median responses were: 2 (IQR 1-5) for being bothered by ASMs, 2 (IQR 1-6) for feeling that a driving restriction would be disruptive, and 5 (IQR 4-7) for feeling that another seizure would be serious. Respondents tended to disagree that ASMs are doing more harm than good (median 1, IQR 1-2). Participants rated question clarity (median 6, IQR 6-7) and utility (median 7, IQR 6-7) highly., Conclusions: We report the initial development of a pre-visit rapid screener of patient preferences pertinent to ASM withdrawal in well-controlled epilepsy. Patients endorsed the utility of such a screener and provided guidance to improve items. We hope that this work will ultimately improve shared decision-making., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper. Dr Terman was recently supported by an American Epilepsy Society Research and Training Fellowship for Clinicians. He is now supported by the National Institutes of Health K23 AG081463. He has been a paid consultant for Jazz Pharmaceuticals and is currently a paid consultant for Xenon Pharmaceuticals. Dr Hill is funded by NIH K23NS126495. Other authors report no relevant funding., (Copyright © 2024 Elsevier Inc. All rights reserved.)

It is widely known that freezing breaks soft, wet materials. However, the mechanism underlying this damage is still not clear. To understand this process, we freeze model, brittle hydrogel samples, while observing the growth of ice-filled cracks that break these apart. We show that damage is not caused by the expansion of water upon freezing or the growth of ice-filled cavities in the hydrogel that exert pressure on the surrounding material. Instead, local ice growth dehydrates the adjacent hydrogel, leading to drying-induced fracture. This dehydration is driven by the process of cryosuction, whereby undercooled ice sucks nearby water toward itself, feeding ice growth. Our results highlight the strong analogy between freezing damage and desiccation cracking, which we anticipate being useful for developing an understanding of both topics. Our results should also give useful insights into a wide range of freezing processes, including cryopreservation, food science, and frost heave.

Objectives: This study aimed to investigate whether adding tissue samples directly into thioglycolate (TG) broth yielded a greater number of anaerobic organisms than freshly sampled tissue in suspected hip and knee prosthetic joint infections (PJIs)., Patients and Methods: Between January 2017 and December 2020, a total of 90 patients (46 males, 44 females; median age: 71.7 years; range, 50.8 and 87.8 years) who underwent revision hip or knee arthroplasty were included. Intraoperative samples were taken, with five placed in TG broth and five in standard containers (PC) with subsequent aerobic and anaerobic culturing conducted. Demographic and baseline data of the patients were recorded. The primary outcome was positive bacterial growth from a PJI specimen inoculated directly into TG broth at the time of collection or standard PJI specimen processing. Secondary outcomes investigated were the presence of Cutibacterium acnes (C. acnes) and the curative success of revision procedure., Results: A total of 900 samples (450 PC and 450 TG) were taken from 90 revision arthroplasty patients (47 knees and 43 hips). There was no statistically significant difference in the number of positive bacterial growth samples between TG broth and standard processing (p=0.742). This was consistent with subgroup analysis analyzing C. acnes (p=0.666)., Conclusion: In hip and knee arthroplasty, there is no benefit in substituting or adding TG broth as a culture medium to better identify both general bacterial species and C. acnes infections specifically. However, the use of TG may be useful in confirming a true positive result for infection.

The idea of using ultrashort X-ray pulses to obtain images of single proteins frozen in time has fascinated and inspired many. It was one of the arguments for building X-ray free-electron lasers. According to theory, the extremely intense pulses provide sufficient signal to dispense with using crystals as an amplifier, and the ultrashort pulse duration permits capturing the diffraction data before the sample inevitably explodes. This was first demonstrated on biological samples a decade ago on the giant mimivirus. Since then, a large collaboration has been pushing the limit of the smallest sample that can be imaged. The ability to capture snapshots on the timescale of atomic vibrations, while keeping the sample at room temperature, may allow probing the entire conformational phase space of macromolecules. Here we show the first observation of an X-ray diffraction pattern from a single protein, that of Escherichia coli GroEL which at 14 nm in diameter is the smallest biological sample ever imaged by X-rays, and demonstrate that the concept of diffraction before destruction extends to single proteins. From the pattern, it is possible to determine the approximate orientation of the protein. Our experiment demonstrates the feasibility of ultrafast imaging of single proteins, opening the way to single-molecule time-resolved studies on the femtosecond timescale., (© 2024. The Author(s).)

Background: Fretting corrosion at modular junctions contributes to arthroplasty failure. Currently, no evidence-based guidelines are available regarding the acceptable level of trunnion corrosion that can occur in vivo . We aimed to examine the relationship between trunnion corrosion and risk of re-revision to assist surgeons with intraoperative decision making., Method: Grading by 3 independent examiners of revised and re-revised head components was performed using a modified Goldberg corrosion scale. Samples were separated into low-grade (LG) and high-grade (HG) corrosion. Mechanical testing determined the relationship between corrosion severity and pull-off strength at the head-stem junction., Results: 529 retrieved femoral heads were analysed. A positive association was detected between males and HG corrosion (OR 2.07; 95% CI, 1.45-2.94; p  < 0.001). No difference between the survivorship of LG and HG heads was detected ( p -value = 0.247). In the re-revised sample, the first implant had a time in situ that was on average 7.97 years longer (95% CI, 5.4-10.6) than that of the subsequent re-revised femoral head. Severe corrosion on the first head was associated with a 37.5 (95% CI, 4.00-1944) fold increase of HG on the subsequent head ( p  < 0.001). Femoral disassembly force had a positive correlation with stem taper corrosion grade ( p  = 0.001)., Conclusions: A well-fixed stem with corrosion may remain in situ ., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MK: received institutional support from: Zimmer Biomet.All other authors declare that there is no conflict of interest.

Superfluid helium nanodroplets are an ideal environment for the formation of metastable, self-organized dopant nanostructures. However, the presence of vortices often hinders their formation. Here, we demonstrate the generation of vortex-free helium nanodroplets and explore the size range in which they can be produced. From x-ray diffraction images of xenon-doped droplets, we identify that single compact structures, assigned to vortex-free aggregation, prevail up to 10^{8} atoms per droplet. This finding builds the basis for exploring the assembly of far-from-equilibrium nanostructures at low temperatures.

Aim: The ideal route of tranexamic acid (TXA) administration in total hip arthroplasty (THA) or total knee arthroplasty (TKA) remains controversial. This study aims to identify the optima route of TXA administration in THA or TKA., Methods: PUBMED, EMBASE, MEDLINE and CENTRAL database were systematically searched until 4 August 2021 for randomised studies that compared intravenous (IV) or intra-articular (IA) administration of TXA in THA or TKA., Results: Sixty-seven studies enrolling 8335 patients (IA: 4162; IV: 4173) were eligible for quantitative and qualitative analysis. Comparable results were demonstrated in the incidence of venous thromboembolisation (OR:0.96, p = 0.84), total blood loss (MD: - 9.05, p = 0.36), drain output (MD: - 7.36, p = 0.54), hidden blood loss (MD: - 6.85, p = 0.47), postoperative haemoglobin level (MD: 0.01, p = 0.91), haemoglobin drop (MD: - 0.10, p = 0.22), blood transfusion rate (OR: 0.99, p = 0.87), total adverse events (OR: 1.12, p = 0.28), postoperative range of motion (MD: 1.08, p = 0.36), postoperative VAS pain score (MD: 0.13, p = 0.24) and postoperative D-dimer level (MD: 0.61, p = 0.64). IV route of TXA administration was associated with significantly longer length of hospital stay compared to IA route of administration (MD: - 0.22, p = 0.01)., Conclusion: In this meta-analysis, both IV and IA route of TXA administration were equally effective in managing blood loss and postoperative outcomes in lower limb joints arthroplasty., Level of Evidence: Level 1. PROSPERO Registration CRD42021271355., (© 2022. Crown.)

The advent of X-ray free-electron lasers (XFELs) has revolutionized fundamental science, from atomic to condensed matter physics, from chemistry to biology, giving researchers access to X-rays with unprecedented brightness, coherence and pulse duration. All XFEL facilities built until recently provided X-ray pulses at a relatively low repetition rate, with limited data statistics. Here, results from the first megahertz-repetition-rate X-ray scattering experiments at the Spectroscopy and Coherent Scattering (SCS) instrument of the European XFEL are presented. The experimental capabilities that the SCS instrument offers, resulting from the operation at megahertz repetition rates and the availability of the novel DSSC 2D imaging detector, are illustrated. Time-resolved magnetic X-ray scattering and holographic imaging experiments in solid state samples were chosen as representative, providing an ideal test-bed for operation at megahertz rates. Our results are relevant and applicable to any other non-destructive XFEL experiments in the soft X-ray range., (open access.)

Objectives: To investigate the mechanical properties of cephalomedullary nailing of intertrochanteric OTA/AO 31-A3.1 (reverse oblique) fractures and to test the hypothesis that anatomical reduction and augmentation with cerclage wire produces a more stable construct., Methods: A standardized fracture model in composite saw bone was created to stimulate an intertrochaneric 31-A3.1 fracture, using a 3D printed cutting guide. Simulated osteosynthesis was performed with 12 femurs divided into anatomically reduced and varus malreduced groups. Each femur was tested with and without cerclage wire augmentation. All femurs were fixed with a 215 mm, 130 degree, 11.5 mm nail. An Instron 8874 biaxial materials testing machine was used to assess the axial stiffness. Cyclic loading consisted of 5000 cycles of sinusoidal combined axial-torsion loading at 3 Hz. Axial load was 100 N to 2000 N and torsion -4.5 Nm to +4.5 Nm. Stiffness was measured before and after cyclic loading., Results: Reduced constructs were stiffer than residual varus constructs. The mean overall fracture stiffness was 508.7 N/mm for reduced constructs and 379.2 N/mm for varus constructs. Removing the cables significantly decreased the fracture stiffness for both constructs (mean difference 60.0 N/mm, 95% CI 7.7-112.3, P  = .032)., Conclusions: Anatomical reduction has a dominant effect on facture stiffness. Anatomically reduced fractures are stiffer than varus malreduced fractures. A cerclage wire further improves construct stiffness if anatomical reduction is achieved. Cerclage wiring is less effective if anatomical reduction is not achieved., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)