Investigating the existence of an osmotic barrier between xylem fibres and vessels in sugar maple (Acer saccharum) using microCT.

Sugar maples (Acer saccharum Marshall) develop elevated stem pressures in springtime through the compression and expansion of gas bubbles present within xylem fibres. The stability of this gas within the fibres is hypothesised to be due to the elevated sugar concentration of maple sap and the presence of an osmotic barrier between fibres and vessels. Without this osmotic barrier gas bubbles are predicted to dissolve rapidly. In this work we investigated the existence of this osmotic barrier. We quantified the fraction of the xylem occupied by gas-filled fibres using synchrotron based microCT. After imaging fresh stem segments we perfused them with either a 2% sucrose solution or water, imaging again following perfusion. In this way we directly observed how total gas present in the fibres changed when an osmotic pressure difference should be present, with the 2% sucrose solution, and when it is absent, with the water. Following a first round of perfusion we perfused stem segments with the other perfusate, repeating this multiple times to observe how switching perfusates affected gas-filled fibres. We found that perfusing stem segments with water resulted in a significant reduction in the xylem fibre gas, but perfusing stem segments with a sucrose solution did not significantly reduce the gas in the fibres. These results support the hypothesis that an osmotic barrier exists between fibres and vessels.

Avoided metallicity in a hole-doped Mott insulator on a triangular lattice.

Doping of a Mott insulator gives rise to a wide variety of exotic emergent states, from high-temperature superconductivity to charge, spin, and orbital orders. The physics underpinning their evolution is, however, poorly understood. A major challenge is the chemical complexity associated with traditional routes to doping. Here, we study the Mott insulating CrO2 layer of the delafossite PdCrO2, where an intrinsic polar catastrophe provides a clean route to doping of the surface. From scanning tunnelling microscopy and angle-resolved photoemission, we find that the surface stays insulating accompanied by a short-range ordered state. From density functional theory, we demonstrate how the formation of charge disproportionation results in an insulating ground state of the surface that is disparate from the hidden Mott insulator in the bulk. We demonstrate that voltage pulses induce local modifications to this state which relax over tens of minutes, pointing to a glassy nature of the charge order.

Chemical Trends of the Bulk and Surface Termination-Dependent Electronic Structure of Metal-Intercalated Transition Metal Dichalcogenides.

The addition of metal intercalants into the van der Waals gaps of transition metal dichalcogenides has shown great promise as a method for controlling their functional properties. For example, chiral helimagnetic states, current-induced magnetization switching, and a giant valley-Zeeman effect have all been demonstrated, generating significant renewed interest in this materials family. Here, we present a combined photoemission and density-functional theory study of three such compounds: , , and , to investigate chemical trends of the intercalant species on their bulk and surface electronic structure. Our resonant photoemission measurements indicate increased hybridization with the itinerant NbS2-derived conduction states with increasing atomic number of the intercalant, leading to pronounced mixing of the nominally localized intercalant states at the Fermi level. Using spatially and angle-resolved photoemission spectroscopy, we show how this impacts surface-termination-dependent charge transfers and leads to the formation of new dispersive states of mixed intercalant-Nb character at the Fermi level for the intercalant-terminated surfaces. This provides an explanation for the origin of anomalous states previously reported in this family of compounds and paves the way for tuning the nature of the magnetic interactions in these systems via control of the hybridization of the magnetic ions with the itinerant states.

A DNA condensation code for linker histones.

Linker histones play an essential role in chromatin packaging by facilitating compaction of the 11-nm fiber of nucleosomal "beads on a string." The result is a heterogeneous condensed state with local properties that range from dynamic, irregular, and liquid-like to stable and regular structures (the 30-nm fiber), which in turn impact chromatin-dependent activities at a fundamental level. The properties of the condensed state depend on the type of linker histone, particularly on the highly disordered C-terminal tail, which is the most variable region of the protein, both between species, and within the various subtypes and cell-type specific variants of a given organism. We have developed an in vitro model system comprising linker histone tail and linker DNA, which although very minimal, displays surprisingly complex behavior, and is sufficient to model the known states of linker histone-condensed chromatin: disordered "fuzzy" complexes ("open" chromatin), dense liquid-like assemblies (dynamic condensates), and higher-order structures (organized 30-nm fibers). A crucial advantage of such a simple model is that it allows the study of the various condensed states by NMR, circular dichroism, and scattering methods. Moreover, it allows capture of the thermodynamics underpinning the transitions between states through calorimetry. We have leveraged this to rationalize the distinct condensing properties of linker histone subtypes and variants across species that are encoded by the amino acid content of their C-terminal tails. Three properties emerge as key to defining the condensed state: charge density, lysine/arginine ratio, and proline-free regions, and we evaluate each separately using a strategic mutagenesis approach.

Fermi Surface Nesting Driving the RKKY Interaction in the Centrosymmetric Skyrmion Magnet Gd_{2}PdSi_{3}.

The magnetic skyrmions generated in a centrosymmetric crystal were recently first discovered in Gd_{2}PdSi_{3}. In light of this, we observe the electronic structure by angle-resolved photoemission spectroscopy and unveil its direct relationship with the magnetism in this compound. The Fermi surface and band dispersions are demonstrated to have a good agreement with the density functional theory calculations carried out with careful consideration of the crystal superstructure. Most importantly, we find that the three-dimensional Fermi surface has extended nesting which matches well the q vector of the magnetic order detected by recent scattering measurements. The consistency we find among angle-resolved photoemission spectroscopy, density functional theory, and the scattering measurements suggests the Ruderman-Kittel-Kasuya-Yosida interaction involving itinerant electrons to be the formation mechanism of skyrmions in Gd_{2}PdSi_{3}.

Seniority of Surgeon in Chronic Subdural Hematoma Recurrence: A Systematic Review and Meta-analysis.

Chronic subdural hematoma (CSDH) is increasingly common, particularly in the older and multimorbid population. Surgical proficiency in management is required in the early years of U.K. neurosurgical training with most cases performed by nonconsultant-grade surgeons. The aim of this systematic review was to examine the effect of surgeon seniority on recurrence for patients with CSDH. Full-text articles comparing surgical treatment for CSDH with a "senior" (consultant/attending level) or "junior" (resident/registrar or similar) lead surgeon were identified. MEDLine and EMBASE databases were searched. The primary outcome of this study was recurrence. Secondary outcomes included postoperative complications and mortality rate. A random effects meta-analysis was performed. The risk of bias was assessed using the National Institute of Health risk of bias toolkit. Five studies were included in the final analysis (n = 941 total patients). Individually, no study identified a significant difference in recurrence rate and postoperative complications between senior and junior neurosurgeons. On meta-analysis, junior-led evacuations had lower recurrence rates on pooled univariable analysis (12.0% vs. 17.9% [odds ratio 0.48, 95% confidence interval 0.29-0.78, I2 = 0%]) (3 studies). Seniority of surgeon was not associated with increased rates of recurrence patients undergoing CSDH surgery. Complexity of operation may be a confounding factor in observed lower recurrence rates with more junior operators.

Weyl spin-momentum locking in a chiral topological semimetal.

Spin-orbit coupling in noncentrosymmetric crystals leads to spin-momentum locking - a directional relationship between an electron's spin angular momentum and its linear momentum. Isotropic orthogonal Rashba spin-momentum locking has been studied for decades, while its counterpart, isotropic parallel Weyl spin-momentum locking has remained elusive in experiments. Theory predicts that Weyl spin-momentum locking can only be realized in structurally chiral cubic crystals in the vicinity of Kramers-Weyl or multifold fermions. Here, we use spin- and angle-resolved photoemission spectroscopy to evidence Weyl spin-momentum locking of multifold fermions in the chiral topological semimetal PtGa. We find that the electron spin of the Fermi arc surface states is orthogonal to their Fermi surface contour for momenta close to the projection of the bulk multifold fermion at the Γ point, which is consistent with Weyl spin-momentum locking of the latter. The direct measurement of the bulk spin texture of the multifold fermion at the R point also displays Weyl spin-momentum locking. The discovery of Weyl spin-momentum locking may lead to energy-efficient memory devices and Josephson diodes based on chiral topological semimetals.

[Chemsex - drug use primarily orientated around a sexual experience - Patients that fall through the gaps].

INTRODUCTION: Drug use in a sexualised context provides unique challenges both in specialised clinics (psychiatric and sexual health clinics) as well as general practice. Layered onto this leads some inequalities in health care to poorer outcomes in specific groups. This article aims to provide evidence based harm reduction strategies that can easily be applied in primary care to reduce complications, identify those at higher risk and deploy appropriate treatments.

Impact of antithrombotic agents on outcomes in patients requiring surgery for chronic subdural haematoma: a systematic review and meta-analysis.

A chronic subdural haematoma (CSDH) is a collection of aged blood between the dura and the brain, typically treated with surgical evacuation. Many patients with CSDH have comorbidities requiring the use of antithrombotic medications. The optimal management of these medications in the context of CSDH remains unknown, as the risk of recurrence must be carefully weighed against the risk of vaso-occlusive events. To better understand these risks and inform the development of clinical practice guidelines, we conducted a systematic review and meta-analysis. A systematic review was conducted in accordance with the PRISMA guidelines, searching Medline and Embase databases. The study was registered with PROSPERO (CRD42023397061). A total of 44 studies were included, encompassing 1 prospective cohort study and 43 retrospective cohort studies. Pooled odds ratios (ORs) were calculated for CSDH recurrence and vaso-occlusive events in patients taking anticoagulant or antiplatelet medications compared to patients not receiving antithrombotic therapy. GRADE was used to assess the quality of evidence. In patients on anticoagulant therapy at CSDH diagnosis, the pooled OR for CSDH recurrence was 1.41 (95% CI 1.11 to 1.79; I2 = 28%). For patients on antiplatelet therapy, the pooled OR was 1.31 (95% CI 1.08 to 1.58; I2 = 32%). Patients taking antithrombotic medications had a significantly higher risk of vaso-occlusive events, with a pooled OR of 3.74 (95% CI 2.12 to 6.60; I2 = 0%). There was insufficient evidence to assess the impact of time to recommence antithrombotic medication on CSDH outcomes. We found that baseline antithrombotic use is associated with the risk of CSDH recurrence and vaso-occlusive events following surgical evacuation. The evidence base is of low quality, and decisions regarding antithrombotic therapy should be individualised for each patient. Further high-quality, prospective studies or registry-based designs are needed to better inform clinical decision-making and establish evidence-based guidelines.

Characterization of cardiac fibroblast-extracellular matrix crosstalk across developmental ages provides insight into age-related changes in cardiac repair.

Heart failure afflicts an estimated 6.5 million people in the United States, driven largely by incidents of coronary heart disease (CHD). CHD leads to heart failure due to the inability of adult myocardial tissue to regenerate after myocardial infarction (MI). Instead, immune cells and resident cardiac fibroblasts (CFs), the cells responsible for the maintenance of the cardiac extracellular matrix (cECM), drive an inflammatory wound healing response, which leads to fibrotic scar tissue. However, fibrosis is reduced in fetal and early (<1-week-old) neonatal mammals, which exhibit a transient capability for regenerative tissue remodeling. Recent work by our laboratory and others suggests this is in part due to compositional differences in the cECM and functional differences in CFs with respect to developmental age. Specifically, fetal cECM and CFs appear to mitigate functional loss in MI models and engineered cardiac tissues, compared to adult CFs and cECM. We conducted 2D studies of CFs on solubilized fetal and adult cECM to investigate whether these age-specific functional differences are synergistic with respect to their impact on CF phenotype and, therefore, cardiac wound healing. We found that the CF migration rate and stiffness vary with respect to cell and cECM developmental age and that CF transition to a fibrotic phenotype can be partially attenuated in the fetal cECM. However, this effect was not observed when cells were treated with cytokine TGF-ß1, suggesting that inflammatory signaling factors are the dominant driver of the fibroblast phenotype. This information may be valuable for targeted therapies aimed at modifying the CF wound healing response and is broadly applicable to age-related studies of cardiac remodeling.

Promoting mental health in esports.

There is growing recognition of the demands and health challenges experienced by esports athletes. The purpose of this perspective paper is to draw specific attention to the mental health of competitive gamers and spur on both future research and applied initiatives focussing on this important but under-addressed topic. We will briefly discuss the prevalence of mental health concerns, domain-specific stressors, and the need for comprehensive mental health support systems tailored to the esports context. It is our hope that, with this perspective paper, we can help set a new research agenda addressing mental health in esports.

Adaptation of an rVSV Ebola vaccine purification process for rapid development of a viral vaccine candidate for SARS-CoV-2.

During the COVID-19 pandemic, long development timelines typically associated with vaccines were challenged. The urgent need for a vaccine provided a strong driver to reevaluate existing vaccine development approaches. Innovative approaches to regulatory approval were realized, including the use of platform-based technology. In collaboration with the International AIDS Vaccine Initiative, Inc. (IAVI), Merck & Co., Inc., Rahway, NJ, USA rapidly advanced an investigational SARS-CoV-2 vaccine based on the recombinant vesicular stomatitis virus (rVSV) platform used for the Ebola vaccine ERVEBO (rVSV∆G-ZEBOV-GP). An rVSV∆G-SARS-CoV-2 vaccine candidate was generated using the SARS-CoV-2 spike protein to replace the VSV G protein. The purification process development for this vaccine candidate was detailed in this paper. Areas were highlighted where the ERVEBO platform process was successfully adopted and where additional measures were needed for the SARS-CoV-2 vaccine candidate. These included: (i) endonuclease addition directly into the bioreactor prior to harvest, (ii) inclusion of a core-shell chromatography step for improved purification, and (iii) incorporation of a terminal, sterile filtration step to eliminate the need for aseptic, closed processing. High infectious virus titers were achieved in Phase 3 clinical drug substance (>108 PFU mL-1 ), and process consistency was demonstrated across four large scale batches that were completed in 6 months from clone selection.

Controlling the Charge Density Wave Transition in Single-Layer TiTe2xSe2(1-x) Alloys by Band Gap Engineering.

Closing the band gap of a semiconductor into a semimetallic state gives a powerful potential route to tune the electronic energy gains that drive collective phases like charge density waves (CDWs) and excitonic insulator states. We explore this approach for the controversial CDW material monolayer (ML) TiSe2 by engineering its narrow band gap to the semimetallic limit of ML-TiTe2. Using molecular beam epitaxy, we demonstrate the growth of ML-TiTe2xSe2(1-x) alloys across the entire compositional range and unveil how the (2 × 2) CDW instability evolves through the normal state semiconductor-semimetal transition via in situ angle-resolved photoemission spectroscopy. Through model electronic structure calculations, we identify how this tunes the relative strength of excitonic and Peierls-like coupling, demonstrating band gap engineering as a powerful method for controlling the microscopic mechanisms underpinning the formation of collective states in two-dimensional materials.

Quantitative examination of the anatomy of the juvenile sugar maple xylem.

New methodologies have enabled viable sap yields from juvenile sugar maple trees. To further improve yields, a better understanding of sap exudation is required. To achieve this, the anatomy of the xylem must first be fully characterised. We examine juvenile maple saplings using light optical microscopy (LOM) and scanning electron microscopy (SEM), looking at sections cut along differing orientations as well as macerations. From this we measure various cell parameters. We find diameter and length of vessel elements to be 28 ± 8 µm and 200 ± 50 µm, for fibre cells 8 ± 3 µm and 400 ± 100 µm, and for ray parenchyma cells 8 ± 2 µm and 50 ± 20 µm. We also examine pitting present on different cell types. On vessel elements we observe elliptical bordered pits connecting to other vessel elements (with major axis of 2.1 ± 0.7 µm and minor 1.3 ± 0.3 µm) and pits connecting to ray parenchyma (with major axis of 4 ± 2 µm and minor 2.0 ± 0.7 µm). We observe two distinct pit sizes on fibres with circular pits 0.7 ± 0.2 µm in diameter and ellipsoidal pits 1.6 ± 0.4 µm by 1.0 ± 0.3 µm. We do not observe distinct pitting patterns on different fibre types. The various cell and pit measurements obtained generally agree with the limited data available for mature trees, with the exception of vessel element and fibre length, both of which were significantly smaller than reported values.

Characterizing the regulatory Fas (CD95) epitope critical for agonist antibody targeting and CAR-T bystander function in ovarian cancer.

Receptor clustering is the most critical step to activate extrinsic apoptosis by death receptors belonging to the TNF superfamily. Although clinically unsuccessful, using agonist antibodies, the death receptors-5 remains extensively studied from a cancer therapeutics perspective. However, despite its regulatory role and elevated function in ovarian and other solid tumors, another tumor-enriched death receptor called Fas (CD95) remained undervalued in cancer immunotherapy until recently, when its role in off-target tumor killing by CAR-T therapies was imperative. By comprehensively analyzing structure studies in the context of the binding epitope of FasL and various preclinical Fas agonist antibodies, we characterize a highly significant patch of positively charged residue epitope (PPCR) in its cysteine-rich domain 2 of Fas. PPCR engagement is indispensable for superior Fas agonist signaling and CAR-T bystander function in ovarian tumor models. A single-point mutation in FasL or Fas that interferes with the PPCR engagement inhibited apoptotic signaling in tumor cells and T cells. Furthermore, considering that clinical and immunological features of the autoimmune lymphoproliferative syndrome (ALPS) are directly attributed to homozygous mutations in FasL, we reveal differential mechanistic details of FasL/Fas clustering at the PPCR interface compared to described ALPS mutations. As Fas-mediated bystander killing remains vital to the success of CAR-T therapies in tumors, our findings highlight the therapeutic analytical design for potentially effective Fas-targeting strategies using death agonism to improve cancer immunotherapy in ovarian and other solid tumors.

Colorectal adenomatous and serrated polyps in rural South Australia: who, why, what and where?

BACKGROUNDS: The adenoma-carcinoma and serrated pathways offer a window of opportunity for the removal of pre-malignant polyps and prevention of colorectal cancer (CRC) through the use of colonoscopy. The aim of this study was to investigate variation in polyp incidence in different age groups, gender and indications for undertaking colonoscopy. We also address histological types of polyps found and where in the bowel they are located. METHODS: This study is based on the colonoscopy data collected prospectively over a one-year period in multiple South Australian rural centres, 24 general surgeons contributed to this study. All histopathology results were subsequently entered into the dataset. RESULTS: A total of 3497 colonoscopies were performed, with a total of 2221 adenomatous and serrated polyps removed. Both serrated and adenomatous polyps were more common in the distal colon. Patients of male gender, aged 70 years and over and with an indication of polyp surveillance had higher adenoma and serrated polyp detection rates (ADR and SPDR). Patients aged 40-49 years old who underwent colonoscopy for positive faecal occult blood had an ADR and SPDR of 25.0% and 6.3%, respectively. CONCLUSIONS: This study has shown variation in ADR and SPDR depending on age, gender and indication for colonoscopy. This variation will help further develop key performance indicators in colonoscopy. The high ADR and SPDR in patients aged 40-49 years old whom underwent colonoscopy for positive faecal occult blood may support lowering the age of commencement of CRC screening in Australia.

A Novel Perivesical Fat Rotational Flap as an Alternative to Omental Interposition in Challenging Urological Reconstruction.

OBJECTIVE: To introduce the application of the perivesical fat rotational flap as a substitute for omental interposition during several complex urologic reconstruction. We highlight our technique using a case of salvage prostatectomy after initial high-intensity focused ultrasound for recurrent high-risk prostate cancer requiring future adjuvant radiation treatment. We have also successfully used this technique in the management of recurrent vesicovaginal, colovesical, rectourethral fistulas, and postradiation salvage prostatectomy setting. MATERIALS AND METHODS: Our first patient underwent salvage radical prostatectomy after developing high-risk localized prostate cancer after initial high-intensity focused ultrasound. The prostate was radically resected after stepwise posterior and anterior dissections. A flap of perivesical fat with a wide-based pedicle overlying the bladder dome was developed until it was rotated, positioned, and tethered overlying the anterior rectal wall in a tension-free manner. This perivesical fat interposition may have protected a radiated anterior rectal wall from future complications. In the second case, a recurrent vesicovaginal fistula that persisted for 2years postabdominal hysterectomy was repaired using the robotic approach. After fistula excision, layer closure, and perivesical flap interposition, successful repair was achieved. The third patient, who had a history of colon cancer managed with partial colectomy and radiation, developed a recurrent colovesical fistula, which was successfully repaired. Postrepair, a perivesical flap was developed and secured over the site. RESULTS: In the immediate postoperative follow-up period, there were no surgical complications. Long-term follow-up ranges from 1month to 3years without evidence of complication. CONCLUSION: In cases where omentum interposition is not feasible, our novel technique of a perivesical fat flap is a successful alternative for complex reconstruction.

Comparison of robotic-assisted laparoscopic radical prostatectomy: SP versus XI, a single surgeon experience.

Currently, there is a paucity of data regarding Single Port (SP) robotic-assisted laparoscopic prostatectomy (RALP). Our objective was to compare our single-institution single-surgeon SP RALP experience to our XI RALP experience with regard to patient selection, perioperative data, and outcomes. Patients who underwent prostatectomy at our institution between August 2019 and April 2021 were selected for analysis. All patients had biopsy confirmed prostate cancer. All surgeries were performed by one urologist at our institution to limit inter-surgeon variability. Demographic and clinical information were extracted from the medical record in standardized fashion. All documented classifications were graded using the Clavien-Dindo classification system. Patients with previous prostate cancer therapies were excluded. Categorical variables were compared using Chi-square or Fisher's exact test where appropriate. Continuous variables were compared using t tests or Wilcoxon rank sum tests where appropriate. Complete records were available for 208 patients. Of the total patient population 127 (61.1%) underwent SP prostatectomy compared to 81 (38.9%) underwent XI prostatectomy. There was no significant difference between the two cohorts in terms of mean age (65 vs. 66 years; p = 0.60), BMI (29.2 vs. 30.1; p = 0.22), preop ASA score ≥ 3 (68.5% vs. 64.2%; p = 0.52), or preop PSA (7.1 vs. 7.4, p = 0.94). There no difference in procedure time for SP prostatectomy (170 vs. 168 min, p = 0.035), estimated blood loss (100 vs. 100 mL; p = 0.14), or average length of stay (1 vs. 1 days; p = 0.22). There was a significant difference in Gleason grade group between the two cohorts with patients undergoing XI RALRP more likely to have higher stage disease (p = 0.025) and a trend towards higher D'Amico risk scores in the XI group (p = 0.053). There was no difference in rate of positive surgical margins (29.9% vs. 29.6%; p = 0.96). There was no difference in the distribution of complications between the two groups (p = 0.99) with 89% of patients having no complication. There was no difference in the number of lymph nodes removed by modality (p = 0.94). To date, this study represents one of the largest cohorts of patients who underwent SP RALP. Importantly, it is among the first studies comparing perioperative variables between the SP and XI platforms. As surgeons become more facile with the SP system there appear to minimal differences in patient factors, perioperative results, or outcomes between the platforms. These findings provide evidence that surgeons who are competent on the XI platform can confidently perform SP RALPs through a single incision without compromising outcomes.

Personalising monitoring for chemotherapy patients through predicting deterioration in renal and hepatic function.

BACKGROUND: In those receiving chemotherapy, renal and hepatic dysfunction can increase the risk of toxicity and should therefore be monitored. We aimed to develop a machine learning model to identify those patients that need closer monitoring, enabling a safer and more efficient service. METHODS: We used retrospective data from a large academic hospital, for patients treated with chemotherapy for breast cancer, colorectal cancer and diffuse-large B-cell lymphoma, to train and validate a Multi-Layer Perceptrons (MLP) model to predict the outcomes of unacceptable rises in bilirubin or creatinine. To assess the performance of the model, validation was performed using patient data from a separate, independent hospital using the same variables. Using this dataset, we evaluated the sensitivity and specificity of the model. RESULTS: 1214 patients in total were identified. The training set had almost perfect sensitivity and specificity of >0.95; the area under the curve (AUC) was 0.99 (95% CI 0.98-1.00) for creatinine and 0.97 (95% CI: 0.95-0.99) for bilirubin. The validation set had good sensitivity (creatinine: 0.60, 95% CI: 0.55-0.64, bilirubin: 0.54, 95% CI: 0.52-0.56), and specificity (creatinine 0.98, 95% CI: 0.96-0.99, bilirubin 0.90, 95% CI: 0.87-0.94) and area under the curve (creatinine: 0.76, 95% CI: 0.70, 0.82, bilirubin 0.72, 95% CI: 0.68-0.76). CONCLUSIONS: We have demonstrated that a MLP model can be used to reduce the number of blood tests required for some patients at low risk of organ dysfunction, whilst improving safety for others at high risk.