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Background Bivalent messenger RNA (mRNA) vaccines, designed to combat emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, incorporate ancestral strains and a new variant. Our study assessed the immune response in previously vaccinated individuals of the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS) following bivalent mRNA vaccination. Methods Eligible SHCS and STCS participants received approved bivalent mRNA SARS-CoV-2 vaccines (mRNA-1273.214 or BA.1-adapted BNT162b2) within clinical routine. Blood samples were collected at baseline, 4 weeks, 8 weeks, and 6 months postvaccination. We analyzed the proportion of participants with anti-spike protein antibody response ≥1642 units/mL (indicating protection against SARS-CoV-2 infection), and in a subsample T-cell response (including mean concentrations), stratifying results by cohorts and population characteristics. Results In SHCS participants, baseline anti-spike antibody concentrations ≥1642 units/mL were observed in 87% (96/112), reaching nearly 100% at follow-ups. Among STCS participants, 58% (35/60) had baseline antibodies ≥1642 units/mL, increasing to 80% at 6 months. Except for lung transplant recipients, all participants showed a 5-fold increase in geometric mean antibody concentrations at 4 weeks and a reduction by half at 6 months. At baseline, T-cell responses were positive in 96% (26/27) of SHCS participants and 36% (16/45) of STCS participants (moderate increase to 53% at 6 months). Few participants reported SARS-CoV-2 infections, side-effects, or serious adverse events. Conclusions Bivalent mRNA vaccination elicited a robust humoral response in individuals with human immunodeficiency virus (HIV) or solid organ transplants, with delayed responses in lung transplant recipients. Despite a waning effect, antibody levels remained high at 6 months and adverse events were rare. Clinical Trials Registration. NCT04805125. [ABSTRACT FROM AUTHOR]

This study aimed to A) evaluate changes in pain and function following an outpatient interdisciplinary pain management program (IPMP) for children with different chronic pain conditions and B) explore differences in pain and function at baseline and discharge for different diagnoses.A retrospective chart review was performed for 488 children who participated in an outpatient IPMP. Children’s pain and physical, social, and emotional functioning were assessed at initial evaluation, discharge, and one-to-two-month follow-up. Patients were stratified by diagnosis (complex regional pain syndrome [CRPS], headache, musculoskeletal pain, visceral pain, and widespread pain) to evaluate differences in pain and functioning at baseline and discharge.Children’s pain and function improved from initial evaluation to discharge. Those with headache and musculoskeletal pain exhibited better baseline physical and emotional functioning than other diagnostic groups (p = 0.03; p = 0.005; p = 0.002; p = 0.04). Children with CRPS displayed the worst baseline physical functioning (p = 0.003). Those with widespread pain exhibited the worst baseline emotional functioning at both initial evaluation and discharge (p = 0.009; p = 0.007).Children with CRPS, visceral pain, and widespread pain undergoing treatment in an IPMP exhibited the most impaired baseline functioning, while those with musculoskeletal pain and headache were least impaired. All exhibited improvements in pain and function following the IPMP. [ABSTRACT FROM AUTHOR]

The paper demonstrates the analysis of the stress and strain states of an inhomogeneous structure with an axial symmetrical spheroidal inclusion in an infinite solid under a remote uniform tension load derived from the conditions of the theory of elasticity. With respect to the inhomogeneous structure, the deformations produce constraints that require a complete 3-dimensional analysis in the z, r-coordinate system. The solution generates the stress state of the inclusion and at the interface of the matrix. Spheroidal inclusions in an uniform outer tension stress field deform self-similarly to a rather elongated spheroid. With respect to the compatibility condition and depending on the different elastic moduli and Poisson's ratios in the inclusion and matrix, the solution procedure leads to a system of two linear equations with the magnitudes of the two tractions as unknowns. In this way, the solution is shortened to a twofold statically indeterminate system. The analysis performed leads to an exact solution of the general spheroidal problem in a formulation of stress concentration factors considering the different stiffness parameters of inclusion and matrix. [ABSTRACT FROM AUTHOR]

This work deals with the modeling of solid continua undergoing incompatible deformations due to the presence of microscopic defects like dislocations. Our approach relies on a geometrical description of the medium by the strain tensor and the representation of internal efforts using zeroth- and second-order strain gradients in an infinitesimal framework. At the same time, energetic arguments allow to monitor the corresponding moduli. We provide mathematical and numerical results to support these ideas in the framework of isotropic constitutive laws. [ABSTRACT FROM AUTHOR]

Background and Aims Marine macroalgae ('seaweeds') are critical to coastal ecosystem structure and function, but also vulnerable to the many environmental changes associated with anthropogenic climate change (ACC). The local habitat conditions underpinning observed and predicted ACC-driven changes in intertidal macroalgal communities are complex and probably site-specific and operate in addition to more commonly reported regional factors such as sea surface temperatures. Methods We examined how the composition and functional trait expression of macroalgal communities in SW England varied with aspect (i.e. north–south orientation) at four sites with opposing Equator- (EF) and Pole-facing (PF) surfaces. Previous work at these sites had established that average annual (low tide) temperatures vary by 1.6 °C and that EF-surfaces experience six-fold more frequent extremes (i.e. >30 °C). Key Results PF macroalgal communities were consistently more taxon rich; 11 taxa were unique to PF habitats, with only one restricted to EF. Likewise, functional richness and dispersion were greater on PF-surfaces (dominated by algae with traits linked to rapid resource capture and utilization, but low desiccation tolerance), although differences in both taxon and functional richness were probably driven by the fact that less diverse EF-surfaces were dominated by desiccation-tolerant fucoids. Conclusions Although we cannot disentangle the influence of temperature variation on algal ecophysiology from the indirect effects of aspect on species interactions (niche pre-emption, competition, grazing, etc.), our study system provides an excellent model for understanding how environmental variation at local scales affects community composition and functioning. By virtue of enhanced taxonomic diversity, PF-aspects supported higher functional diversity and, consequently, greater effective functional redundancy. These differences may imbue PF-aspects with resilience against environmental perturbation, but if predicted increases in global temperatures are realized, some PF-sites may shift to a depauperate, desiccation-tolerant seaweed community with a concomitant loss of functional diversity and redundancy. [ABSTRACT FROM AUTHOR]

Background: Deformable image registration (DIR)‐based dose accumulation (DDA) is regularly used in adaptive radiotherapy research. However, the applicability and reliability of DDA for direct clinical usage are still being debated. One primary concern is the validity of DDA, particularly for scenarios with substantial anatomical changes, for which energy‐conservation problems were observed in conceptual studies. Purpose: We present and validate an energy‐conservation (EC)‐based DDA validation workflow and further investigate its usefulness for actual patient data, specifically for lung cancer cases. Methods: For five non‐small cell lung cancer (NSCLC) patients, DDA based on five selective DIR methods were calculated for five different treatment plans, which include one intensity‐modulated photon therapy (IMRT), two intensity‐modulated proton therapy (IMPT), and two combined proton‐photon therapy (CPPT) plans. All plans were optimized on the planning CT (planCT) acquired in deep inspiration breath‐hold (DIBH) and were re‐optimized on the repeated DIBH CTs of three later fractions. The resulting fractional doses were warped back to the planCT using each DIR. An EC‐based validation of the accumulation process was implemented and applied to all DDA results. Correlations between relative organ mass/volume variations and the extent of EC violation were then studied using Bayesian linear regression (BLR). Results: For most OARs, EC violation within 10% is observed. However, for the PTVs and GTVs with substantial regression, severe overestimation of the fractional energy was found regardless of treatment type and applied DIR method. BLR results show that EC violation is linearly correlated to the relative mass variation (R^2 > 0.95) and volume variation (R^2 > 0.60). Conclusion: DDA results should be used with caution in regions with high mass/volume variation for intensity‐based DIRs. EC‐based validation is a useful approach to provide patient‐specific quality assurance of the validity of DDA in radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Eight commercially available percutaneous transluminal coronary angioplasty (PTCA), including semi-compliant and non-compliant balloons, have been assessed in detail on their tip, balloon, shaft, RX-Port, and hypotube design. Important performance characteristics such as tip deformation, balloon elongation, and deflation rate have been quantified. Methods: Five catheters of each model were evaluated during various tests. The robustness of the tips was evaluated through compression, measuring any occurrence of damage. The longitudinal growth of the balloons was recorded during inflation up to Rated Burst Pressure (RBP). The forces required to move the catheter forward and retract it into the guide catheter were measured in a simulated use test setup. The deflation behavior was studied by measuring extracted contrast media over time. Furthermore, balloon compliance and catheter dimensions were investigated. Results: The outer dimensions of the catheter were found to be smallest at the hypotube (0.59–0.69 mm) and highest at the balloon, respectively, the crossing profile (0.9–1.2 mm). The tip diameter increased after compression by 1.7–22%. Cross-sections of the folded balloons revealed a tri- and two-fold, respectively. The measured balloon elongation ranged from 0.6 to 2.0 mm. After the inflation of the balloon, an increase in friction between the guide wire and the catheter was observed on four catheters. A maximum increase of 0.12 N to 1.07 N was found. Cross-sections of the RX-Port revealed a semicircular-shaped inflation lumen and a circular guide wire lumen. The measured deflation rate ranged from 0.004 to 0.013 µL/s, resulting in an estimated balloon deflation time of 10.2–28.1 s. Conclusion: This study provides valuable insights into the design characteristics of RX PTCA balloon catheters, which can contribute to facilitating the development of improved catheter designs and enhancing clinical outcomes. Distinctions between SC and NC catheters, such as balloon performance and dimensions, are evident. It is important to note that no single catheter excels in all aspects, as each possesses unique strengths. Therefore, it is essential to consider individual intervention requirements when selecting a catheter. The research also identifies specific catheter weaknesses, such as reduced wall thickness, fringes at the tip, and reduced performance characteristics. [ABSTRACT FROM AUTHOR]

Epigenetic variation in plant populations is an important factor in determining phenotype and adaptation to the environment. However, while advances have been made in the molecular and computational methods to analyze the methylation status of a given sample of DNA, tools to profile and compare the methylomes of multiple individual plants or groups of plants at high resolution and low cost are lacking. Here, we describe a computational approach and R package (sounDMR) that leverages the benefits of long read nanopore sequencing to enable robust identification of differential methylation from complex experimental designs, as well as assess the variability within treatment groups and identify individual plants of interest. We demonstrate the utility of this approach by profiling a population of Arabidopsis thaliana exposed to a demethylating agent and identify genomic regions of high epigenetic variability between individuals. Given the low cost of nanopore sequencing devices and the ease of sample preparation, these results show that high resolution epigenetic profiling of plant populations can be made more broadly accessible in plant breeding and biotechnology. [ABSTRACT FROM AUTHOR]

The article explores three themes in the study of science and medicine for a broader understanding of the entanglement of science and society in South Asia and the production of scientific knowledge in local languages. Topics include the interface between European and indigenous knowledge; the role of language in scientific and medical knowledge production; and the continuity and transformation of knowledge traditions under British rule.

Background Pneumocystis jirovecii pneumonia (PCP) is a serious, emerging complication of coronavirus disease 2019 (COVID-19). Methods We performed a systematic review of published cases. We describe 6 new cases of PCP/COVID-19 coinfection. Among our cases (n = 6) and those in the literature (n = 69) with available data, the median age (interquartile range [IQR]) was 59 (44–77) years (n = 38), 72% (47/65) were male, and the mortality rate was 30.9% (21/68). Results Long-term corticosteroid use was noted in 45.1% (23/51), advanced HIV infection (defined as a CD4 count <200 cells/μL) in 17.6% (9/51), and antineoplastic chemotherapy in 13.7% (7/51), consistent with known PCP risk factors. Notably, 56.7% (38/47) had verifiable risk factors for PCP (high-dose corticosteroids, immunosuppressive therapy, and HIV infection) before COVID-19 infection. A median absolute lymphocyte count (IQR) of 0.61 (0.28–0.92) ×103 cells/mm3 (n = 23) and CD4 count (IQR) of 66 (33–291.5) cells/mm3 (n = 20) were also discovered among the study population. Conclusions These findings suggest a need for greater attention to PCP risk factors among COVID-19 patients and consideration of PCP prophylaxis in these high-risk populations. [ABSTRACT FROM AUTHOR]

Finite-element (FE) simulations that go beyond the linear elastic limit of materials can aid the development of polymeric products such as stretch blow molded angioplasty balloons. The FE model requires the input of an appropriate elastoplastic material model. Up to the onset of necking, the identification of the hardening curve is well established. Subsequently, additional information such as the cross-section and the triaxial stress state inside the specimen is required. The present study aims to inversely identify the post-necking hardening behavior of the semi-crystalline polymer polyamide 12 (PA12) at different temperatures. Our approach uses structural FE simulations of a dog-bone tensile specimen in LS-DYNA with mesh sizes of 1 mm and 2 mm, respectively. The FE simulations are coupled with an optimization routine defined in LS-OPT to identify material properties matching the experimental behavior. A Von Mises yield criterion coupled with a user-defined hardening curve (HC) were considered. Up to the beginning of necking, the Hockett–Sherby hardening law achieved the best fit to the experimental HC. To fit the entire HC until fracture, an extension of the Hockett–Sherby law with power-law functions achieved an excellent fit. Comparing the simulation and the experiment, the following coefficient of determination R 2 could be achieved: Group I: R 2 > 0.9743; Group II: R 2 > 0.9653; Group III: R 2 > 0.9927. Using an inverse approach, we were able to determine the deformation behavior of PA12 under uniaxial tension for different temperatures and mathematically describe the HC. [ABSTRACT FROM AUTHOR]

Purpose: Advanced non‐small cell lung cancer (NSCLC) is still a challenging indication for conventional photon radiotherapy. Proton therapy has the potential to improve outcomes, but proton treatment slots remain a limited resource despite an increasing number of proton therapy facilities. This work investigates the potential benefits of optimally combined proton–photon therapy delivered using a fixed horizontal proton beam line in combination with a photon Linac, which could increase accessibility to proton therapy for such a patient cohort. Materials and methods: A treatment planning study has been conducted on a patient cohort of seven advanced NSCLC patients. Each patient had a planning computed tomography scan (CT) and multiple repeated CTs from three different days and for different breath‐holds on each day. Treatment plans for combined proton–photon therapy (CPPT) were calculated for individual patients by optimizing the combined cumulative dose on the initial planning CT only (non‐adapted) as well as on each daily CT respectively (adapted). The impact of inter‐fractional changes and/or breath‐hold variability was then assessed on the repeat breath‐hold CTs. Results were compared to plans for IMRT or IMPT alone, as well as against combined treatments assuming a proton gantry. Plan quality was assessed in terms of dosimetric, robustness and NTCP metrics. Results: Combined treatment plans improved plan quality compared to IMRT treatments, especially in regard to reductions of low and medium doses to organs at risk (OARs), which translated into lower NTCP estimates for three side effects. For most patients, combined treatments achieved results close to IMPT‐only plans. Inter‐fractional changes impact mainly the target coverage of combined and IMPT treatments, while OARs doses were less affected by these changes. With plan adaptation however, target coverage of combined treatments remained high even when taking variability between breath‐holds into account. Conclusions: Optimally combined proton‐photon plans improve treatment plan quality compared to IMRT only, potentially reducing the risk of toxicity while also allowing to potentially increase accessibility to proton therapy for NSCLC patients. [ABSTRACT FROM AUTHOR]

Recently, PFASs toxicity for the human immune system has become a growing concern. However, there is currently limited information on PFASs immunotoxicity beyond PFHxS, PFOA, PFOS, and PFNA. Therefore, it is urgent to close the present knowledge gap by testing a wider range of compounds. In the present study, twelve compounds were tested for a relationship between the chain-length and headgroup of a PFAS and its cytotoxic for THP-1. As such, THP-1, either as monocytes or differentiated macrophages, were exposed to PFASs in a concentration range of 0–800 μM for either 3 or 24 h. After that, cell viability and reactive oxygen species (ROS) generation were assessed using MTT and DCFH assay, respectively. PFASs' cytotoxicity is dependent on both their chain-length and headgroups. Cell viability decreased with increasing chain-length, and FTOHs displayed markedly higher toxicity than PFCAs and PFSAs. PFASs were ranked based on their calculated Relative Potency Factor. The ranking for the cytotoxicity data on monocytes appears to be 6:2 FTOH ≫ PFNA > PFDA > PFOS > PFOA >4: 2 FTOH > PFHxS = PFHxA > PFBA. For macrophages, this ranking was as follows: 6:2 FTOH >4:2 FTOH > PFOS > PFDA > PFNA > PFOA > PFHxS. The results observed for the ROS generating potential differed as FTOHs generated no ROS. Here, the ranking in monocytes was PFOA > PFNA > PFOS > PFHxS > PFDA > PFHxA = PFBS = PFBA. The ranking for macrophages was PFNA > PFDA ≥ PFOA > PFOS > PFHxA > PFHxS > PFBA = PFBS. In conclusion, the carbon chain-length and functional headgroup of a PFAS are major determinants for their toxicity to THP-1 cells. Furthermore, our study demonstrates the most potent cytotoxic effect for FTOHs in vitro, which has not been observed before to the authors' knowledge. [Display omitted] • The cytotoxicity of perfluoroalkyl compounds for monocytes THP-1 and THP-1 derived macrophages is chain-length and headgroup-dependent. • Perfluoroalkyl compounds with alcoholic headgroups (FTOH) are markedly more cytotoxic than their sulfonic or carboxylic counterparts. • The reactive oxygen species generation after perfluoroalkyl compounds exposure for monocytes THP-1 and THP-1 derived macrophages is chain-length and headgroup-dependent. • Exposure to perfluoroalkyl compounds with alcoholic headgroups (FTOH) generated no significant reactive oxygen species. [ABSTRACT FROM AUTHOR]

The use of cannabinoids in veterinary medicine has been increasing exponentially recently and there is little information regarding the pharmacokinetics of cannabinoids except for cannabidiol (CBD) and tetrahydrocannabinol (THC), with even more sparse information related to their native acid forms found in cannabis. Cannabigerol (CBG) is the precursor molecule to cannabinoid formation in the cannabis plant which may have medicinal properties as well, yet there are no publications related to CBG or the native cannabigerolic acid (CBGA) in companion animal species. The aim of this study was to investigate similar dosing of CBG and CBGA from hemp plants that have been used for cannabidiol pharmacokinetic studies. Administration in the fed and fasted state was performed to better understand absorption and retention of these unique hemp‐derived cannabinoids in dogs. Results suggest that when providing a hemp‐derived CBG/CBGA formulation in equal quantities, CBGA is absorbed approximately 40‐fold better than CBG regardless of being given to fed or fasted dogs. After twice daily dosing for two weeks at 2 mg/kg in the fasted and then fed state, no differences in the mean serum CBG (5 ng/ml) or CBGA (250 ng/ml) serum concentrations were observed between states. Importantly, physical examination, complete blood counts, and serum chemistry evaluations over the two weeks suggest no adverse events during this short‐term dosing trial. [ABSTRACT FROM AUTHOR]

Background: Metal-on-metal hip resurfacing arthroplasty (MMHRA) is typically used in young and active patients because they have the most to gain from this bone-preserving procedure. However, there is very little long-term data on the performance of MMHRA in patients 65 years of age or older because of the efficacy of conventional total hip arthroplasty in this patient population. Methods: 109 patients (124 hips) age ⩾65 years were treated with Conserve Plus MMHRA. There were 83 male and 26 female patients. Their mean age at surgery was 69.5 (range 65–83) years. UCLA hip scores, SF-12 quality of life score were collected at follow-up visits. Radiographic and survivorship analyses were performed. Results: SF-12 scores and UCLA scores were maintained over time except for a small decrease in activity. 4 patients underwent revision surgery. The 15-year Kaplan-Meier survivorship of the cohort was 93.7%. All revisions surgeries were successful at a mean follow-up time of 113 (range 30–218) months. Unusual radiographic findings from our previous publication did not progress over time except for 1 hip that showed a complete radiolucency around the acetabular component. Conclusions: Our results clearly show that HRA is a viable prosthetic solution with many advantages for all active patients, regardless of their age at the time of surgery. [ABSTRACT FROM AUTHOR]

Purpose: This paper provides a self-contained introduction to the mathematical aspects of the topological derivative. Design/methodology/approach: Full justifications are given on simple model problems following a modern approach based on the averaged adjoint state technique. Extensions are discussed in relation with the literature on the field. Findings: Closed expressions of topological derivatives are obtained and commented. Originality/value: Several cases are covered in a unified and didactic presentation. Some elements of proof are novel. [ABSTRACT FROM AUTHOR]

This article revolves around the total perimeter functional, one particular version of the perimeter of a shape Ω contained in a fixed computational domain D measuring the total area of its boundary ∂Ω, as opposed to its relative perimeter, which only takes into account the regions of ∂Ω strictly inside D. We construct and analyze approximate versions of the total perimeter which make sense for general "density functions" u, as generalized characteristic functions of shapes. Their use in the context of density-based topology optimization is particularly convenient insofar as they do not involve the gradient of the optimized function u. Two different constructions are proposed: while the first one involves the convolution of the function u with a smooth mollifier, the second one is based on the resolution of an elliptic boundary-value problem featuring Robin boundary conditions. The "consistency" of these approximations with the original notion of total perimeter is appraised from various points of view. At first, we prove the pointwise convergence of our approximate functionals, then the convergence of their derivatives, as the level of smoothing tends to 0, when the considered density function u is the characteristic function of a "regular enough" shape Ω ⊂ D. Then, we focus on the Γ-convergence of the second type of approximate total perimeter functional, that based on elliptic regularization. Several numerical examples are eventually presented in two and three space dimensions to validate our theoretical findings and demonstrate the efficiency of the proposed functionals in the context of structural optimization. [ABSTRACT FROM AUTHOR]

Bacterial nanocompartments, also known as encapsulins, are an emerging class of protein-based 'organelles' found in bacteria and archaea. Encapsulins are virus-like icosahedral particles comprising a ~ 25–50 nm shell surrounding a specific cargo enzyme. Compartmentalization is thought to create a unique chemical environment to facilitate catalysis and isolate toxic intermediates. Many questions regarding nanocompartment structure–function remain unanswered, including how shell symmetry dictates cargo loading and to what extent the shell facilitates enzymatic activity. Here, we explore these questions using the model Thermotoga maritima nanocompartment known to encapsulate a redox-active ferritin-like protein. Biochemical analysis revealed the encapsulin shell to possess a flavin binding site located at the interface between capsomere subunits, suggesting the shell may play a direct and active role in the function of the encapsulated cargo. Furthermore, we used cryo-EM to show that cargo proteins use a form of symmetry-matching to facilitate encapsulation and define stoichiometry. In the case of the Thermotoga maritima encapsulin, the decameric cargo protein with fivefold symmetry preferentially binds to the pentameric-axis of the icosahedral shell. Taken together, these observations suggest the shell is not simply a passive barrier—it also plays a significant role in the structure and function of the cargo enzyme. [ABSTRACT FROM AUTHOR]

Background: Percutaneous transluminal coronary angioplasty (PTCA) balloon catheters must withstand high pressures required for the lesion treatment, pushing loads during insertion, and pulling loads during withdrawal. These loads pose a challenge especially for polymeric tubular shafts with small cross sections. In order to enable new design innovations and to better understand the mechanics of current catheter technologies, the tensile properties of polyamide (PA) 12 were investigated. PA 12 dog bone specimens and medical PA 12 tubes were either stored at ambient temperature and humidity or conditioned in water, and subjected to tensile loads at different temperatures. In addition, the effect on the tensile properties of the necking process, a forming process to reduce the wall thickness of the tubes, was determined.Results: The tested tubes showed a reduction in both Young's Modulus (- 41.5%) and yield stress (- 29.2%) compared to standardized specimens. Furthermore, an increase in temperature and water absorption softens the material and reduces the mechanical properties like the Young's Modulus and the yield stress. It was found that the material strengthens during the necking process. Likely due to the orientation of the polymers chain molecules in load direction (Rösler et al., 2007), the Young's Modulus of the material could be increased by 43.5%. Furthermore, the absence of a yield point after necking allows for a greater loading capacity of the material without unstable neck growth. Besides the strengthening, the ultimate strain is reduced by 50%. This indicates that the necking process induces plastic deformation.Conclusion: The investigation showed that the environmental conditions like temperature and humidity can influence mechanical properties. It could also be shown that pre-forming processes such as necking can enhance the mechanical properties, such as the Young's Modulus, while reducing the wall thickness. These findings suggest possible further development of catheters with a small cross section and higher mechanical strength and highlight the importance to account for the targeted operating temperature during the design process. [ABSTRACT FROM AUTHOR]

Background: Community-based antiretroviral therapy (ART) dispensing by lay workers is an important differentiated service delivery model in sub-Sahara Africa. However, patients new in care are generally excluded from such models. Home-based same-day ART initiation is becoming widespread practice, but linkage to the clinic is challenging. The pragmatic VIBRA (Village-Based Refill of ART) trial compared ART refill by existing lay village health workers (VHWs) versus clinic-based refill after home-based same-day ART initiation.Methods and Findings: The VIBRA trial is a cluster-randomized open-label clinical superiority trial conducted in 249 rural villages in the catchment areas of 20 health facilities in 2 districts (Butha-Buthe and Mokhotlong) in Lesotho. In villages (clusters) randomized to the intervention arm, individuals found to be HIV-positive during a door-to-door HIV testing campaign were offered same-day ART initiation with the option of refill by VHWs. The trained VHWs dispensed drugs and scheduled clinic visits for viral load measurement at 6 and 12 months. In villages randomized to the control arm, participants were offered same-day ART initiation with clinic-based ART refill. The primary outcome was 12-month viral suppression. Secondary endpoints included linkage and 12-month engagement in care. Analyses were intention-to-treat. The trial was registered on ClinicalTrials.gov (NCT03630549). From 16 August 2018 until 28 May 2019, 118 individuals from 108 households in 57 clusters in the intervention arm, and 139 individuals from 130 households in 60 clusters in the control arm, were enrolled (150 [58%] female; median age 36 years [interquartile range 30-48]; 200 [78%] newly diagnosed). In the intervention arm, 48/118 (41%) opted for VHW refill. At 12 months, 46/118 (39%) participants in the intervention arm and 64/139 (46%) in the control arm achieved viral suppression (adjusted risk difference -0.07 [95% CI -0.20 to 0.06]; p = 0.256). Arms were similar in linkage (adjusted risk difference 0.03 [-0.10 to 0.16]; p = 0.630), but engagement in care was non-significantly lower in the intervention arm (adjusted risk difference -0.12 [-0.23 to 0.003]; p = 0.058). Seven and 0 deaths occurred in the intervention and control arm, respectively. Of the intervention participants who did not opt for drug refill from the VHW at enrollment, 41/70 (59%) mentioned trust or conflict issues as the primary reason. Study limitations include a rather small sample size, 9% missing viral load measurements in the primary endpoint window, the low uptake of the VHW refill option in the intervention arm, and substantial migration among the study population.Conclusions: The offer of village-based ART refill after same-day initiation led to similar outcomes as clinic-based refill. The intervention did not amplify the effect of home-based same-day ART initiation alone. The findings raise concerns about acceptance and safety of ART delivered by lay health workers after initiation in the community.Trial Registration: Registered with Clinicaltrials.gov (NCT03630549). [ABSTRACT FROM AUTHOR]

Background: Radiomics is a promising tool for identifying imaging-based biomarkers. Radiomics-based models are often trained on single-institution datasets; however, multi-centre imaging datasets are preferred for external generalizability owing to the influence of inter-institutional scanning differences and acquisition settings. The study aim was to determine the value of preselection of robust radiomic features in routine clinical positron emission tomography (PET) images to predict clinical outcomes in locally advanced non-small cell lung cancer (NSCLC). Methods: A total of 1404 primary tumour radiomic features were extracted from pre-treatment [18F]fluorodeoxyglucose (FDG)-PET scans of stage IIIA/N2 or IIIB NSCLC patients using a training cohort (n = 79; prospective Swiss multi-centre randomized phase III trial SAKK 16/00; 16 centres) and an internal validation cohort (n = 31; single centre). Robustness studies investigating delineation variation, attenuation correction and motion were performed (intraclass correlation coefficient threshold > 0.9). Two 12-/24-month event-free survival (EFS) and overall survival (OS) logistic regression models were trained using standardized imaging: (1) with robust features alone and (2) with all available features. Models were then validated using fivefold cross-validation, and validation on a separate single-centre dataset. Model performance was assessed using area under the receiver operating characteristic curve (AUC). Results: Robustness studies identified 179 stable features (13%), with 25% stable features for 3D versus 4D acquisition, 31% for attenuation correction and 78% for delineation. Univariable analysis found no significant robust features predicting 12-/24-month EFS and 12-month OS (p value > 0.076). Prognostic models without robust preselection performed well for 12-month EFS in training (AUC = 0.73) and validation (AUC = 0.74). Patient stratification into two risk groups based on 12-month EFS was significant for training (p value = 0.02) and validation cohorts (p value = 0.03). Conclusions: A PET-based radiomics model using a standardized, multi-centre dataset to predict EFS in locally advanced NSCLC was successfully established and validated with good performance. Prediction models with robust feature preselection were unsuccessful, indicating the need for a standardized imaging protocol. [ABSTRACT FROM AUTHOR]

Anthropogenic climate change is widely predicted to influence essential ecosystem services such as decomposition and nutrient cycling, but consistent patterns of response to observed or predicted shifts in climate have proven difficult to evidence. We investigated how aspect (i.e., Pole- (PF) and Equator-facing (EF) roadside grassy verges in SW England), a natural model for variation in soil temperature, influenced soil physicochemical conditions, earthworm communities, and oak leaf litter decomposition. Average above-ground daily annual temperatures for EF-slopes were 1.96 °C higher than PF-slopes, with even more marked variation in average mean daily maximum and extreme temperatures (i.e., an average of three-fold more days where temperature exceeded 30 °C). Despite these differences, of the soil physicochemical factors quantified, only soil moisture (0–15 cm deep) varied consistently with aspect, being higher on the cooler PF slopes. Similarly, we detected no significant variation in litter decomposition. Despite low abundances there were, however, differences in earthworm assemblages between PF- and EF- slopes, with 7 of 14 species restricted to cooler, moister PF verges. Consequently, we conclude that despite consistent aspect-linked differences in the local microclimate, soil-based patterns and processes in semi-natural, temperate grassland ecosystems are relatively well buffered from the magnitude of temperature variation within the range predicted by the IPCC SSP1-2.6 emissions scenario. Nonetheless, the restricted distribution of half the earthworm species, and two functional groups to PF-slopes, supports studies suggesting that temperate increases associated with higher emissions scenarios will negatively influence some species, and the vital soil bioturbation processes that they provide. [ABSTRACT FROM AUTHOR]

The governing principles and suites of genes for lateral elongation or incorporation of new cell wall material along the length of a rod-shaped cell are well described. In contrast, relatively little is known about unipolar elongation or incorporation of peptidoglycan at one end of the rod. Recent work in three related model systems of unipolar growth (Agrobacterium tumefaciens , Brucella abortus, and Sinorhizobium meliloti) has clearly established that unipolar growth in the Hyphomicrobiales order relies on a set of genes distinct from the canonical elongasome. Polar incorporation of envelope components relies on homologous proteins shared by the Hyphomicrobiales, reviewed here. Ongoing and future work will reveal how unipolar growth is integrated into the alphaproteobacterial cell cycle and coordinated with other processes such as chromosome segregation and cell division. • Unipolar growth relies on a conserved set of genes distinct from the Rod system. • PBP1a is the primary driver of unipolar peptidoglycan biosynthesis. • Growth polarity is established by RgsS, an FtsN-like protein. • Unipolar growth coordinates insertion of peptidoglycan, OMPs, and LPS at the growth pole. [ABSTRACT FROM AUTHOR]

Deformable image registration (DIR) is an important component for dose accumulation and associated clinical outcome evaluation in radiotherapy. However, the resulting deformation vector field (DVF) is subject to unavoidable discrepancies when different algorithms are applied, leading to dosimetric uncertainties of the accumulated dose. We propose here an approach for proton therapy to estimate dosimetric uncertainties as a consequence of modeled or estimated DVF uncertainties. A patient-specific DVF uncertainty model was built on the first treatment fraction, by correlating the magnitude differences of five DIR results at each voxel to the magnitude of any single reference DIR. In the following fractions, only the reference DIR needs to be applied, and DVF geometric uncertainties were estimated by this model. The associated dosimetric uncertainties were then derived by considering the estimated geometric DVF uncertainty, the dose gradient of fractional recalculated dose distribution and the direction factor from the applied reference DIR of this fraction. This estimated dose uncertainty was respectively compared to the reference dose uncertainty when different DIRs were applied individually for each dose warping. This approach was validated on seven NSCLC patients, each with nine repeated CTs. The proposed model-based method is able to achieve dose uncertainty distribution on a conservative voxel-to-voxel comparison within ±5% of the prescribed dose to the 'reference' dosimetric uncertainty, for 77% of the voxels in the body and 66%–98% of voxels in investigated structures. We propose a method to estimate DIR induced uncertainties in dose accumulation for proton therapy of lung tumor treatments. [ABSTRACT FROM AUTHOR]

Objectives: WHO guidelines on ART define the HIV-1 viral load (VL) threshold for treatment failure at 1000 copies/mL. The Switch Either near Suppression Or THOusand (SESOTHO) trial, conducted in Lesotho from 2017 to 2020, found that patients with persistent viraemia below this threshold (100-999 copies/mL) benefit from switching to second-line ART. This pre-planned nested study assesses the prevalence of resistance-associated mutations (RAMs) in SESOTHO trial participants.Methods: The SESOTHO trial [registered at ClinicalTrials.gov (NCT03088241)] enrolled 80 persons taking NNRTI-based first-line ART with low-level HIV-1 viraemia (100-999 copies/mL) and randomized them (1:1) to switch to a PI-based second-line regimen (switch) or continue on first-line therapy (control). We sequenced relevant regions of the viral pol gene using plasma samples obtained at enrolment and 36 weeks. RAMs were classified with the Stanford HIV Drug Resistance Database.Results: Sequencing data were obtained for 37/80 (46%) participants at baseline and 26/48 (54%) participants without viral suppression to <50 copies/mL at 36 weeks (21 control participants and 5 switch participants). At baseline, 31/37 (84%) participants harboured high-level resistance to at least two drugs of their current regimen. At 36 weeks, 17/21 (81%) control participants harboured resistance to at least two drugs of their current regimen, while no PI-associated resistance was detected in the 5 switch participants with ongoing viraemia.Conclusions: Among persons with low-level viraemia while taking NNRTI-based first-line ART enrolled in the SESOTHO trial, the majority harboured HIV-1 with RAMs that necessitate ART modification. These findings support lowering the VL threshold triggering a switch to second-line ART in future WHO guidelines. [ABSTRACT FROM AUTHOR]

In the present work, solutions are recapitulated according to the theory of elasticity for the deformations of an adhesive spherical inhomogeneity in an infinite matrix under remote uniform axial and axial-symmetrical radial tension. Stress fields in the inhomogeneity and at the interface in the matrix are provided, too. It is shown that the sphere is deformed to a spheroid under any of the loading cases considered. Due to the axial-symmetric setup of the problem, the deformation is fully described by the two displacement values at line segments on the principal axes of the spheroid. The displacements depend on the applied remote load and on two traction fields at the inhomogeneity-matrix interface. For any combination of inhomogeneity and matrix stiffness, the condition of compatibility of deformations yields a system of two linear equations with the two magnitudes of the tractions as unknowns. Thus, the problem is reduced to a formulation for solving a twofold statically indetermined structure. The system is solved and the exact solution of the general spherical inhomogeneity problem with differing stiffness in terms of Young's moduli and Poisson's ratios of inclusion and matrix is presented. [ABSTRACT FROM AUTHOR]

Background: Impulse control disorders (ICDs) are a frequent side effect of dopamine replacement therapy (DRT) in Parkinson's disease (PD). Reckless generosity might expand the spectrum of known ICDs. Cases: Over 18 months, we encountered three PD patients exhibiting reckless generosity under DRT, leading to disastrous financial and social consequences. Literature Review: Except for another case series describing reckless generosity in three PD patients, only one study has examined generosity in PD patients; with findings suggesting that PD patients with ICDs are less sensitive to the aversive aspects of the lack of reciprocation in social settings. Studies with healthy individuals suggest that increased availability of dopamine might reduce social discounting and promote egalitarian behavior, and thereby increase generous behavior towards strangers. Genetic studies show that polymorphisms in dopamine D4 receptors influence generous behavior. Conclusions: Reckless generosity in PD patients with DRT might be underreported and should therefore be carefully be screened for by clinicians. A potential mechanism underlying this ICD‐related behavior might be a sensitization of the mesolimbic and mesocortical dopaminergic system, leading to reduced social discounting and maladaptive reward‐learning. Further research is needed to investigate the prevalence and underlying mechanisms of reckless generosity in PD patients. [ABSTRACT FROM AUTHOR]

Minimal partition problems consist in finding a partition of a domain into a given number of components in order to minimize a geometric criterion. In applicative fields such as image processing or continuum mechanics, it is standard to incorporate in this objective an interface energy that accounts for the lengths of the interfaces between components. The present work is focused on the theoretical and numerical treatment of minimal partition problems with such interface energies. The considered approach is based on a Γ-convergence approximation combined with convex analysis techniques. [ABSTRACT FROM AUTHOR]

Organizational gender equality policies must address critical issues in organizations, as well as challenge hierarchies and the unequal distribution of power and resources. At the same time, they are reliant on acceptance by organizations when developing an official course of action. On the basis of a neo‐institutional perspective, this study investigates how gender equality discourses are disciplined so that they fit organizational expectations by maintaining the rationality myth of the organization. The empirical analysis of four Swiss organizations demonstrates that, although they intend to reduce gender inequalities, their gender equality policies are shaped by a logic of appropriateness that leads to a continuous reproduction of heteronormativity within gender equality policies. This study thus contributes to the understanding of how the logic of appropriateness protects the heteronormative matrix in organizations by disciplining gender equality discourses. [ABSTRACT FROM AUTHOR]

Refugees face various nutritional challenges during and after migration. This cross-sectional, mixed-methods study seeks to investigate the prevalence of undernutrition and obesity among refugees in Geneva, and to identify barriers to healthy eating. Anthropometric measurements of 354 adult refugees were collected between 2017 and 2019 by trained nurses and dietitians. Seven focus group discussions totaling 51 participants, refugees and social workers, investigated conceptions and needs regarding diet. The mean Body Mass Index is 24.6 ± 4.8 kg/m2. Women are disproportionately affected by obesity compared to men (p < 0.001). Weight gain post-migration is correlated positively with length of stay in Geneva (p < 0.001). Major obstacles to healthy eating are economic and linguistic. For participants, cooking workshops and free physical activities are highly needed interventions. Post-migration lifestyle interventions should be implemented to prevent weight gain in this population. Such interventions must be multi-level, to overcome structural, social and behavioral barriers to healthy eating. [ABSTRACT FROM AUTHOR]

Background The CASCADE trial showed that compared with usual care (UC), offering same-day (SD) antiretroviral therapy (ART) during home-based human immunodeficiency virus testing improved engagement in care and viral suppression 12 months after diagnosis. However, questions remain regarding long-term outcomes and the risk of propagating drug resistance. Methods After completion of the primary endpoint at 12 months, participants not in care in both arms were traced and encouraged to access care. At 24 months, the following outcomes were assessed in both arms: engagement in care, viral suppression, and reasons for nonengagement. Furthermore, we explored the acquisition of drug resistance mutations (DRMs) among SD arm nonlinkers. Results At 24 months, 64% (88/137) in the SD arm vs 59% (81/137) in the UC arm were in care (absolute difference [AD], 5%; 95% confidence interval [CI], −6 to16; P =.38) and 57% (78/137) vs 54% (74/137) had documented viral suppression (AD, 3%; 95% CI, −9 to 15; P =.28). Among 36 participants alive and not in care at 24 months with ascertained status, the majority rejected contact with the health system or were unwilling to take ART. Among 8 interviewed SD arm nonlinkers, 6 had not initiated ART upon enrollment, and no acquired DRMs were detected. Two had taken the initial 30-day ART supply and acquired DRMs. Conclusions SD ART resulted in higher rates of engagement in care and viral suppression at 12 months but not at 24 months. Leveling off between both arms was driven by linkage beyond 12 months in the UC arm. We did not observe compensatory long-term disengagement in the SD arm. These long-term results endorse SD ART initiation policies. Clinical Trials Registration NCT02692027. [ABSTRACT FROM AUTHOR]

Background: Current World Health Organization (WHO) antiretroviral therapy (ART) guidelines define virologic failure as two consecutive viral load (VL) measurements ≥1,000 copies/mL, triggering empiric switch to next-line ART. This trial assessed if patients with sustained low-level HIV-1 viremia on first-line ART benefit from a switch to second-line treatment.Methods and Findings: This multicenter, parallel-group, open-label, superiority, randomized controlled trial enrolled patients on first-line ART containing non-nucleoside reverse transcriptase inhibitors (NNRTI) with two consecutive VLs ≥100 copies/mL, with the second VL between 100-999 copies/mL, from eight clinics in Lesotho. Consenting participants were randomly assigned (1:1), stratified by facility, demographic group, and baseline VL, to either switch to second-line ART (switch group) or continued first-line ART (control group; WHO guidelines). The primary endpoint was viral suppression (<50 copies/mL) at 36 weeks. Analyses were by intention to treat, using logistic regression models, adjusted for demographic group and baseline VL. Between August 1, 2017, and August 7, 2019, 137 individuals were screened, of whom 80 were eligible and randomly assigned to switch (n = 40) or control group (n = 40). The majority of participants were female (54 [68%]) with a median age of 42 y (interquartile range [IQR] 35-51), taking tenofovir disoproxil fumarate/lamivudine/efavirenz (49 [61%]) and on ART for a median of 5.9 y (IQR 3.3-8.6). At 36 weeks, 22/40 (55%) participants in the switch versus 10/40 (25%) in the control group achieved viral suppression (adjusted difference 29%, 95% CI 8%-50%, p = 0.009). The switch group had significantly higher probability of viral suppression across different VL thresholds (<20, <100, <200, <400, and <600 copies/mL) but not for <1,000 copies/mL. Thirty-four (85%) participants in switch group and 21 (53%) in control group experienced at least one adverse event (AE) (p = 0.002). No hospitalization or death or other serious adverse events were observed. Study limitations include a follow-up period too short to observe differences in clinical outcomes, missing values in CD4 cell counts due to national stockout of reagents during the study, and limited generalizability of findings to other than NNRTI-based first-line ART regimens.Conclusions: In this study, switching to second-line ART among patients with sustained low-level HIV-1 viremia resulted in a higher proportion of participants with viral suppression. These results endorse lowering the threshold for virologic failure in future WHO guidelines.Trial Registration: The trial is registered at ClinicalTrials.gov, NCT03088241. [ABSTRACT FROM AUTHOR]

Introduction: Home‐based HIV testing fails to reach high coverage among adolescents and young adults (AYA), mainly because they are often absent during the day of home‐based testing. ADORE (ADolescent ORal tEsting) is a mixed‐method nested study among AYA in rural Lesotho, measuring the effect of home‐based secondary distribution of oral HIV self‐tests (HIVST) on coverage, as well as exploring how AYA perceive this HIV self‐testing model. Methods: ADORE study was nested in a cluster‐randomized trial. In intervention village‐clusters, oral HIVST were left for household members who were absent or declined testing during a testing campaign. One present household member was trained on HIVST use. Distributed HIVST were followed up by village health workers (VHW). In control clusters no self‐tests were distributed. The quantitative outcome was testing coverage among AYA (age 12 to 24) within 120 days, defined as a confirmed HIV test result or known status, using adjusted random‐effects logistic regression on the intention‐to‐treat population. Qualitatively, we conducted in‐depth interviews among both AYA who used and did not use the distributed HIVST. Results: From July 2018 to December 2018, 49 and 57 villages with 1471 and 1620 consenting households and 1236 and 1445 AYA in the control and intervention arm, respectively, were enrolled. On the day of the home‐visit, a testing coverage of 37% (461/1236) and 41% (596/1445) in the control and the intervention arm, respectively, were achieved. During the 120 days follow‐up period, an additional 23 and 490 AYA in control and intervention clusters, respectively, knew their status. This resulted in a testing coverage of 484/1236 (39%) in the control versus 1086/1445 (75%) in the intervention arm (aOR 8.80 [95% CI 5.81 to 13.32]; p < 0.001). 21 interviews were performed. Personal assistance after the secondary distribution emerged as a key theme and VHWs were generally seen as a trusted cadre. Conclusions: Secondary distribution of HIVST for AYA absent or refusing to test during home‐based testing in Lesotho resulted in an absolute 36% increase in coverage. Distribution should, however, go along with clear instructions on the use of the HIVST and a possibility to easily access more personal support. [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented which discusses topics within the issue including eighteenth-century library of Tipu Sultan; practice of analysing the contents of Sanskrit manuscripts; and fate of the library of the Anjuman-e Taraqqi-e Urdu after Partition.

This article argues that the history of a damaged Urdu library in Delhi reveals new perspectives on the ways in which prominent Indian Muslim scholars dealt with the violent displacements of the 1947 Partition of British India and imagined new futures for the Urdu language across the borders of India and Pakistan. The library of the Anjuman-e Taraqqi-e Urdu (Association for the Advancement of Urdu), an influential Urdu literary association, was damaged during the violence following Partition in August 1947. In contrast to the relative absence of official commemorations of Partition in post-colonial South Asia, the Anjuman's leaders documented and publicised the violence of Partition on their library. Moreover, these Urdu scholars used the material process of restoring the damaged library in 1947 and 1948 to rethink the role of the library as a repository to preserve evidence of the continuing production of Urdu knowledge in India. In turn, the disputed division of the library in 1949 illuminates competing visions for Urdu's future in India, Pakistan, and beyond. This story of one Urdu library demonstrates how changing library collecting priorities and material practices shaped broader debates over Urdu's place in twentieth-century South Asia. [ABSTRACT FROM AUTHOR]

Background: The need for revision surgery after hip resurfacing arthroplasty (HRA) is more prevalent for women than for men. However, there is a paucity of information to explain this observation. We aimed (1) to determine sex-specific risk factors leading to revision surgery; and (2) to correlate these risk factors to the dominant modes of failure of HRA. Methods: 1101 patients (1375 consecutive hips) including 292 women (355 hips) and 809 men (1020 hips) with a mean age of 51.3 years were included regardless of bone quality. The contact patch to rim distance was computed. Results: A contact patch to rim (CPR) distance of ⩽7 mm, an aetiology of developmental dysplasia, a postoperative abduction-adduction arc of ⩾95°, and a metaphyseal stem left uncemented were risk factors associated with revision surgery for female patients, while a CPR distance of ⩽10 mm, a component size of ⩽46 mm, an age at surgery of ⩽55 years, and an early femoral preparation technique were risk factors for male patients. Hips with no risk factors from the female group had a survivorship of 98.7% at 15 years, matching or exceeding the results of all male subgroups. However the risk factors in the female group increased the risk of revision much more than in the male group. Conclusions: In the absence of risk factors, the survivorship of HRA in female patients is equal to that of males. Many female patients can safely benefit from HRA by excluding severe dysplasia and optimising surgical technique. [ABSTRACT FROM AUTHOR]

The REPRIEVE trial suggests that primary cardiovascular disease (CVD) prevention could be considered among people with HIV at low CVD risk. We found cisgender women with low/moderate and high CVD risk are less likely to receive statins than cisgender men. Efforts are needed to guarantee equal access to statin-based CVD prevention. [ABSTRACT FROM AUTHOR]

Pre-treatment genotyping of four well-characterized toxicity risk-variants in the dihydropyrimidine dehydrogenase gene (DPYD) has been widely implemented in Europe to prevent serious adverse effects in cancer patients treated with fluoropyrimidines. Current genotyping practices are largely limited to selected commonly studied variants and are unable to determine phasing when more than one variant allele is detected. Recent evidence indicates that common DPYD variants modulate the functional impact of deleterious variants in a phase-dependent manner, where a cis- or a trans-configuration translates into different toxicity risks and dosing recommendations. DPYD is a large gene with 23 exons spanning nearly a mega-base of DNA, making it a challenging candidate for full-gene sequencing in the diagnostic setting. Herein, we present a time- and cost-efficient long-read sequencing approach for capturing the complete coding region of DPYD. We demonstrate that this method can reliably produce phased genotypes, overcoming a major limitation with current methods. This method was validated using 21 subjects, including two cancer patients, each of whom carried multiple DPYD variants. Genotype assignments showed complete concordance with conventional approaches. Furthermore, we demonstrate that the method is robust to technical challenges inherent in long-range sequencing of PCR products, including reference alignment bias and PCR chimerism. [ABSTRACT FROM AUTHOR]

• Combined proton–photon therapy (CPPT) increases treatment plan quality vs. IMRT & IMPT. • Increased proton beam flexibility in CPPT increases treatment plan quality further. • Substantial decrease of photon contributions to CPPT with increasing proton beam flexibility. • Probabilities for Xerostomia and Dysphagia reduce with CPPT compared to IMPT, even in the case of an arc-like proton beam flexibility. • CPPT needs adaption for head and neck cancer treatments. This study investigates whether combined proton–photon therapy (CPPT) improves treatment plan quality compared to single-modality intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) for head and neck cancer (HNC) patients. Different proton beam arrangements for CPPT and IMPT are compared, which could be of specific interest concerning potential future upright-positioned treatments. Furthermore, it is evaluated if CPPT benefits remain under inter-fractional anatomical changes for HNC treatments. Five HNC patients with a planning CT and multiple (4–7) repeated CTs were studied. CPPT with simultaneously optimized photon and proton fluence, single-modality IMPT, and IMRT treatment plans were optimized on the planning CT and then recalculated and reoptimized on each repeated CT. For CPPT and IMPT, plans with different degrees of freedom for the proton beams were optimized. Fixed horizontal proton beam line (FHB), gantry-like, and arc-like plans were compared. The target coverage for CPPT without adaptation is insufficient (average V95%=88.4 %), while adapted plans can recover the initial treatment plan quality for target (average V95%=95.5 %) and organs-at-risk. CPPT with increased proton beam flexibility increases plan quality and reduces normal tissue complication probability of Xerostomia and Dysphagia. On average, Xerostomia NTCP reductions compared to IMRT are −2.7 %/-3.4 %/-5.0 % for CPPT FHB/CPPT Gantry/CPPT Arc. The differences for IMPT FHB/IMPT Gantry/IMPT Arc are + 0.8 %/-0.9 %/-4.3 %. CPPT for HNC needs adaptive treatments. Increasing proton beam flexibility in CPPT, either by using a gantry or an upright-positioned patient, improves treatment plan quality. However, the photon component is substantially reduced, therefore, the balance between improved plan quality and costs must be further determined. [ABSTRACT FROM AUTHOR]

In addition to well-known effects on species ecophysiology, phenology, and distributions, climate change is widely predicted to impact essential ecosystem services such as decomposition and nutrient cycling. While temperature and soil moisture are thought to influence litter decomposition, elucidating consistent soil process responses to observed or predicted shifts in climate have proven difficult to evidence. Here we investigated how aspect (i.e., north-south orientation), a natural model for variation in soil temperature, influenced soil physico-chemical conditions and decomposition of two standardised litter types (Green tea and Rooibos teabags) in Pole-facing (PF) and Equator-facing (EF) roadside verges spanning a 3000 km and 27° latitudinal gradient across Europe. Despite average daily temperatures being 1.5 - 3.0 °C warmer on EF than PF slopes, there were only minor region-specific differences in initial soil physico-chemical conditions and short-term variation in litter decomposition (i.e., litter mass loss was higher in EF-verges for the first month of deployment only) associated with aspect. We conclude that previously observed differences in soil environments and the decomposition process associated with slope orientation, is largely litter or environment specific, although medium-term soil-decomposition in semi-natural grassland ecosystems may also be insensitive to the magnitude of temperature variation within the range predicted by the IPCC SSP1–2.6 emissions scenario. Nonetheless, consistent average and extreme temperature differences between adjacent PF- and EF-aspects along roadside verges provides a model system to explore exactly how resilient the soil environment and the micro-organisms responsible for decomposition, are to temperature variation. • Consistent patterns of soil process and organism response to climate shifts remain elusive. • Habitat aspect and latitude greatly affect habitat microclimate. • Soil environment & litter decomposition responses were inconsistent and site-specific. • Litter decay may be unresponsive to warming in the low range IPCC emission scenario. [ABSTRACT FROM AUTHOR]

Background: Hip resurfacing arthroplasty (HRA) typically uses a hybrid design (cemented femoral component and cementless acetabular shell) but has recently been performed with fully cementless components. There is a paucity of information on the clinical performance of these cementless designs. Methods: The UCLA clinical scores, SF-12 quality of life scores, complication rates, survivorship and radiographic signs of loosening or gross stress shielding of 39 hips (39 male patients) implanted with cementless HRA were compared with those of 40 hips (37 male patients) implanted with hybrid HRA during the same time frame. Results: There were no significant differences in postoperative clinical and quality of life scores, complication rates, or radiographic signs of loosening between the 2 groups. The 5-year Kaplan-Meier survivorship was 97.2% for the cementless group and 100% for the hybrid group. This difference was not significant (p = 0.3694). There were no femoral component failures in any of the 2 groups. Conclusions: At a mean follow-up of 6 years, there is no tangible difference between the performance of cementless HRA compared to hybrid HRA. The absence of learning curve associated with this device and the potential for better preservation of femoral neck bone mineral density suggest that this technology is well suited for young patients with good bone quality seeking to resume an active lifestyle including high-impact activities. [ABSTRACT FROM AUTHOR]

This book round table discusses two recent monographs on political violence and revolutionary terrorism in late colonial India, Kama Maclean's A Revolutionary History of Interwar India: Violence, Image, Voice and Text (2015) and Durba Ghosh's Gentlemanly Terrorists: Political Violence and the Colonial State in India, 1919–1947 (2017). Maclean's A Revolutionary History of Interwar India uncovers how revolutionaries in Punjab and northern India reshaped the goals and tactics of the Indian independence movement, especially the policy of nonviolence. Ghosh's Gentlemanly Terrorists explores the relationship of political violence in Bengal to the development of the modern nation-state in India. Both Ghosh and Maclean rethink the conventional narrative of the Indian freedom struggle and connect local developments in South Asia to global trends in anticolonial resistance and to larger conversations about the relationship between democracy and surveillance. In the five review essays, Daniel Elam, Rishad Choudhury, Mou Banerjee, Rohit De, and Michael Silvestri assess the impact of these two monographs on South Asian history, legal studies, histories of religion, studies of anticolonial movements, and British imperial historiography. In their responses, Maclean and Ghosh assess the challenges of writing histories of revolutionaries in the present in relation to the anticipated futures of the revolutionaries themselves. [ABSTRACT FROM AUTHOR]