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Background: There is a dearth of studies evaluating the utility of reporting prognostication among nursing home (NH) residents with cancer. Objective: To study factors associated with documented less than six-month prognosis, and its relationship with end-of-life (EOL) care quality measures among residents with cancer. Methods: The Surveillance, Epidemiology, and End Results linked with Medicare, and the Minimum Data Set databases was used to identify 20,397 NH residents in the United States with breast, colorectal, lung, pancreatic, or prostate cancer who died between July 2016 and December 2018. Of these, 2205 residents (10.8%) were documented with less than six-month prognosis upon NH admission. Main outcomes were more than one hospitalization, more than one emergency department visit, and any intensive care unit admission within the last 30 days of life as aggressive EOL care markers, as well as admission to hospice, receipt of advance care planning and palliative care, and survival. Specificity and sensitivity of prognosis were assessed using six-month mortality as the outcome. Propensity score matching adjusted for selection biases, and logistic regression examined association. Results: Specificity and sensitivity of documented less than six-month prognosis for mortality were 94.2% and 13.7%, respectively. Residents with documented less than six-month prognosis had greater odds of being admitted to hospice than those without (adjusted odds ratio: 3.27, 95% confidence interval: 2.86?3.62), and lower odds to receive aggressive EOL care. Conclusion: In this cohort study, documented less than six-month prognosis was associated with less aggressive EOL care. Despite its high specificity, however, low sensitivity limits its utility to operationalize care on a larger population of residents with terminal illness.

Summary: Background: Lynch Syndrome (LS) is a cancer predisposition syndrome caused by constitutional pathogenic variants in the mismatch repair (MMR) genes. To date, fragmentation of clinical and genomic data has restricted understanding of national LS ascertainment and outcomes, and precluded evaluation of NICE guidance on testing and management. To address this, via collaboration between researchers, the National Disease Registration Service (NDRS), NHS Genomic Medicine Service Alliances (GMSAs), and NHS Regional Clinical Genetics Services, a comprehensive registry of LS carriers in England has been established. Methods: For comprehensive ascertainment of retrospectively identified MMR pathogenic variant (PV) carriers (diagnosed prior to January 1, 2023), information was retrieved from all clinical genetics services across England, then restructured, amalgamated, and validated via a team of trained experts in NDRS. An online submission portal was established for prospective ascertainment from January 1, 2023. The resulting data, stored in a secure database in NDRS, were used to investigate the demographic and genetic characteristics of the cohort, censored at July 25, 2023. Cancer outcomes were investigated via linkage to the National Cancer Registration Dataset (NCRD). Findings: A total of 11,722 retrospective and 570 prospective data submissions were received, resulting in a comprehensive English National Lynch Syndrome Registry (ENLSR) comprising 9030 unique individuals. The most frequently identified pathogenic MMR genes were MSH2 and MLH1 at 37.2% (n = 3362) and 29.1% (n = 2624), respectively. 35.9% (n = 3239) of the ENLSR cohort received their LS diagnosis before their first cancer diagnosis (presumptive predictive germline test). Of these, 6.3% (n = 204) developed colorectal cancer, at a median age of initial diagnosis of 51 (IQR 40–62), compared to 73 years (IQR 64–80) in the general population (p

Objectives Previous studies have suggested that fibrates and glitazones may have a role in brain tumour prevention. We examined if there is support for these observations using primary care records from the UK Clinical Practice Research Datalink (CPRD).Design We conducted two nested case–control studies using primary and secondary brain tumours identified within CPRD between 2000 and 2016. We selected cases and controls among the population of individuals who had been treated with any anti-diabetic or anti-hyperlipidaemic medication to reduce confounding by indication.Setting Adults older than 18 years registered with a general practitioner in the UK contributing data to CPRD.Results We identified 7496 individuals with any brain tumour (4471 primary; 3025 secondary) in total. After restricting cases and controls to those prescribed any anti-diabetic or anti-hyperlipidaemic medication, there were 1950 cases and 7791 controls in the fibrate and 480 cases with 1920 controls in the glitazone analyses. Longer use of glitazones compared with all other anti-diabetic medications was associated with a reduced risk of primary (adjusted OR (aOR) 0.89 per year, 95% CI 0.80 to 0.98), secondary (aOR 0.87 per year, 95% CI 0.77 to 0.99) or combined brain tumours (aOR 0.88 per year, 95% CI 0.81 to 0.95). There was little evidence that fibrate exposure was associated with risk of either primary or secondary brain tumours.Conclusions Longer exposure to glitazones was associated with reduced primary and secondary brain tumour risk. Further basic science and population-based research should explore this finding in greater detail, in terms of replication and mechanistic studies.

Summary: Termite-built topology is complex due to group interactions and environmental feedback. Being interlinked with material characteristics and related to functionality, an accurate synthesis of termite mound topology has never been achieved. We scanned inner termite mound pieces via high-resolution micro-computed tomography. A wavelet scattering transform followed by optimization extracts features that are fed into a Gaussian Random Fields (GRFs) approach to synthesize termite-mimetic spinodal topology. Compared to natural structures the GRF topology is more regular. Irregularity is related to anisotropy, indicative of directionality caused by porous network connectivity of chambers and corridors. Since GRFs are related to diffusion, we assume that deterministic behavioral traits play a significant role in the development of these local differences. We pioneer a framework to reliably mimic termite mound spinodal features. Engineering termite-inspired structures will allow to inspect aspects of termite architectures and their behavior to manufacture novel material concepts with imprinted multi-functionality.

Abstract This report describes the case of a 70-year-old man with metastatic squamous cell carcinoma (SCC) of the right lower leg. Soon after definitive surgical management of the primary and nodal metastases with curative intent, he relapsed, developing aggressive in-transit metastatic disease and recurrent nodal disease. The patient was treated with systemic immunotherapy alone, which not only prompted the progressive nodal metastases to regress, but also resulted in a complete response of the in-transit disease. This situation is previously undescribed in the medical literature.

The maritime dimension defense strategy model is a part of the Archipelago Marine Defense Strategy, referring to the dynamics or developments in the strategic environment and the capabilities of available national resources. In carrying out an assessment of the defense strategy of the archipelagic nation's sea dimension, it is determined by the influence and interaction of interrelationships between balancing aspects of Naval Forces and Integrated Fleet Weapons Systems (SSAT) with Threat aspects as a complex system, so an analysis is needed to get a value on the assessment defense strategy of the maritime dimension of the archipelagic state, which consists of aspects of developing the strength of the Navy and aspects of Potential Threats. So it needs to be compiled in a dynamic model that can represent a value in the assessment of the marine defense dimension of the archipelagic nation which is projected based on the time dimension up to the next 15 years. In this research, the researchers compiled a system dynamic model approach to obtain an assessment of the value of each variable and sub-variable. The results of the formulation and simulation model on the assessment of the sea dimension defense strategy, obtained values based on the following strategic scenarios: (1) Fleet In Being defense strategy at an index value of 5.72, (2) Blockade defense scenario 5.72, (3) Defense scenario Decesive Battle 5.73, (4) combined scenario between fleet in being and blockade 5.72, (5) combined scenario of fleet in being and decesive battle 5.78, (6) combination scenario of blocakde and decesive battle 5.73 and value sea defense based on current SSAT capabilities in the 15th year of 5.9, included in the alert category/quite safe.

IntroductionThe use of mobile device presents both benefits and barriers. However, studies into the use of technology in fieldwork often focus only on either practitioner views or student views. Digital field notebooks (DFNs) are one-way mobile devices can be used to enhance fieldwork. Yet their use is limited to Geography, Earth and Environmental Science (GEES) disciplines, with students often playing a passive role during the development of DFNs. This research reports on the development of a DFN to enhance bioscience fieldwork in Higher Education (HE).MethodsUsing interviews, focus groups, and survey methods we investigated how both fieldwork practitioners and learners view the role of technology in the field. Working in partnership with students, we explored their experiences of using a DFN during fieldwork. Feedback was utilized to make changes to the DFN to support its integration within bioscience fieldwork.ResultsOverall, valuable developments related to content, technology, and pedagogy were made to the DFN, identifying value in a co-creation process. For example, students suggested the role of the DFN as a collaborative tool where individual entries were collated together. A workflow schematic and case study are presented for how a DFN can be used during bioscience fieldwork in HE.DiscussionAlthough students identified place connection and the development of reflective practice as particular affordances, students did not identify any digital skill development opportunities when using the DFN. Additionally, although students suggested the DFN was easy to use, barriers remain for students in using a DFN. We suggest further research on the complex issues of permission and perceptions of value of mobile device use during fieldwork. Additionally, more explicit reference to digital skill developments should be made when using a DFN.

Abstract Background The notion that all acute hip fractures are a surgical entity requiring either surgical fracture fixation or hip replacement represents a historic dogma, particularly within the orthopaedic community of the United States. The present study from a European regional trauma center was designed to challenge the notion that stable and undisplaced femoral neck fractures represent an absolute indication for surgical management. Methods The purpose of this study was to investigate the hypothesis that stable and undisplaced femoral neck fractures of the Garden types 1 and 2 can be safely managed nonoperatively. A retrospective observational cohort study was carried out at a regional orthopaedic trauma center in Germany from January 1, 2016 to June 30, 2021. The inclusion criteria specified patients older than 18 years suffering a

Rapid urban expansion in Sub-Saharan Africa is a challenging policy problem with few demonstrated solutions. An approach for managing rapid urbanization resulted in considerable changes in planning strategies in cities in Ethiopia. An initiative from 2013 to 2016 created organizational capacities and capabilities. An external consultant facilitated knowledge exchange, but left the major planning activities to the public sector bodies. Local technical staff and political leaders were trained to create and implement plans for the next 30 years of urban growth in their cities. The paper describes the role of knowledge exchange in empowering local government officials to implement the approach. It outlines the approach itself and then describes the process of knowledge exchange and the challenges and successes that resulted. 'Practice relevance' Urban planning and expansion require forethought as well as sustained effort for delivery over time. A successful intervention is presented together with a core factor of knowledge exchange. The role of the external consultant team was unusual: to provide a limited amount of input data and instead focus on guidance and advice. The significance of simple ideas is their ease of sharing amongst policymakers as a strategy for producing local ownership. Diffusion and dissemination of good ideas often stops after a single expensive and time-consuming pilot project, in part because complexity prevents the participants from attaining expertise to spread the idea without external support. Urban expansion planning is framed as an example of a planning approach that emphasized knowledge exchange. The conclusions could also apply to the development of any future planning techniques that depend on local implementation and uptake.

Background Children undergoing surgery and their parents are at risk of developing post-traumatic stress reactions. We systematically reviewed the literature to understand the prevalence of this issue, as well as potential risk factors.Methods We conducted a systematic review and meta-analysis, using PubMed, PsycInfo, Web of Science and Google Scholar, with searches conducted in February 2021. Papers were included if they measured post-traumatic stress in children and/or parents following paediatric surgery and were excluded if they did not use a validated measure of post-traumatic stress. Data were extracted from published reports.Findings Our search yielded a total of 1672 papers, of which 16 met our inclusion criteria. In meta-analysis, pooled studies of children estimated an overall prevalence of 16% meeting criteria for post-traumatic stress disorder post surgery (N=187, 95% CI 5% to 31%, I2=80%). After pooling studies of parents, overall prevalence was estimated at 23% (N=1444, 95% CI 16% to 31%, I2=91%). Prevalence rates were higher than those reported in the general population. Risk factors reported within studies included length of stay, level of social support and parental mental health.Interpretation There is consistent evidence of traumatic stress following surgery in childhood which warrants further investigation. Those delivering surgical care to children would benefit from a raised awareness of the potential for post-traumatic stress in their patients and their families, including offering screening and support.

Abstract Background After viral fusion with the cell membrane, the conical capsid of HIV-1 disassembles by a process called uncoating. Previously we have utilized the CsA washout assay, in which TRIM-CypA mediated restriction of viral replication is used to detect the state of the viral capsid, to study the kinetics of HIV-1 uncoating in owl monkey kidney (OMK) and HeLa cells. Here we have extended this analysis to the human microglial cell lines CHME3 and C20 to characterize uncoating in a cell type that is a natural target of HIV infection. Methods The CsA washout was used to characterize uncoating of wildtype and capsid mutant viruses in CHME3 and C20 cells. Viral fusion assays and nevirapine addition assays were performed to relate the kinetics of viral fusion and reverse transcription to uncoating. Results We found that uncoating initiated within the first hour after viral fusion and was facilitated by reverse transcription in CHME3 and C20 cells. The capsid mutation A92E did not significantly alter uncoating kinetics. Viruses with capsid mutations N74D and E45A decreased the rate of uncoating in CHME3 cells, but did not alter reverse transcription. Interestingly, the second site suppressor capsid mutation R132T was able to rescue the uncoating kinetics of the E45A mutation, despite having a hyperstable capsid. Conclusions These results are most similar to previously observed characteristics of uncoating in HeLa cells and support the model in which uncoating is initiated by early steps of reverse transcription in the cytoplasm. A comparison of the uncoating kinetics of CA mutant viruses in OMK and CHME3 cells reveals the importance of cellular factors in the process of uncoating. The E45A/R132T mutant virus specifically suggests that disrupted interactions with cellular factors, rather than capsid stability, is responsible for the delayed uncoating kinetics seen in E45A mutant virus. Future studies aimed at identifying these factors will be important for understanding the process of uncoating and the development of interventions to disrupt this process.

Termite mounds are fascinating because of their intriguing composition of numerous geometric shapes and materials. However, little is known about these structures, or of their functionalities. Most research has been on the basic composition of mounds compared with surrounding soils. There has been some targeted research on the thermoregulation and ventilation of the mounds of a few species of fungi-growing termites, which has generated considerable interest from human architecture. Otherwise, research on termite mounds has been scattered, with little work on their explicit properties.This review is focused on how termites design and build functional structures as nest, nursery and food storage; for thermoregulation and climatisation; as defence, shelter and refuge; as a foraging tool or building material; and for colony communication, either as in indirect communication (stigmergy) or as an information channel essential for direct communication through vibrations (biotremology).Our analysis shows that systematic research is required to study the properties of these structures such as porosity and material composition. High resolution computer tomography in combination with nonlinear dynamics and methods from computational intelligence may provide breakthroughs in unveiling the secrets of termite behaviour and their mounds. In particular, the examination of dynamic and wave propagation properties of termite-built structures in combination with a detailed signal analysis of termite activities is required to better understand the interplay between termites and their nest as superorganism. How termite structures serve as defence in the form of disguising acoustic and vibration signals from detection by predators, and what role local and global vibration synchronisation plays for building are open questions that need to be addressed to provide insights into how termites utilise materials to thrive in a world of predators and competitors.

This paper describes an exact branch-and-cut (B&C) algorithm for the split delivery vehicle routing problem. The underlying model is based on a previously proposed two-index vehicle flow formulation that models a relaxation of the problem. We dynamically separate two well-known classes of valid inequalities, namely capacity and connectivity cuts, and use an in-out algorithm to improve the convergence of the cutting phase. We generate no-good cuts from feasible integer solutions to the relaxation using a recently proposed single-commodity flow formulation in the literature. The exact methodology is complemented by a very effective adaptive large neighborhood search (ALNS) heuristic that provides high-quality upper bounds to initiate the B&C algorithm. Key ingredients in the design of the heuristic include the use of a tailored construction algorithm, which can exploit the situation in which the ratio of the number of customers to the minimum number of vehicles needed is low, and the use of a route-based formulation to improve the solutions found before, during, and after the ALNS procedure. An earlier version of this work was submitted to the DIMACS (Center for Discrete Mathematics and Theoretical Computer Science) implementation challenge, where it placed third. On sets of well-known benchmark instances for limited and unlimited fleet variants of the problem, we demonstrate that the heuristic provides very competitive solutions, with respective average gaps of 0.19% and 0.18% from best-known values. Furthermore, the exact B&C framework is also highly competitive with state-of-the-art methods, providing solutions with an average optimality gap of 1.82%. History: This paper has been accepted for the Transportation Science Special Section on DIMACS Implementation Challenge: Vehicle Routing Problems. Supplemental Material: The online appendices are available at https://doi.org/10.1287/trsc.2022.0353. [ABSTRACT FROM AUTHOR]