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Background: Human endogenous retrovirus K (HERV-K) belongs to a family of endogenous retroviruses that are present in our genome with similarities to present day exogenous retroviruses. HERV-K, like other endogenous retroviruses, is transmitted vertically in a Mendelian fashion through the human genome. This virus can express several proteins but our knowledge of HERV-K expression in human cancers is mainly limited to the envelope (Env) protein. Elevated HERV-K env protein expression has been shown in breast cancer both in in vitro and in vivo studies. Previous work from this laboratory has shown increased HERV-K expression in blood is predictive of a prostate cancer diagnosis. Aims & Experimental Approach: This project aimed to decipher whether individual HERV-K proteins (Env and Gag) display differential association with histological type, molecular subtype and patient outcomes in an Irish cohort of triple negative breast cancer patients (n=177). Additionally we aimed to assess the impact of HERV-K targeting shRNA mediated knockdown on TNBC characteristics including cell migration, invasion and proliferative capacity in 2D and 3D cell culture models. RNA seq and bioinformatics analysis was performed to identify key molecular processes regulated by HERV-K in TNBC. Results: HERV-K Env expression showed a trend towards an association with poor survival in TNBC (Log rank test, p=0.105), while HERV-K Gag was not found to be associated with survival. HERV-K Env positive metastatic patients had an increased involvement of the bone and lungs compared to HERV-K Env negative patients, while HERV-K gag positive patients showed reduced liver metastasis involvement. Knockdown of HERV-K in TNBC cell lines MDA-MB-231 and MDA-MB-468 reduced their proliferative, migratory and invasive potential. Preliminary screens using a cancer drug target array shows significantly reduced expression of HDAC4, a regulator of cell growth and the anti-apoptotic protein. GSEA analysis of RNAseq data from MDA-MB-231 HERV-K shRNA knockdown demonstrated enrichment for genes associated with both the Charafe downregulated in Luminal A versus Mesenchymal gene signature (p= 5.14x10-133), and the Charafe downregulated in Luminal A versus Basal gene signature (p= 7.03x10-110), indicating that HERV-K may play an important role in mesenchymal and basal phenotype TNBC. Additionally pathway analysis points toward a role in the regulation of many different pathways and cellular process, including focal adhesion (p= 9.77x10-7), cellular senescence (p= 7.63x10-7) and viral signalling pathways (p= 6.86x10-14). Discussion: Reduced rates of migration, invasion and proliferation in HERV-K knockdowns points towards the essential role of HERV-K in tumorigenesis and metastasis. HERV-K knockdown also modulated key gene expression signatures traditionally associated with the basal and mesenchymal phenotypes in breast cancer. Taken together, our findings indicate that HERV-K may be a useful molecular target for the treatment of TNBC. Citation Format: Sharon A Glynn, Dibyangana Bhattacharyya, Shauna Lambe, Emma Kerr, Simon McDade, Faizan H Khan, Eoin Dervan, Feng Wang-Johanning, Sean Hynes, Grace Callagy. Human endogenous retrovirus-K (HERV-K) is aberrantly expressed in triple negative breast cancer (TNBC) and associated with increased distant metastasis: Impact of HERV-K knockdown on gene expression patterns and invasive potential of mesenchymal TNBC [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-06-05.

Atmospheric mass density (AMD) plays a vital role in the drag calculation for space objects in low Earth orbit (LEO). Many empirical AMD models have been developed and used for orbit prediction and...

An increasing number of objects are being launched into low-Earth orbit. Consequently, to avoid the possibility of future in-orbit collisions space object removal techniques are receiving attention. As one of the most developed techniques, drag augmentation is increasingly being considered as an option for end-of-mission removal of objects from low-Earth orbit. This paper highlights a common misconception around drag augmentation: although it can be used to reduce de-orbit time, when used inappropriately it can increase the volume swept by an object and, thus, increase the occurrence risk of collision with another space object. Knowingly ignoring this increased risk of collisions could leave spacecraft operators, and consequently their responsible state party, open to liability risk. By investigating the volume swept and de-orbit lifetime, a strategy of delayed deployment is proposed as a compromise between reducing volume swept and time to de-orbit. However, this increases system complexity and, likely, cost.

IMPORTANCE: The psychological symptoms associated with having a family member admitted to the intensive care unit (ICU) during the COVID-19 pandemic are not well defined. OBJECTIVE: To examine the prevalence of symptoms of stress-related disorders, primarily posttraumatic stress disorder (PTSD), in family members of patients admitted to the ICU with COVID-19 approximately 90 days after admission. DESIGN, SETTING, AND PARTICIPANTS: This prospective, multisite, mixed-methods observational cohort study assessed 330 family members of patients admitted to the ICU (except in New York City, which had a random sample of 25% of all admitted patients per month) between February 1 and July 31, 2020, at 8 academic-affiliated and 4 community-based hospitals in 5 US states. EXPOSURE: Having a family member in the ICU with COVID-19. MAIN OUTCOMES AND MEASURES: Symptoms of PTSD at 3 months, as defined by a score of 10 or higher on the Impact of Events Scale 6 (IES-6). RESULTS: A total of 330 participants (mean [SD] age, 51.2 [15.1] years; 228 [69.1%] women; 150 [52.8%] White; 92 [29.8%] Hispanic) were surveyed at the 3-month time point. Most individuals were the patients’ child (129 [40.6%]) or spouse or partner (81 [25.5%]). The mean (SD) IES-6 score at 3 months was 11.9 (6.1), with 201 of 316 respondents (63.6%) having scores of 10 or higher, indicating significant symptoms of PTSD. Female participants had an adjusted mean IES-6 score of 2.6 points higher (95% CI, 1.4-3.8; P

Background: Characterizations of sharks-microbe systems in wild environments have outlined patterns of species-specific microbiomes; however, whether captivity affects these trends has yet to be determined. We used high-throughput shotgun sequencing to assess the epidermal microbiome belonging to leopard sharks (Triakis semifasciata) in captive (Birch Aquarium, La Jolla California), semi-captive (Results: Here we report captive environments do not drive microbiome composition of T. semifasciata to significantly diverge from wild counterparts as life-long captive sharks maintain a species-specific epidermal microbiome resembling those associated with semi-captive and wild populations. Major taxonomic composition shifts observed were inverse changes of top taxonomic contributors across captive duration, specifically an increase of Pseudoalteromonadaceae and consequent decrease of Pseudomonadaceae relative abundance as T. semifasciata increased duration in captive conditions. Moreover, we show captivity did not lead to significant losses in microbial α-diversity of shark epidermal communities. Finally, we present a novel association between T. semifasciata and the Muricauda genus as MAGs revealed a consistent relationship across captive, semi-captive, and wild populations. Conclusions: Our report illustrates the importance of conservation programs for coastal fishes as epidermally-associated microbes of near-shore shark species do not suffer detrimental impacts from long or short-term captivity. Our findings also expand on current understanding of shark epidermal microbiomes, explore the effects of ecologically different scenarios on benthic shark microbe associations, and highlight novel microbial associations that are consistent across captive gradients.

Background/Aims This article details how a patient-reported outcome measure (PROM), termed PROM-CR1, was tested for acceptability, validity and test-retest reliability at the end of an outpatient cardiac rehabilitation programme. Methods PROM-CR1 was completed by 138 service users (mean age 66.95 years, range 42–94 years; 115 males, 23 females; with a range of cardiac diagnoses), who used the tool at home twice: once at the end of the outpatient cardiac rehabilitation programme and 1 week later. Results PROM-CR1 demonstrated good acceptability, construct and concurrent validity, and test-retest reliability. The construct validity analysis highlighted that one item required removal from the PROM-CR1. Conclusions A finalised 30-item version of the tool will now be widely disseminated and further evaluated within cardiac rehabilitation clinical practice.

Background/Aims A 40-item first draft PROM (PROM-CR1) had previously been developed for use in cardiac rehabilitation. This article details how PROM-CR1 was tested for item relevance, and for acceptability and validity when used at an initial CR outpatient appointment. Methods Cardiac rehabilitation staff rated the relevance of all 40 items. The PROM-CR1 was then piloted across 185 service users (mean age 67.24 years; 147 males/40 females; referred with a range of cardiac diagnoses) who completed the tool at their initial cardiac rehabilitation outpatient appointment. Results Analyses of item relevance and construct validity flagged nine items requiring removal from the tool; all other items and scores performed well in these tests. PROM-CR1 demonstrated good concurrent and discriminant validity, and its performance improved with the flagged items removed. Conclusions The 31-item version of PROM-CR1 will be re-tested when applied at the end of outpatient CR and refined into a finalised tool (PROM-CR) for clinical practice.

Atmospheric drag, as one of the largest non-gravitational perturbations in low Earth orbit (LEO), can dramatically decay the orbit of LEO satellites with both secular and periodic effects. Hence, it plays a critical role in orbit prediction related products, and research on orbit determination, orbital uncertainty propagation and collision avoidance. Although many empirical thermospheric mass density (TMD) models have been proposed in the past few decades, precise determination of atmospheric drag is still a challenging task. In order to give a comprehensive review of the current empirical TMD models, focusing on their impact on orbital dynamics, this review summarises and investigates the most representative classes of models, including the Jacchia, Mass Spectrometer Incoherent Scatter (MSIS), Jacchia-Bowman (JB), and Drag Temperature Model (DTM). Twelve representative models are selected for further comparison in terms of spatial variations and assessing their ability to capture complex features, e.g., equatorial mass density anomaly (EMA). Further validation is done with accelerometer-derived TMD from LEO satellites. The results show that only DTM2013 can capture the EMA feature and the drag coefficient calculated by physical models used in the TMD estimation may be underestimated. The performance of these models in orbit prediction is comprehensively evaluated under different solar and geomagnetic conditions. JB2008 and DTM2013 outperform the other selected models during low and high solar activity. Standard deviation is found to be less affected by the bias in the accelerometer- and model-derived TMD, than mean value and root-mean-square error. The coupling effect between the TMD and ballistic coefficient, and the potential directions for future efforts in TMD modelling are also discussed.

Background: A Scotland-wide government scoping exercise identified the need for a new patient-reported outcome measure (PROM) suitable for the wide range of diagnostic groups now accessing cardiac rehabilitation (CR). Aim: This paper describes the initial steps underpinning development of the item bank for a first draft tool (PROM–CR1). Methods: A literature review of existing tools was undertaken to guide a qualitative data collection methodology involving 19 CR staff and 22 service users. Results: Four conceptual ideas for health/quality of life were identified from the literature review: general health; physical; social; and psychological. Three key qualitative themes, largely reflective of literature review findings, were identified: expectations and entitlement; adjustment and acceptance; and control and choice. Future directions: These data will be combined to form PROM-CR1's initial item bank, which will be piloted with staff and service users and refined to generate a finalised tool (PROM–CR) for use in clinical practice.

A new parameter is introduced, termed the density index, which enables the solar activity cycle to be captured in a new analytical atmospheric density model. Consequentially, a new solar activity model is developed that uses a single independent variable per solar cycle to describe the solar activity across that cycle, as indicated by the F10.7 index. These models are combined and applied to a well-known general perturbations method for satellite orbit lifetime analysis, which is first modified using modern mathematical tools to remove simplifications in the derivation. Validation against historical data shows an improvement in orbit lifetime estimates from an average error of 50.44 percent with a standard deviation of 24.96 percent, to an average error of 3.46 percent with a standard deviation of 3.25 percent. Furthermore, the new method with applied atmospheric and solar activity models is found to compare favorably against other general and special perturbations methods, including third party, and commercial software, the most accurate of which was found to have an average error of 6.63 percent and standard deviation of 7.00 percent. A case study, the UKube-1 spacecraft, is presented and it is found that the spacecraft was inserted into an orbit 54km lower than required to comply with best-practice guidelines, and that with 1σ confidence its orbit will decay in June 2028 ± 2 years, and June 2028 ± 4 months if the next solar cycle is an average magnitude cycle.

Introduction: Older adults comprise an increasing proportion of emergency general surgery (EGS) admissions and face high morbidity and mortality. We created a geriatric surgical service with geriatric and palliative expertise to mitigate risks of hospitalization most hazardous to older patients. In this study, we identified geriatric surgical service interventions most relevant to EGS patients. Methods: We conducted a retrospective chart review of patients >75 years admitted to the EGS service at our urban tertiary care hospital with a score >3 by the FRAIL scale, a five-point frailty screening instrument, or history of dementia. The geriatric surgical service, led by a dually-board certified geriatric and palliative care specialist, consulted on these patients from January 2020-January 2021;a hiatus was taken for the COVID-19 pandemic. Consults included a comprehensive geriatric assessment and calculated a modified Rockwood Frailty Index. Hospital admission characteristics and consultation components were collected via chart review. Results: Forty patients were evaluated (median age 82 years (IQR 78-89), 55.0% female). The most common admission diagnosis was small bowel obstruction (32.5%). 62.5% of patients underwent >1 surgical procedure. Median time to geriatric consult from admission was 3 days (IQR 1.0-4.3). By Frailty Index, 58% were moderately or severely frail. Interventions included medication changes (97.5%), symptom management (82.5%), delirium prevention and management (65.0%), mobility and function recommendations (65.0%), serious illness conversations (55.0%), and code status change (17.5%). Conclusion: Geriatric service involvement identifies and addresses a high burden of both geriatric and palliative care needs in older adult EGS patients.

This work proposes a novel method for the deployment of a constellation of nano-satellites into Low Earth Orbit by using carrier vehicles to deliver the nano-satellites into the required orbit positions. The analytical solution presented allows for rapid exploration of the design space and a direct optimisation of the deployment strategy to minimise the time for complete constellation deployment. Traditionally, the deployment of satellite constellations requires numerous launches – at least one per orbital plane – which can be costly. Launching as a secondary payload may offer significant cost reductions, but this comes at the price of decreased control over the launch schedule and final orbit parameters. The analytical method presented here allows for the optimal positioning of the orbit planes of the constellation to be determined and the minimum time for deployment determined as a function of the manoeuvre ΔV. The effect of atmospheric drag on the manoeuvre propellant cost is also considered to ensure a realistic deployment scenario. A case study considering three constellation designs is presented which compares the cost of deployment using traditional launch methods with that of deploying the constellation using carrier vehicles. The results of this study show a significant reduction in cost when using the carrier vehicles on a dedicated launch, compared with launching the satellites individually. Most significantly, the launch cost when using carrier vehicles is primarily determined by the total number of satellites in the constellation, rather than the number of orbital planes. Thus, the carrier vehicle deployment strategy would allow for constellations with a large number of planes to be deployed for a fraction of the equivalent cost if traditional launch methods were used.

A general perturbations method for orbit lifetime analysis is extended to include an analytical non-spherically-symmetrical atmospheric density model. This improvement allows the method to be applied with confidence to highly inclined orbits and special cases such as sun-synchronous orbits where the inclusion of the effects of atmospheric oblateness and the diurnal bulge will be particularly significant. These improvements can be applied to any general perturbations model for lifetime analysis. Using a case study of a sun-synchronous satellite a comparison is drawn between the original and improved methods, showing that by capturing the effects of a non-spherically-symmetrical atmosphere the orbit lifetime predicted could be up to 7% longer or 10% shorter than when using the spherically-symmetrical model. Also notable is the difference between the orbit lifetime predictions made using the spherically-symmetrical model derived from different data sets; for the case study this was approximately a third of the orbit lifetime.

Metacognitive beliefs about the benefits of rumination are associated with rumination and depression; however, the direction of these relationships remains unclear. Two experiments examined whether individuals with high positive beliefs about rumination engaged in more rumination following a laboratory-based stressor than individuals with low levels of such beliefs. In Study 1, participants with high levels of positive beliefs reported more rumination following receipt of negative feedback on a forced-failure anagram task. In Study 2, participants with high levels of positive beliefs reported more rumination compared to participants with low levels of positive beliefs, regardless of whether they received negative feedback, positive feedback or no feedback on their performance. Our findings demonstrate the importance of positive beliefs about rumination, and highlight the utility of treatment approaches that aim to reduce rumination by targeting such unhelpful metacognitive beliefs. Copyright © 2010 John Wiley & Sons, Ltd.

We report on field annealing effects in spin valves with an IrMn pinning layer and spin valves with a synthetic antiferromagnet. The exchange bias field and magnetoresistance of spin valves with an IrMn∕CoFe bilayer at the bottom improve drastically upon annealing in large magnetic fields. The evolution of the exchange bias field with annealing field strength shows a rapid increase up to an applied field of 0.5 T, which is followed by a more gradual improvement up to an annealing field of 5.5 T. The increase of the exchange bias field in large magnetic fields indicates that the interfacial spin structure of the IrMn layer is directly influenced by the annealing field strength.

One major source of new space debris are spacecraft (S/C) that are not removed from orbit after the end of their operational lifetime. Many regulations (e.g. ISO 24113) require the removal of S/C at the end of operation - known as Post-Mission-Disposal (PMD) - with a compliance rate of 90% to ensure that S/C do not become a new source of space debris. An analysis performed by ESA shows that the success rate of PMD in 2013 was in the range of about 50%-60%. The goal of TeSeR (Technology for Self-Removal) is to take the first step towards the development of a costefficient, but highly reliable PMD module. This PMD module is to be attached to the S/C on ground and it shall ensure the PMD of the S/C at the end of the operational lifetime. This PMD module shall be scalable and flexible, thus, enabling the PMD of any future S/C in an Earth orbit. Ultimately, the gap between the required 90% PMD success rate and the current success rate can be closed. The technological enhancements and developments required for successful PMD are addressed and analysed in TeSeR. The project’s primary aims are  to develop, manufacture and test an on-ground prototype of the PMD module,  to develop three different removal subsystems (solid propulsion, electro-dynamical systems and deployable structures) for easy plug-in/plug-out implementation to the PMD module. This is the first step to demonstrate the main aspects of such a PMD module and the required main technologies. The technical activities are supported by non-technical tasks, e.g. investigation of legal issues relating to a PMD module, execution of a market study and consideration of this technology as a leverage to advance ISO norms. This double tracked approach ensures that the technological developments are embedded into the needs of the space community right from the start. Up to now the prototypes of the three removal subsystems have been developed, manufactured and tested with a common interface for implementation into the PMD module prototype. The PMD module prototype will be manufactured until summer 2018. Afterwards the removal subsystems will be integrated via the same interface. Airbus is the coordinator (and potential launch customer) of TeSeR. The project is conducted together with 10 notable institutes and companies from all across Europe with experts who have been working in the space debris issue for many years.