Search

Precision Livestock Farming (PLF) technologies can now allow ethologists to continuously monitor the behaviors of large numbers of animals over extended periods of observation. This creates new opportunities to study the behavioral dynamics of livestock in working farm environments, but also raises new methodological challenges. Large and densely sampled sensor datasets can contain a range of complex deterministic and stochastic structures that may difficult to fully accommodate in conventional model-based approaches. This thesis will explore the utility of model-free approaches to recovering complex behavioral patterns from within and across PLF data streams using unsupervised machine learning and information theoretic approaches. Chapter one will explore how data mechanics, an iterative hierarchical clustering algorithm, may be used to leverage the intrinsic behavioral codependences of socially housed animals to recover complex temporal patterns in the order in which cows enter the parlor to be milked, even when the environmental or managerial changes eliciting changes in queueing patterns are not recorded. Chapter two will introduce ensemble mimicry approaches, wherein minimally parametric simulation strategies may be employed to mimic the complex and often codependent sources of measurement error often found in PLF data streams, and demonstrate how this information may be infused into standard hierarchical clustering approaches to recover the most reliable patterns in overall time budgets. A model-free approach to recovering complex nonlinear bivariate associations between data streams is also developed using information theoretic approaches. Chapter three extends the data mechanics framework to recover temporal nonstationarity in multivariate records using tensor data structures to explore systematic patterns in daily time budget records. Finally, chapter four will explore model free approaches to quantifying the relative plasticity in biological and behavioral

Contains fulltext : 287044.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 287044.pdf (Publisher’s version ) (Open Access)

Background Given the recent detection of TTX in bivalve molluscs but the absence of a full collaborative validation study for TTX determination in a large number of shellfish samples, interlaboratory assessment of method performance was required to better understand current capabilities for accurate and reproducible TTX quantitation using chemical and immunoassay methods. Objective The aim was to conduct a collaborative study with multiple laboratories, using results to assess method performance and acceptability of different TTX testing methods Methods Homogenous and stable mussel and oyster materials were assessed by participants using a range of published and in-house detection methods to determine mean TTX concentrations. Data was used to calculate recoveries, repeatability and reproducibility, together with participant acceptability z-scores. Results Method performance characteristics were good, showing excellent sensitivity, recovery and repeatability. Acceptable reproducibility was evidenced by HorRat values for all LC-MS/MS and ELISA methods being less than the 2.0 limit of acceptability. Method differences between the LC-MS/MS participants did not result in statistically-different results. Method performance characteristics compared well with previously-published single-laboratory validated methods and no statistical difference was found in results returned by ELISA in comparison with LC-MS/MS. Conclusions The results from this study demonstrate that current LC-MS/MS methods and the ELISA are on the whole capable of sensitive, accurate and reproducible TTX quantitation in shellfish. Further work is recommended to expand the number of laboratories testing ELISA and to standardise an LC-MS/MS protocol to further improve interlaboratory precision. Highlights Multiple mass spectrometric methods and a commercial ELISA have been successfully assessed through collaborative study, demonstrating excellent performance.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has an established role for the diagnosis of clinically significant prostate cancer (sPCa). The PRIMARY trial demonstrated that [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) was associated with a significant improvement in sensitivity and negative predictive value for sPCa detection. OBJECTIVE: To demonstrate that addition of prostate-specific membrane antigen (PSMA) radioligand PET/CT will enable some men to avoid transperineal prostate biopsy without missing sPCa, and will facilitate biopsy targeting of PSMA-avid sites. DESIGN, SETTING, AND PARTICIPANTS: This multicentre, two-arm, phase 3, randomised controlled trial will recruit 660 participants scheduled to undergo biopsy. Eligible participants will have clinical suspicion of sPCa with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 2 and red flags, or a PI-RADS score of 3 on mpMRI (PI-RADS v2). Participants will be randomised at a 1:1 ratio in permuted blocks stratified by centre. The trial is registered on ClinicalTrials.gov as NCT05154162. INTERVENTION: In the experimental arm, participants will undergo pelvic PSMA PET/CT. Local and central reviewers will interpret scans independently using the PRIMARY score. Participants with a positive result will undergo targeted transperineal prostate biopsies, whereas those with a negative result will undergo prostate-specific antigen monitoring alone. In the control arm, all participants undergo template transperineal prostate biopsies. Participants will be followed for subsequent clinical care for up to 2 yr after randomisation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: sPCa is defined as Gleason score 3 + 4 (≥10%) = 7 disease (grade group 2) or higher on transperineal prostate biopsy. Avoidance of transperineal prostate biopsy will be measured at 6 mo from randomisation. The primary endpoints will be analysed on an intention-to-treat basis. CONCLUSIONS: Pat

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has an established role for the diagnosis of clinically significant prostate cancer (sPCa). The PRIMARY trial demonstrated that [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) was associated with a significant improvement in sensitivity and negative predictive value for sPCa detection. OBJECTIVE: To demonstrate that addition of prostate-specific membrane antigen (PSMA) radioligand PET/CT will enable some men to avoid transperineal prostate biopsy without missing sPCa, and will facilitate biopsy targeting of PSMA-avid sites. DESIGN, SETTING, AND PARTICIPANTS: This multicentre, two-arm, phase 3, randomised controlled trial will recruit 660 participants scheduled to undergo biopsy. Eligible participants will have clinical suspicion of sPCa with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 2 and red flags, or a PI-RADS score of 3 on mpMRI (PI-RADS v2). Participants will be randomised at a 1:1 ratio in permuted blocks stratified by centre. The trial is registered on ClinicalTrials.gov as NCT05154162. INTERVENTION: In the experimental arm, participants will undergo pelvic PSMA PET/CT. Local and central reviewers will interpret scans independently using the PRIMARY score. Participants with a positive result will undergo targeted transperineal prostate biopsies, whereas those with a negative result will undergo prostate-specific antigen monitoring alone. In the control arm, all participants undergo template transperineal prostate biopsies. Participants will be followed for subsequent clinical care for up to 2 yr after randomisation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: sPCa is defined as Gleason score 3 + 4 (≥10%) = 7 disease (grade group 2) or higher on transperineal prostate biopsy. Avoidance of transperineal prostate biopsy will be measured at 6 mo from randomisation. The primary endpoints will be analysed on an intention-to-treat basis. CONCLUSIONS: Pat

Community-based conservation can support livelihoods and biodiversity, while reinforcing local and Indigenous values, cultures, and institutions. Its delivery can help address cross-cutting global challenges, such as climate change, conservation, poverty, and food security. Therefore, understanding trends in community-based conservation is pertinent to setting and implementing global goals. We undertook a horizon scan to prioritize 15 emerging threats and opportunities expected to impact the future effectiveness of community-based conservation. Topics relate to global biodiversity policy; human rights; shifting human geography; inclusion, diversity, equity, and access; conservation finance and income; and economic reforms. Our findings offer guidance on strengthening community-based conservation to achieve global environmental and development goals.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has an established role for the diagnosis of clinically significant prostate cancer (sPCa). The PRIMARY trial demonstrated that [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) was associated with a significant improvement in sensitivity and negative predictive value for sPCa detection. OBJECTIVE: To demonstrate that addition of prostate-specific membrane antigen (PSMA) radioligand PET/CT will enable some men to avoid transperineal prostate biopsy without missing sPCa, and will facilitate biopsy targeting of PSMA-avid sites. DESIGN, SETTING, AND PARTICIPANTS: This multicentre, two-arm, phase 3, randomised controlled trial will recruit 660 participants scheduled to undergo biopsy. Eligible participants will have clinical suspicion of sPCa with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 2 and red flags, or a PI-RADS score of 3 on mpMRI (PI-RADS v2). Participants will be randomised at a 1:1 ratio in permuted blocks stratified by centre. The trial is registered on ClinicalTrials.gov as NCT05154162. INTERVENTION: In the experimental arm, participants will undergo pelvic PSMA PET/CT. Local and central reviewers will interpret scans independently using the PRIMARY score. Participants with a positive result will undergo targeted transperineal prostate biopsies, whereas those with a negative result will undergo prostate-specific antigen monitoring alone. In the control arm, all participants undergo template transperineal prostate biopsies. Participants will be followed for subsequent clinical care for up to 2 yr after randomisation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: sPCa is defined as Gleason score 3 + 4 (≥10%) = 7 disease (grade group 2) or higher on transperineal prostate biopsy. Avoidance of transperineal prostate biopsy will be measured at 6 mo from randomisation. The primary endpoints will be analysed on an intention-to-treat basis. CONCLUSIONS: Pat

Background Given the recent detection of TTX in bivalve molluscs but the absence of a full collaborative validation study for TTX determination in a large number of shellfish samples, interlaboratory assessment of method performance was required to better understand current capabilities for accurate and reproducible TTX quantitation using chemical and immunoassay methods. Objective The aim was to conduct a collaborative study with multiple laboratories, using results to assess method performance and acceptability of different TTX testing methods Methods Homogenous and stable mussel and oyster materials were assessed by participants using a range of published and in-house detection methods to determine mean TTX concentrations. Data was used to calculate recoveries, repeatability and reproducibility, together with participant acceptability z-scores. Results Method performance characteristics were good, showing excellent sensitivity, recovery and repeatability. Acceptable reproducibility was evidenced by HorRat values for all LC-MS/MS and ELISA methods being less than the 2.0 limit of acceptability. Method differences between the LC-MS/MS participants did not result in statistically-different results. Method performance characteristics compared well with previously-published single-laboratory validated methods and no statistical difference was found in results returned by ELISA in comparison with LC-MS/MS. Conclusions The results from this study demonstrate that current LC-MS/MS methods and the ELISA are on the whole capable of sensitive, accurate and reproducible TTX quantitation in shellfish. Further work is recommended to expand the number of laboratories testing ELISA and to standardise an LC-MS/MS protocol to further improve interlaboratory precision. Highlights Multiple mass spectrometric methods and a commercial ELISA have been successfully assessed through collaborative study, demonstrating excellent performance.

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating., Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 71

This article discusses the legal implications of a novel phenomenon, namely, digital reincarnations of deceased persons, sometimes known as post-mortem avatars, deepfakes, replicas, holographs, or chatbots. To elide these multiple names, we use the term 'ghostbots'. The piece is an early attempt to discuss the potential social and individual harms, roughly grouped around notions of privacy (including post-mortem privacy), property, personal data and reputation, arising from ghostbots, how they are regulated and whether they need to be adequately regulated further. For reasons of space and focus, the article does not deal with copyright implications, fraud, consumer protection, tort, product liability, and pornography laws, including the non-consensual use of intimate images (‘revenge porn’). This paper focuses on law, although we fully acknowledge and refer to the role of philosophy and ethics in this domain. We canvas two interesting legal developments with implications for ghostbots, namely, the proposed EU Artificial Intelligence (AI) Act and the 2021 New York law amending publicity rights to protect the rights of celebrities whose personality is used in post-mortem ‘replicas’. The latter especially evidences a remarkable shift from the norm we have chronicled in previous articles of no respect for post-mortem privacy to a growing recognition that personality rights do need protection post-mortem in a world where pop stars and actors are routinely re-created using AI. While the legislative motivation here may still be primarily to protect economic interests, we argue it also shows a concern for dignitary and privacy interests. Given the apparent concern for the appropriation of personality post-mortem, possibly in defiance or ignorance of what the deceased would have wished, we propose an early solution to regulate the rise of ghostbots, namely an enforceable ‘do not bot me’ clause in analogue or digital wills.

This article discusses the legal implications of a novel phenomenon, namely, digital reincarnations of deceased persons, sometimes known as post-mortem avatars, deepfakes, replicas, holographs, or chatbots. To elide these multiple names, we use the term 'ghostbots'. The piece is an early attempt to discuss the potential social and individual harms, roughly grouped around notions of privacy (including post-mortem privacy), property, personal data and reputation, arising from ghostbots, how they are regulated and whether they need to be adequately regulated further. For reasons of space and focus, the article does not deal with copyright implications, fraud, consumer protection, tort, product liability, and pornography laws, including the non-consensual use of intimate images (‘revenge porn’). This paper focuses on law, although we fully acknowledge and refer to the role of philosophy and ethics in this domain. We canvas two interesting legal developments with implications for ghostbots, namely, the proposed EU Artificial Intelligence (AI) Act and the 2021 New York law amending publicity rights to protect the rights of celebrities whose personality is used in post-mortem ‘replicas’. The latter especially evidences a remarkable shift from the norm we have chronicled in previous articles of no respect for post-mortem privacy to a growing recognition that personality rights do need protection post-mortem in a world where pop stars and actors are routinely re-created using AI. While the legislative motivation here may still be primarily to protect economic interests, we argue it also shows a concern for dignitary and privacy interests. Given the apparent concern for the appropriation of personality post-mortem, possibly in defiance or ignorance of what the deceased would have wished, we propose an early solution to regulate the rise of ghostbots, namely an enforceable ‘do not bot me’ clause in analogue or digital wills.

Given the recent detection of tetrodotoxin (TTX) in bivalve molluscs but the absence of a full collaborative validation study for TTX determination in a large number of shellfish samples, interlaboratory assessment of method performance was required to better understand current capabilities for accurate and reproducible TTX quantitation using chemical and immunoassay methods. OBJECTIVE: The aim was to conduct an interlaboratory study with multiple laboratories, using results to assess method performance and acceptability of different TTX testing methods. METHODS: Homogenous and stable mussel and oyster materials were assessed by participants using a range of published and in-house detection methods to determine mean TTX concentrations. Data were used to calculate recoveries, repeatability, and reproducibility, together with participant acceptability z-scores. RESULTS: Method performance characteristics were good, showing excellent sensitivity, recovery, and repeatability. Acceptable reproducibility was evidenced by HorRat values for all LC-MS/MS and ELISA methods being less than the 2.0 limit of acceptability. Method differences between the LC-MS/MS participants did not result in statistically different results. Method performance characteristics compared well with previously published single-laboratory validated methods and no statistical difference was found in results returned by ELISA in comparison with LC-MS/MS. CONCLUSION: The results from this study demonstrate that current LC-MS/MS methods and ELISA are on the whole capable of sensitive, accurate, and reproducible TTX quantitation in shellfish. Further work is recommended to expand the number of laboratories testing ELISA and to standardize an LC-MS/MS protocol to further improve interlaboratory precision. HIGHLIGHTS: Multiple mass spectrometric methods and a commercial ELISA have been successfully assessed through an interlaboratory study, demonstrating excellent performance.

Background Given the recent detection of tetrodotoxin (TTX) in bivalve molluscs but the absence of a full collaborative validation study for TTX determination in a large number of shellfish samples, interlaboratory assessment of method performance was required to better understand current capabilities for accurate and reproducible TTX quantitation using chemical and immunoassay methods. Objective The aim was to conduct an interlaboratory study with multiple laboratories, using results to assess method performance and acceptability of different TTX testing methods. Methods Homogenous and stable mussel and oyster materials were assessed by participants using a range of published and in-house detection methods to determine mean TTX concentrations. Data were used to calculate recoveries, repeatability, and reproducibility, together with participant acceptability z-scores. Results Method performance characteristics were good, showing excellent sensitivity, recovery, and repeatability. Acceptable reproducibility was evidenced by HorRat values for all LC–MS/MS and ELISA methods being less than the 2.0 limit of acceptability. Method differences between the LC–MS/MS participants did not result in statistically different results. Method performance characteristics compared well with previously published single-laboratory validated methods and no statistical difference was found in results returned by ELISA in comparison with LC–MS/MS. Conclusion The results from this study demonstrate that current LC–MS/MS methods and ELISA are on the whole capable of sensitive, accurate, and reproducible TTX quantitation in shellfish. Further work is recommended to expand the number of laboratories testing ELISA and to standardize an LC–MS/MS protocol to further improve interlaboratory precision. Highlights Multiple mass spectrometric methods and a commercial ELISA have been successfully assessed through an interlaboratory study, demonstrating excellent performance.

The European Commission asked EFSA to revise the Guidance on the risk assessment for birds and mammals. That guidance described how to perform risk assessment for birds and mammals from plant protection products, containing pesticide active substances, in accordance with Regulation (EU) 1107/2009. The current guidance document is an update of EFSA's existing guidance document titled ‘Risk assessment for Birds and Mammals’ which was published in 2009. It outlines a tiered risk assessment scheme covering dietary exposure, exposure via secondary poisoning and exposure via intake of contaminated water.

Large and densely sampled sensor datasets can contain a range of complex stochastic structures that are difficult to accommodate in conventional linear models. This can confound attempts to build a more complete picture of an animal's behavior by aggregating information across multiple asynchronous sensor platforms. The Livestock Informatics Toolkit (LIT) has been developed in R to better facilitate knowledge discovery of complex behavioral patterns across Precision Livestock Farming (PLF) data streams using novel unsupervised machine learning and information theoretic approaches. The utility of this analytical pipeline is demonstrated using data from a 6-month feed trial conducted on a closed herd of 185 mix-parity organic dairy cows. Insights into the tradeoffs between behaviors in time budgets acquired from ear tag accelerometer records were improved by augmenting conventional hierarchical clustering techniques with a novel simulation-based approach designed to mimic the complex error structures of sensor data. These simulations were then repurposed to compress the information in this data stream into robust empirically-determined encodings using a novel pruning algorithm. Nonparametric and semiparametric tests using mutual and pointwise information subsequently revealed complex nonlinear associations between encodings of overall time budgets and the order that cows entered the parlor to be milked.

The pathogenic significance of nucleotide variants commonly relies on nucleotide position within the gene, with exonic changes generally attributed to quantitative or qualitative alteration of protein biosynthesis, secretion, activity, or clearance. However, these changes may exert pleiotropic effects on both protein biology and mRNA splicing due to the overlapping of the amino acid and splicing codes, thus shaping the disease phenotypes. Here, we focused on hemophilia A, in which the definition of F8 variants’ causative role and association to bleeding phenotypes is crucial for proper classification, genetic counseling, and management of affected individuals. We extensively characterized a large panel of hemophilia A-causing variants (n = 30) within F8 exon 19 by combining and comparing in silico and recombinant expression analyses. We identified exonic variants with pleiotropic effects and dissected the altered protein features of all missense changes. Importantly, results from multiple prediction algorithms provided qualitative results, while recombinant assays allowed us to correctly infer the likely phenotype severity for 90% of variants. Molecular characterization of pathogenic variants was also instrumental for the development of tailored correction approaches to rescue splicing affecting variants or missense changes impairing protein folding. A single engineered U1snRNA rescued mRNA splicing of nine different variants and the use of a chaperone-like drug resulted in improved factor VIII protein secretion for four missense variants. Overall, dissection of the molecular mechanisms of a large panel of HA variants allowed precise classification of HA-affected individuals and favored the development of personalized therapeutic approaches.

From novels to films to tall tales told around the campfire, stories are as important as they are powerful. Well-told narratives have the ability to whisk us away to far away lands, showing us interesting people and ways of life that we may not have been able to ever imagine on our own. But the experience of being mentally transported by an engrossing narrative is more than just a vehicle for escapism and entertainment, it can bring about very real and important psychological changes.In Chapter 1, I begin by delving into Martha Nussbaum’s views on the importance of narrative, particularly novels, for the cultivation of what she calls the literary imagination, something she believes aids in the cultivation of ethical and political theories that allow us to thrive in democratic societies. In Chapter 2, I connect Nussbaum’s theoretical views with the empirical research on a phenomenon callednarrative transport and argue that it is the mechanism responsible for narrative impact theorized by Nussbaum. Chapter 3 lays out a series of three empirical studies meant to add to the literature in Chapter 2 and expand it to include the impact of narrative on specifically moral beliefs, attitudes, intentions, and behavior. Finally, Chapter 4 investigates the potential ethical issues surrounding the use of narrative transport to intentionally sway the mental states and behavior of others.

From novels to films to tall tales told around the campfire, stories are as important as they are powerful. Well-told narratives have the ability to whisk us away to far away lands, showing us interesting people and ways of life that we may not have been able to ever imagine on our own. But the experience of being mentally transported by an engrossing narrative is more than just a vehicle for escapism and entertainment, it can bring about very real and important psychological changes.In Chapter 1, I begin by delving into Martha Nussbaum’s views on the importance of narrative, particularly novels, for the cultivation of what she calls the literary imagination, something she believes aids in the cultivation of ethical and political theories that allow us to thrive in democratic societies. In Chapter 2, I connect Nussbaum’s theoretical views with the empirical research on a phenomenon callednarrative transport and argue that it is the mechanism responsible for narrative impact theorized by Nussbaum. Chapter 3 lays out a series of three empirical studies meant to add to the literature in Chapter 2 and expand it to include the impact of narrative on specifically moral beliefs, attitudes, intentions, and behavior. Finally, Chapter 4 investigates the potential ethical issues surrounding the use of narrative transport to intentionally sway the mental states and behavior of others.

Sensor technologies allow ethologists to continuously monitor the behaviors of large numbers of animals over extended periods of time. This creates new opportunities to study livestock behavior in commercial settings, but also new methodological challenges. Densely sampled behavioral data from large heterogeneous groups can contain a range of complex patterns and stochastic structures that may be difficult to visualize using conventional exploratory data analysis techniques. The goal of this research was to assess the efficacy of unsupervised machine learning tools in recovering complex behavioral patterns from such datasets to better inform subsequent statistical modeling. This methodological case study was carried out using records on milking order, or the sequence in which cows arrange themselves as they enter the milking parlor. Data was collected over a 6-month period from a closed group of 200 mixed-parity Holstein cattle on an organic dairy. Cows at the front and rear of the queue proved more consistent in their entry position than animals at the center of the queue, a systematic pattern of heterogeneity more clearly visualized using entropy estimates, a scale and distribution-free alternative to variance robust to outliers. Dimension reduction techniques were then used to visualize relationships between cows. No evidence of social cohesion was recovered, but Diffusion Map embeddings proved more adept than PCA at revealing the underlying linear geometry of this data. Median parlor entry positions from the pre- and post-pasture subperiods were highly correlated (R = 0.91), suggesting a surprising degree of temporal stationarity. Data Mechanics visualizations, however, revealed heterogeneous non-stationary among subgroups of animals in the center of the group and herd-level temporal outliers. A repeated measures model recovered inconsistent evidence of a relationships between entry position and cow attributes. Mutual conditional entropy tests, a permutation-bas

Introduction & Objectives: With the widespread use of robot-assistance for pelvic surgeries including prostatectomies, urologists are increasingly aware of intra- and postoperative complications unique to these procedures, including rises in intraocular pressure. While the Trendelenburg positioning required to achieve operative field exposure has been shown to increase intraoperative pressures in people without eye diseases, the literature lacks comprehensive assessments of intraocular pressure in patients with eye diseases. Method(s): A search was conducted on OvidSP Medline and PubMed for studies exploring the effects of patient positioning on intraocular pressure. Search terms used included 'intraocular pressure', 'prostatectomy', 'urologic surgery procedure', 'hysterectomy', 'gynaecology', 'head-down', 'patient positioning' and 'Trendelenburg'. Result(s): A total of three studies satisfied the inclusion criteria. All studies were prospective and observational in design and demonstrated a significant increase in intraocular pressure after placement in Trendelenburg position compared to baseline. Intraocular pressures at 60min after placement into Trendelenburg ranged from 17.0 to 25.1 mmHg. All of these increased with duration in Trendelenburg position, with intraocular pressures ranging between 19.1 to 28.3 mmHg after 180 minutes. All studies examined functional outcomes of Trendelenburg positioning by testing patients' visual fields. Two studies demonstrated no defects in visual field testing. One study found visual field defects in patients with and without eye diseases, with some persisting at 3 months' follow up. Conclusion(s): From the currently available studies, urologists should consider using the least steep Trendelenburg position required to attenuate elevations in intraocular pressure during robot-assisted radical prostatectomies for all patients. However, it appears that visual field defects are minimal and transient, thus routine full ophthalmologis

A solar sail propelled small satellite mission concept to intercept and potentially rendezvous with newly discovered transient interstellar objects (ISOs) is described. The mission concept derives from the proposal for a technology demonstration mission for exiting the solar system at high velocity, eventually to reach the focal region of the solar gravitational lens. The ISO mission concept is to fly a solar sail toward a holding orbit around the Sun and when the ISO orbit is confirmed, target the sailcraft to reach an escape velocity of over 6 AU/year. This would permit rapid response to a new ISO discovery and an intercept within 10 AU from the Sun. Two new proven interplanetary technologies are utilized to enable such a mission: i) interplanetary smallsats, such as those demonstrated by the MarCO mission, and ii) solar sails, such as demonstrated by LightSail and IKAROS missions and developed for NEA Scout and Solar Cruiser missions. Current technology work suggests that already within this decade such a mission could fly and reach an ISO moving through the solar system. It might enable the first encounter with an ISO to allow for imaging and spectroscopy, measurements of size and mass, potentially giving a unique information about the object’s origin and composition. A similar approach may be used to allow for a sample return.

Early detection and management of prostate cancer has evolved over the past decade, with a focus now on harm minimisation and reducing overdiagnosis and overtreatment, given the proven improvements in survival from randomised controlled trials. Multiparametric magnetic resonance imaging (mpMRI) is now an important aspect of the diagnostic pathway in prostate cancer, improving the detection of clinically significant prostate cancer, enabling accurate localisation of appropriate sites to biopsy, and reducing unnecessary biopsies in most patients with normal magnetic resonance imaging scans. Biopsies are now performed transperineally, substantially reducing the risk of post-procedure sepsis. Australian-led research has shown that prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has superior accuracy in the staging of prostate cancer than conventional imaging (CT and whole-body bone scan). Localised prostate cancer that is low risk (International Society for Urological Pathology [ISUP] grade 1, Gleason score 3 + 3 = 6; and ISUP grade group 2, Gleason score 3 + 4 = 7 with less than 10% pattern 4) can be offered active surveillance, reducing harms from overtreatment. Prostatectomy and definitive radiation remain the gold standard for localised intermediate and high risk disease. However, focal therapy is an emerging experimental treatment modality in Australia in carefully selected patients. The management of advanced prostate cancer treatment has evolved to now include several novel agents both in the metastatic hormone-sensitive and castration-resistant disease settings. Multimodal therapy with androgen deprivation therapy, additional systemic therapy and radiotherapy are often recommended. PSMA-based radioligand therapy has emerged as a treatment option for metastatic castration-resistant prostate cancer and is currently being evaluated in earlier disease states.

In the past, the digitization of archival collections has focused on capture of and access to plain images of textual material. In the current cultural heritage environment, particularly with the shift of many archives workers and patrons to telework during the COVID-19 pandemic, an image of the archival object alone is not enough. Today archival collections need to be searchable and transcribable. This session discusses the power of both technological developments and more traditional humanistic "people power" to enhance digitized archival collections at scale. Come and hear how archives are crowdsourcing transcriptions of digitized texts, both through "volunpeers" from the public and teleworking staff, and using informatics tools for new methods of seeing and understanding collections such as OCR and artificial intelligence (AI).

In the past, the digitization of archival collections has focused on capture of and access to plain images of textual material. In the current cultural heritage environment, particularly with the shift of many archives workers and patrons to telework during the COVID-19 pandemic, an image of the archival object alone is not enough. Today archival collections need to be searchable and transcribable. This session discusses the power of both technological developments and more traditional humanistic "people power" to enhance digitized archival collections at scale. Come and hear how archives are crowdsourcing transcriptions of digitized texts, both through "volunpeers" from the public and teleworking staff, and using informatics tools for new methods of seeing and understanding collections such as OCR and artificial intelligence (AI).

We present initial results of an ongoing engineering study on the feasibility of a space mission to the focal region of the solar gravitational lens (SGL). The mission goal is to conduct exoplanet imaging operations at heliocentric distances in the range ~548-900 astronomical units (AU). Starting at 548 AU from the Sun, light from an exoplanet located behind the Sun is greatly amplified by the SGL. The objective is to capture this light and use it for multipixel imaging of an exoplanet up to 100 light years distant. Using a meter-class telescope one can produce images of the exoplanet with a surface resolution measured in tens of kilometers and to identify signs of habitability. The data are acquired pixel-by-pixel while moving an imaging spacecraft within the image. Given the long duration of the mission, decades to 900 AU, we address an architecture for the fastest possible transit time while reducing mission risk and overall cost. The mission architecture implements solar sailing technologies and in-space aggregation of modularized functional units to form mission capable spacecraft. The study reveals elements of such a challenging mission, but it is nevertheless found to be feasible with technologies that are either extant or in active development., Comment: 43 pages, 8 figures, and 9 tables

The solar gravitational lens (SGL) provides a factor of $10^{11}$ amplification for viewing distant point sources beyond our solar system. As such, it may be used for resolved imaging of extended sources, such as exoplanets, not possible otherwise. To use the SGL, a spacecraft carrying a modest telescope and a coronagraph must reach the SGLs focal region, that begins at $\sim$550 astronomical units (AU) from the Sun and is oriented outward along the line connecting the distant object and the Sun. No spacecraft has ever reached even a half of that distance; and to do so within a reasonable mission lifetime (e.g., less than 25 years) and affordable cost requires a new type of mission design, using solar sails and microsats ($<100$~kg). The payoff is high -- using the SGL is the only practical way we can ever get a high-resolution, multi-pixel image of an Earth-like exoplanet, one that we identify as potentially habitable. This paper describes a novel mission design starting with a rideshare launch from the Earth, spiraling in toward the Sun, and then flying around it to achieve solar system exit speeds of over $20$ AU/year. A new sailcraft design is used to make possible high area to mass ratio for the sailcraft. The mission design enables other fast solar system missions, starting with a proposed very low cost technology demonstration mission (TDM) to prove the functionality and operation of the microsat-solar sail design and then, building on the TDM, missions to explore distant regions of the solar system, and those to study Kuiper Belt objects (KBOs) and the recently discovered interstellar objects (ISOs) are also possible., Comment: 18 pages, 10 figures

A solar sail propelled small satellite mission concept to intercept and potentially rendezvous with newly discovered transient interstellar objects (ISOs) is described. The mission concept derives from the proposal for a technology demonstration mission for exiting the solar system at high velocity, eventually to reach the focal region of the solar gravitational lens. The ISO mission concept is to fly a solar sail toward a holding orbit around the Sun and when the ISO orbit is confirmed, target the sailcraft to reach an escape velocity of over 6 AU/year. This would permit rapid response to a new ISO discovery and an intercept within 10 AU from the Sun. Two new proven interplanetary technologies are utilized to enable such a mission: i) interplanetary smallsats, such as those demonstrated by the MarCO mission, and ii) solar sails, such as demonstrated by LightSail and IKAROS missions and developed for NEA Scout and Solar Cruiser missions. Current technology work suggests that already within this decade such a mission could fly and reach an ISO moving through the solar system. It might enable the first encounter with an ISO to allow for imaging and spectroscopy, measurements of size and mass, potentially giving a unique information about the object's origin and composition. A similar approach may be used to allow for a sample return., Comment: 17 pages, 9 figures

The solar gravitational lens (SGL) provides a factor of $10^{11}$ amplification for viewing distant point sources beyond our solar system. As such, it may be used for resolved imaging of extended sources, such as exoplanets, not possible otherwise. To use the SGL, a spacecraft carrying a modest telescope and a coronagraph must reach the SGLs focal region, that begins at $\sim$550 astronomical units (AU) from the Sun and is oriented outward along the line connecting the distant object and the Sun. No spacecraft has ever reached even a half of that distance; and to do so within a reasonable mission lifetime (e.g., less than 25 years) and affordable cost requires a new type of mission design, using solar sails and microsats ($<100$~kg). The payoff is high -- using the SGL is the only practical way we can ever get a high-resolution, multi-pixel image of an Earth-like exoplanet, one that we identify as potentially habitable. This paper describes a novel mission design starting with a rideshare launch from the Earth, spiraling in toward the Sun, and then flying around it to achieve solar system exit speeds of over $20$ AU/year. A new sailcraft design is used to make possible high area to mass ratio for the sailcraft. The mission design enables other fast solar system missions, starting with a proposed very low cost technology demonstration mission (TDM) to prove the functionality and operation of the microsat-solar sail design and then, building on the TDM, missions to explore distant regions of the solar system, and those to study Kuiper Belt objects (KBOs) and the recently discovered interstellar objects (ISOs) are also possible., Comment: 18 pages, 10 figures

A solar sail propelled small satellite mission concept to intercept and potentially rendezvous with newly discovered transient interstellar objects (ISOs) is described. The mission concept derives from the proposal for a technology demonstration mission for exiting the solar system at high velocity, eventually to reach the focal region of the solar gravitational lens. The ISO mission concept is to fly a solar sail toward a holding orbit around the Sun and when the ISO orbit is confirmed, target the sailcraft to reach an escape velocity of over 6 AU/year. This would permit rapid response to a new ISO discovery and an intercept within 10 AU from the Sun. Two new proven interplanetary technologies are utilized to enable such a mission: i) interplanetary smallsats, such as those demonstrated by the MarCO mission, and ii) solar sails, such as demonstrated by LightSail and IKAROS missions and developed for NEA Scout and Solar Cruiser missions. Current technology work suggests that already within this decade such a mission could fly and reach an ISO moving through the solar system. It might enable the first encounter with an ISO to allow for imaging and spectroscopy, measurements of size and mass, potentially giving a unique information about the object's origin and composition. A similar approach may be used to allow for a sample return., Comment: 17 pages, 9 figures

Currently, there is a growing interest in developing biopesticides and increasing their share in the plant protection market as sustainable tools in integrated pest management (IPM). Therefore, it is important that regulatory requirements are consistent and thorough in consideration of biopesticides’ unique properties. While microbial pesticides generally have a lower risk profile, they present special challenges in non-target organism testing and risk assessment since, in contrast to chemical pesticides, their modes of action include infectivity and pathogenicity rather than toxicity alone. For this reason, non-target organism testing guidelines designed for conventional chemical pesticides are not necessarily directly applicable to microbial pesticides. Many stakeholders have recognised the need for improvements in the guidance available for testing microbial pesticides with honey bees, particularly given the increasing interest in development and registration of microbial pesticides and concerns over risks to pollinators. This paper provides an overview of the challenges with testing and assessment of the effects of microbial pesticides on honey bees (Apis mellifera), which have served as a surrogate for both Apis and non-Apis bees, and provides a foundation toward developing improved testing methods.

We examined the solar gravitational lens (SGL) as the means to produce direct high-resolution, multipixel images of exoplanets. The properties of the SGL are remarkable: it offers maximum light amplification of ~1e11 and angular resolution of ~1e-10 arcsec. A probe with a 1-m telescope in the SGL focal region can image an exoplanet at 30 pc with 10-kilometer resolution on its surface, sufficient to observe seasonal changes, oceans, continents, surface topography. We reached and exceeded all objectives set for our study: We developed a new wave-optical approach to study the imaging of exoplanets while treating them as extended, resolved, faint sources at large but finite distances. We properly accounted for the solar corona brightness. We developed deconvolution algorithms and demonstrated the feasibility of high-quality image reconstruction under realistic conditions. We have proven that multipixel imaging and spectroscopy of exoplanets with the SGL are feasible. We have developed a new mission concept that delivers an array of optical telescopes to the SGL focal region relying on three innovations: i) a new way to enable direct exoplanet imaging, ii) use of smallsats solar sails fast transit through the solar system and beyond, iii) an open architecture to take advantage of swarm technology. This approach enables entirely new missions, providing a great leap in capabilities for NASA and the greater aerospace community. Our results are encouraging as they lead to a realistic design for a mission that will be able to make direct resolved images of exoplanets in our stellar neighborhood. It could allow exploration of exoplanets relying on the SGL capabilities decades, if not centuries, earlier than possible with other extant technologies. The architecture and mission concepts for a mission to the strong interference region of the SGL are promising and should be explored further., Comment: Final Report for the NASA's Innovative Advanced Concepts (NIAC) Phase II proposal. 91 pages, 50 figures, 5 tables

DDD: Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. While Milan Criteria (MC) generalized the practice of LT for HCC and improved outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the hazard associated with liver transplantation in HCC (HALTHCC) in an international cohort. From 2002-2014, 4,089 patients (both MC in and out [25.2%]) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre-LT levels of alpha feto-protein, model for end stage liver disease sodium score, and tumor burden score was recalibrated amongst a randomly selected cohort (n=1,021) and validated in the remainder (n=3,068). This study demonstrated significant heterogeneity by site and year, reflecting practice trends over the last decade. On explant pathology, both vascular invasion(VI) and poorly differentiated component(PDC) increased with increasing HALTHCC score. The lowest risk patients (HALTHCC 0-5) had lower rates of VI and PDC than the highest risk patients (HALTHCC>35) (VI:7.7%[1.2-14.2] vs 70.6%[48.3-92.9] and PDC:4.6%[0.1-9.8%] vs 47.1%[22.6-71.5]; P<0.0001 for both). This trend was robust to MC status. This international study was used to adjust the coefficients in the HALTHCC score. Before recalibration, HALTHCC had the greatest discriminatory ability for overall survival (C-index=0.61) compared to all previously reported scores. Following recalibration, the prognostic utility increased for both recurrence (C-index=0.71) and overall survival (C-index=0.63). CONCLUSION: This large international trial validated and refined the role for the continuous risk metric, HALTHCC, in establishing pre-LT risk amongst candidates with HCC worldwide. Prospective trials introducing HALTHCC into clinical practice are warran

Background: General practitioners (GPS) and general practice nurses (GPNs) face increasing demands to provide palliative care (PC) or end-of-life care (EoLC) as the population ages. To enhance primary EoLC, the facilitators and barriers to their provision need to be understood. Objective: To provide a comprehensive description of the facilitators and barriers to GP and GPN provision of PC or EoLC. Method: Systematic literature review. Data included papers (2000 to 2017) sought from Medline, PsycInfo, Embase, Joanna Briggs Institute and Cochrane databases. Results: From 6209 journal articles, 62 reviewed papers reported the GP's and GPN's role in EoLC or PC practice. Six themes emerged: Patient factors; personal GP factors; general practice factors; relational factors; co-ordination of care; availability of services. Four specific settings were identified: Aged care facilities, out-of-hours care and resource-constrained settings (rural, and low-income and middle-income countries). Most GPS provide EoLC to some extent, with greater professional experience leading to increased comfort in performing this form of care. The organisation of primary care at practice, local and national level impose numerous structural barriers that impede more significant involvement. There are potential gaps in service provision where GPNs may provide significant input, but there is a paucity of studies describing GPN routine involvement in EoLC. Conclusions: While primary care practitioners have a natural role to play in EoLC, significant barriers exist to improved GP and GPN involvement in PC. More work is required on the role of GPNs.

BACKGROUND: General practitioners (GPs) and general practice nurses (GPNs) face increasing demands to provide palliative care (PC) or end-of-life care (EoLC) as the population ages. In order to maximise the impact of GPs and GPNs, the impact of different models of care that have been developed to support their practice of EoLC needs to be understood.OBJECTIVE: To examine published models of EoLC that incorporate or support GP and GPN practice, and their impact on patients, families and the health system.METHOD: Systematic literature review. Data included papers (2000 to 2017) sought from Medline, Psychinfo, Embase, Joanna Briggs Institute and Cochrane databases.RESULTS: From 6209 journal articles, 13 papers reported models of care supporting the GP and GPN's role in EoLC or PC practice. Services and guidelines for clinical issues have mixed impact on improving symptoms, but improved adherence to clinical guidelines. National Frameworks facilitated patients being able to die in their preferred place. A single specialist PC-GP case conference reduced hospitalisations, better maintained functional capacity and improved quality of life parameters in both patients with cancer and without cancer. No studies examined models of care aimed at supporting GPNs.CONCLUSIONS: Primary care practitioners have a natural role to play in EoLC, and most patient and health system outcomes are substantially improved with their involvement. Successful integrative models need to be tested, particularly in non-malignant diseases. Such models need to be explored further. More work is required on the role of GPNs and how to support them in this role.

Endometrial cancer is the sixth most common cancer in women, with a rising incidence worldwide. Current approaches for the diagnosis and screening of endometrial cancer are invasive, expensive or of moderate diagnostic accuracy, limiting their clinical utility. There is a need for cost-effective and minimally invasive approaches to facilitate the early detection and timely management of endometrial cancer. We analysed blood plasma samples in a cross-sectional diagnostic accuracy study of women with endometrial cancer (n = 342), its precursor lesion atypical hyperplasia (n = 68) and healthy controls (n = 242, total n = 652) using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and machine learning algorithms. We show that blood-based infrared spectroscopy has the potential to detect endometrial cancer with 87% sensitivity and 78% specificity. Its accuracy is highest for Type I endometrial cancer, the most common subtype, and for atypical hyperplasia, with sensitivities of 91% and 100%, and specificities of 81% and 88%, respectively. Our large-cohort study shows that a simple blood test could enable the early detection of endometrial cancer of all stages in symptomatic women and provide the basis of a screening tool in high-risk groups. Such a test has the potential not only to differentially diagnose endometrial cancer but also to detect its precursor lesion atypical hyperplasia—the early recognition of which may allow fertility sparing management and cancer prevention.

Endometrial cancer is the sixth most common cancer in women, with a rising incidence worldwide. Current approaches for the diagnosis and screening of endometrial cancer are invasive, expensive or of moderate diagnostic accuracy, limiting their clinical utility. There is a need for cost-effective and minimally invasive approaches to facilitate the early detection and timely management of endometrial cancer. We analysed blood plasma samples in a cross-sectional diagnostic accuracy study of women with endometrial cancer (n = 342), its precursor lesion atypical hyperplasia (n = 68) and healthy controls (n = 242, total n = 652) using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and machine learning algorithms. We show that blood-based infrared spectroscopy has the potential to detect endometrial cancer with 87% sensitivity and 78% specificity. Its accuracy is highest for Type I endometrial cancer, the most common subtype, and for atypical hyperplasia, with sensitivities of 91% and 100%, and specificities of 81% and 88%, respectively. Our large-cohort study shows that a simple blood test could enable the early detection of endometrial cancer of all stages in symptomatic women and provide the basis of a screening tool in high-risk groups. Such a test has the potential not only to differentially diagnose endometrial cancer but also to detect its precursor lesion atypical hyperplasia—the early recognition of which may allow fertility sparing management and cancer prevention.

Endometrial cancer is the sixth most common cancer in women, with a rising incidence worldwide. Current approaches for the diagnosis and screening of endometrial cancer are invasive, expensive or of moderate diagnostic accuracy, limiting their clinical utility. There is a need for cost-effective and minimally invasive approaches to facilitate the early detection and timely management of endometrial cancer. We analysed blood plasma samples in a cross-sectional diagnostic accuracy study of women with endometrial cancer (n = 342), its precursor lesion atypical hyperplasia (n = 68) and healthy controls (n = 242, total n = 652) using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and machine learning algorithms. We show that blood-based infrared spectroscopy has the potential to detect endometrial cancer with 87% sensitivity and 78% specificity. Its accuracy is highest for Type I endometrial cancer, the most common subtype, and for atypical hyperplasia, with sensitivities of 91% and 100%, and specificities of 81% and 88%, respectively. Our large-cohort study shows that a simple blood test could enable the early detection of endometrial cancer of all stages in symptomatic women and provide the basis of a screening tool in high-risk groups. Such a test has the potential not only to differentially diagnose endometrial cancer but also to detect its precursor lesion atypical hyperplasia—the early recognition of which may allow fertility sparing management and cancer prevention.

Bone health is extremely important in early childhood because children with low bone mineral density (BMD) are at a greater risk of bone fractures. While physical activity and intake of both calcium and vitamin D benefit BMD in older children, there is limited research on the determinants of good bone health in early childhood. The aim of this cross-sectional study was to investigate the impact of diet, physical activity, and body composition on BMD at five years of age. Dietary intakes and physical activity levels were measured through questionnaires. Whole body BMD was measured by dual-energy X-ray absorptiometry in 102 children. Child weight, height, circumferences, skinfolds and serum 25-hydroxyvitamin D (25OHD) concentrations were assessed. There was no association between BMD and dietary calcium, dietary vitamin D, 25OHD, physical activity, or sedentary behaviour. Several measures of body composition were significantly positively associated with BMD; however, neither fat mass nor lean body mass was associated with BMD.Conclusion: Although we found no association between self-reported dietary and lifestyle factors and bone health in early years, increased body size was linked with higher BMD. These findings are important as identifying modifiable factors that can improve bone health at a young age is of utmost importance.What is Known:• Bone health is extremely important in early childhood, as children with low bone mineral density (BMD) are at greater risk of bone fractures.• Physical activity has been found to be beneficial for bone health in adolescents, and body composition has also been associated with BMD in teenage years.• Limited research on the determinants of good bone health in early childhood.What is New:• No association between self-reported lifestyle and dietary factors with bone health in early childhood.• Increased body size was associated with higher BMD at five years of age.

We examined the solar gravitational lens (SGL) as the means to produce direct high-resolution, multipixel images of exoplanets. The properties of the SGL are remarkable: it offers maximum light amplification of ~1e11 and angular resolution of ~1e-10 arcsec. A probe with a 1-m telescope in the SGL focal region can image an exoplanet at 30 pc with 10-kilometer resolution on its surface, sufficient to observe seasonal changes, oceans, continents, surface topography. We reached and exceeded all objectives set for our study: We developed a new wave-optical approach to study the imaging of exoplanets while treating them as extended, resolved, faint sources at large but finite distances. We properly accounted for the solar corona brightness. We developed deconvolution algorithms and demonstrated the feasibility of high-quality image reconstruction under realistic conditions. We have proven that multipixel imaging and spectroscopy of exoplanets with the SGL are feasible. We have developed a new mission concept that delivers an array of optical telescopes to the SGL focal region relying on three innovations: i) a new way to enable direct exoplanet imaging, ii) use of smallsats solar sails fast transit through the solar system and beyond, iii) an open architecture to take advantage of swarm technology. This approach enables entirely new missions, providing a great leap in capabilities for NASA and the greater aerospace community. Our results are encouraging as they lead to a realistic design for a mission that will be able to make direct resolved images of exoplanets in our stellar neighborhood. It could allow exploration of exoplanets relying on the SGL capabilities decades, if not centuries, earlier than possible with other extant technologies. The architecture and mission concepts for a mission to the strong interference region of the SGL are promising and should be explored further.

ObjectivesTo approximate the rate of familial myasthenia gravis and the coexistence of other autoimmune disorders in the patients and their families.DesignRetrospective cohort study.SettingClinics across North America.ParticipantsThe study included 1032 patients diagnosed with acetylcholine receptor antibody (AChR)-positive myasthenia gravis.MethodsPhenotype information of 1032 patients diagnosed with AChR-positive myasthenia gravis was obtained from clinics at 14 centres across North America between January 2010 and January 2011. A critical review of the epidemiological literature on the familial rate of myasthenia gravis was also performed.ResultsAmong 1032 patients, 58 (5.6%) reported a family history of myasthenia gravis. A history of autoimmune diseases was present in 26.6% of patients and in 28.4% of their family members.DiscussionThe familial rate of myasthenia gravis was higher than would be expected for a sporadic disease. Furthermore, a high proportion of patients had a personal or family history of autoimmune disease. Taken together, these findings suggest a genetic contribution to the pathogenesis of myasthenia gravis.

Endometrial cancer is the sixth most common cancer in women, with a rising incidence worldwide. Current approaches for the diagnosis and screening of endometrial cancer are invasive, expensive or of moderate diagnostic accuracy, limiting their clinical utility. There is a need for cost-effective and minimally invasive approaches to facilitate the early detection and timely management of endometrial cancer. We analysed blood plasma samples in a cross-sectional diagnostic accuracy study of women with endometrial cancer (n = 342), its precursor lesion atypical hyperplasia (n = 68) and healthy controls (n = 242, total n = 652) using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and machine learning algorithms. We show that blood-based infrared spectroscopy has the potential to detect endometrial cancer with 87% sensitivity and 78% specificity. Its accuracy is highest for Type I endometrial cancer, the most common subtype, and for atypical hyperplasia, with sensitivities of 91% and 100%, and specificities of 81% and 88%, respectively. Our large-cohort study shows that a simple blood test could enable the early detection of endometrial cancer of all stages in symptomatic women and provide the basis of a screening tool in high-risk groups. Such a test has the potential not only to differentially diagnose endometrial cancer but also to detect its precursor lesion atypical hyperplasia—the early recognition of which may allow fertility sparing management and cancer prevention.

Endometrial cancer is the sixth most common cancer in women, with a rising incidence worldwide. Current approaches for the diagnosis and screening of endometrial cancer are invasive, expensive or of moderate diagnostic accuracy, limiting their clinical utility. There is a need for cost-effective and minimally invasive approaches to facilitate the early detection and timely management of endometrial cancer. We analysed blood plasma samples in a cross-sectional diagnostic accuracy study of women with endometrial cancer (n = 342), its precursor lesion atypical hyperplasia (n = 68) and healthy controls (n = 242, total n = 652) using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and machine learning algorithms. We show that blood-based infrared spectroscopy has the potential to detect endometrial cancer with 87% sensitivity and 78% specificity. Its accuracy is highest for Type I endometrial cancer, the most common subtype, and for atypical hyperplasia, with sensitivities of 91% and 100%, and specificities of 81% and 88%, respectively. Our large-cohort study shows that a simple blood test could enable the early detection of endometrial cancer of all stages in symptomatic women and provide the basis of a screening tool in high-risk groups. Such a test has the potential not only to differentially diagnose endometrial cancer but also to detect its precursor lesion atypical hyperplasia—the early recognition of which may allow fertility sparing management and cancer prevention.

We examined the solar gravitational lens (SGL) as the means to produce direct high-resolution, multipixel images of exoplanets. The properties of the SGL are remarkable: it offers maximum light amplification of ~1e11 and angular resolution of ~1e-10 arcsec. A probe with a 1-m telescope in the SGL focal region can image an exoplanet at 30 pc with 10-kilometer resolution on its surface, sufficient to observe seasonal changes, oceans, continents, surface topography. We reached and exceeded all objectives set for our study: We developed a new wave-optical approach to study the imaging of exoplanets while treating them as extended, resolved, faint sources at large but finite distances. We properly accounted for the solar corona brightness. We developed deconvolution algorithms and demonstrated the feasibility of high-quality image reconstruction under realistic conditions. We have proven that multipixel imaging and spectroscopy of exoplanets with the SGL are feasible. We have developed a new mission concept that delivers an array of optical telescopes to the SGL focal region relying on three innovations: i) a new way to enable direct exoplanet imaging, ii) use of smallsats solar sails fast transit through the solar system and beyond, iii) an open architecture to take advantage of swarm technology. This approach enables entirely new missions, providing a great leap in capabilities for NASA and the greater aerospace community. Our results are encouraging as they lead to a realistic design for a mission that will be able to make direct resolved images of exoplanets in our stellar neighborhood. It could allow exploration of exoplanets relying on the SGL capabilities decades, if not centuries, earlier than possible with other extant technologies. The architecture and mission concepts for a mission to the strong interference region of the SGL are promising and should be explored further., Comment: Final Report for the NASA's Innovative Advanced Concepts (NIAC) Phase II proposal. 91 pages, 50 figures, 5 tables

Endometrial cancer is the sixth most common cancer in women, with a rising incidence worldwide. Current approaches for the diagnosis and screening of endometrial cancer are invasive, expensive or of moderate diagnostic accuracy, limiting their clinical utility. There is a need for cost-effective and minimally invasive approaches to facilitate the early detection and timely management of endometrial cancer. We analysed blood plasma samples in a cross-sectional diagnostic accuracy study of women with endometrial cancer (n = 342), its precursor lesion atypical hyperplasia (n = 68) and healthy controls (n = 242, total n = 652) using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and machine learning algorithms. We show that blood-based infrared spectroscopy has the potential to detect endometrial cancer with 87% sensitivity and 78% specificity. Its accuracy is highest for Type I endometrial cancer, the most common subtype, and for atypical hyperplasia, with sensitivities of 91% and 100%, and specificities of 81% and 88%, respectively. Our large-cohort study shows that a simple blood test could enable the early detection of endometrial cancer of all stages in symptomatic women and provide the basis of a screening tool in high-risk groups. Such a test has the potential not only to differentially diagnose endometrial cancer but also to detect its precursor lesion atypical hyperplasia—the early recognition of which may allow fertility sparing management and cancer prevention.

Adapting dashboard design to different contexts of use is an open question in visualisation research. Dashboard designers often seek to strike a balance between dashboard adaptability and ease-of-use, and in hospitals challenges arise from the vast diversity of key metrics, data models and users involved at different organizational levels. In this design study, we present QualDash, a dashboard generation engine that allows for the dynamic configuration and deployment of visualisation dashboards for healthcare quality improvement (QI). We present a rigorous task analysis based on interviews with healthcare professionals, a co-design workshop and a series of one-on-one meetings with front line analysts. From these activities we define a metric card metaphor as a unit of visual analysis in healthcare QI, using this concept as a building block for generating highly adaptable dashboards, and leading to the design of a Metric Specification Structure (MSS). Each MSS is a JSON structure which enables dashboard authors to concisely configure unit-specific variants of a metric card, while offloading common patterns that are shared across cards to be preset by the engine. We reflect on deploying and iterating the design of QualDash in cardiology wards and pediatric intensive care units of five NHS hospitals. Finally, we report evaluation results that demonstrate the adaptability, ease-of-use and usefulness of QualDash in a real-world scenario.

Objectives To approximate the rate of familial myasthenia gravis and the coexistence of other autoimmune disorders in the patients and their families. Design Retrospective cohort study. Setting Clinics across North America. Participants The study included 1032 patients diagnosed with acetylcholine receptor antibody (AChR)-positive myasthenia gravis. Methods Phenotype information of 1032 patients diagnosed with AChR-positive myasthenia gravis was obtained from clinics at 14 centres across North America between January 2010 and January 2011. A critical review of the epidemiological literature on the familial rate of myasthenia gravis was also performed. Results Among 1032 patients, 58 (5.6%) reported a family history of myasthenia gravis. A history of autoimmune diseases was present in 26.6% of patients and in 28.4% of their family members. Discussion The familial rate of myasthenia gravis was higher than would be expected for a sporadic disease. Furthermore, a high proportion of patients had a personal or family history of autoimmune disease. Taken together, these findings suggest a genetic contribution to the pathogenesis of myasthenia gravis.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. Background: General practitioners (GPs) and general practice nurses (GPNs) face increasing demands to provide palliative care (PC) or end-of-life care (EoLC) as the population ages. In order to maximise the impact of GPs and GPNs, the impact of different models of care that have been developed to support their practice of EoLC needs to be understood. Objective: To examine published models of EoLC that incorporate or support GP and GPN practice, and their impact on patients, families and the health system. Method: Systematic literature review. Data included papers (2000 to 2017) sought from Medline, Psychinfo, Embase, Joanna Briggs Institute and Cochrane databases. Results: From 6209 journal articles, 13 papers reported models of care supporting the GP and GPN's role in EoLC or PC practice. Services and guidelines for clinical issues have mixed impact on improving symptoms, but improved adherence to clinical guidelines. National Frameworks facilitated patients being able to die in their preferred place. A single specialist PC-GP case conference reduced hospitalisations, better maintained functional capacity and improved quality of life parameters in both patients with cancer and without cancer. No studies examined models of care aimed at supporting GPNs. Conclusions: Primary care practitioners have a natural role to play in EoLC, and most patient and health system outcomes are substantially improved with their involvement. Successful integrative models need to be tested, particularly in non-malignant diseases. Such models need to be explored further. More work is required on the role of GPNs and how to support them in this role.