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Bayesian inference is a powerful tool in gravitational-wave astronomy. It enables us to deduce the properties of merging compact-object binaries and to determine how these mergers are distributed as a population according to mass, spin, and redshift. As key results are increasingly derived using Bayesian inference, there is increasing scrutiny on Bayesian methods. In this review, we discuss the phenomenon of model misspecification, in which results obtained with Bayesian inference are misleading because of deficiencies in the assumed model(s). Such deficiencies can impede our inferences of the true parameters describing physical systems. They can also reduce our ability to distinguish the ‘best fitting’ model: it can be misleading to say that Model A is preferred over Model B if both models are manifestly poor descriptions of reality. Broadly speaking, there are two ways in which models fail. Firstly, models that fail to adequately describe the data (either the signal or the noise) have misspecified likelihoods. Secondly, population models—designed, for example, to describe the distribution of black hole masses—may fail to adequately describe the true population due to a misspecified prior. We recommend tests and checks that are useful for spotting misspecified models using examples inspired by gravitational-wave astronomy. We include companion python notebooks to illustrate essential concepts.
Background: Electronic hand hygiene monitoring systems (EHHMSs) are being increasingly utilized to improve hand hygiene outcomes. Following the implementation of an EHHMS at a large, academic medical center, an interdisciplinary team developed a web-based survey to gather information on employee’s perceptions and behaviors surrounding the EHHMS. Methods: In total, 1,273 complete responses were collected. Responses were analyzed using Stata version 16 statistical software with 2-tailed tests and .05 significance level. Multivariate logistic regression models were constructed to examine factors associated with negative perceptions of the EHHMS and of wearing the EHHMS radiofrequency identification (RFID) badge. Supporting qualitative analysis was performed using Atlas.ti version 9 software. Results: The general sentiment toward the monitoring system was neutral (38%) to negative (37%). The same was true for respondents’ sentiments toward wearing the RFID badge. Of respondents who interact with the system, 48% feel that the system does not capture hand hygiene data accurately. The EHHMS had limited influence on employee’s hand hygiene habits: 27% significant influence and 54% little-to-no influence. Respondents of younger age, those employed as a registered nurse, scientist, physician, or master’s level clinician, and those working at the satellite hospital were significantly more likely to have negative perceptions of the EHHMS. Negative perceptions were also significantly more likely among respondents familiar with the institution’s hand hygiene policy and those who had a negative opinion of seeing the hand hygiene data of others. Negative perceptions of the EHHMS RFID badge were significantly more likely among respondents of younger age, those employed as a registered nurse, scientist, physician, or master’s level clinician, those working at the satellite hospital, and those with a negative perception of seeing the hand hygiene data of others. Employment in a role providing direct patient care and those employed at the institution for >1 year were also significantly more likely to have a negative perception. Conclusions: Negative and neutral opinions dominate perceptions of the EHHMS considered in this analysis. Respondents expressed concerns with accuracy of the EHHMS data collection. The system’s limited influence is likely a result of limited familiarity, limited performance feedback, and employee frustration and concerns. These findings provide opportunities for improvement in future implementation of EHHMS. Based on these results, implementation of EHHMS would be best be supported by coordinated backing from administration and leadership, advanced planning and education, and frequent, effective communication. Additional research and evaluation are required to optimize implementation of electronic hand hygiene monitoring systems, with the goal of improving hand hygiene outcomes.
This study aimed to explore the association between hyperglycemia in pregnancy (type 2 diabetes (T2D) and gestational diabetes mellitus (GDM)) and child developmental risk in Europid and Aboriginal women.
PANDORA is a longitudinal birth cohort recruited from a hyperglycemia in pregnancy register, and from normoglycemic women in antenatal clinics. The Wave 1 substudy included 308 children who completed developmental and behavioral screening between age 18 and 60 months. Developmental risk was assessed using the Ages and Stages Questionnaire (ASQ) or equivalent modified ASQ for use with Aboriginal children. Emotional and behavioral risk was assessed using the Strengths and Difficulties Questionnaire. Multivariable logistic regression was used to assess the association between developmental scores and explanatory variables, including maternal T2D in pregnancy or GDM.
After adjustment for ethnicity, maternal and child variables, and socioeconomic measures, maternal hyperglycemia was associated with increased developmental “concern” (defined as score ≥1 SD below mean) in the fine motor (T2D odds ratio (OR) 5.30, 95% CI 1.77–15.80; GDM OR 3.96, 95% CI 1.55–10.11) and problem-solving (T2D OR 2.71, 95% CI 1.05–6.98; GDM OR 2.54, 95% CI 1.17–5.54) domains, as well as increased “risk” (score ≥2 SD below mean) in at least one domain (T2D OR 5.33, 95% CI 1.85–15.39; GDM OR 4.86, 95% CI 1.95–12.10). Higher maternal education was associated with reduced concern in the problem-solving domain (OR 0.27, 95% CI 0.11–0.69) after adjustment for maternal hyperglycemia.
Maternal hyperglycemia is associated with increased developmental concern and may be a potential target for intervention so as to optimize developmental trajectories.
Findings from brain imaging studies with small samples can show limited reproducibility. Thus, we tested whether the evidence that a transdiagnostic eating disorder treatment reduces responsivity of brain valuation regions to thin models and high-calorie binge foods, the intervention targets, from a smaller earlier trial emerged when we recruited additional participants.
Women with DSM-5 eating disorders (N = 138) were randomized to the dissonance-based body project treatment (BPT) or a waitlist control condition and completed functional magnetic resonance imaging (fMRI) scans assessing neural response to thin models and high-calorie foods at pretest and posttest.
BPT v. control participants showed significantly greater reductions in responsivity of regions implicated in reward valuation (caudate) and attentional motivation (precuneus) to thin v. average-weight models, echoing findings from the smaller sample. Data from this larger sample also provided novel evidence that BPT v. control participants showed greater reductions in responsivity of regions implicated in reward valuation (ventrolateral prefrontal cortex) and food craving (hippocampus) to high-calorie binge foods v. low-calorie foods, as well as significantly greater reductions in eating disorder symptoms, abstinence from binge eating and purging behaviors, palatability ratings for high calorie foods, monetary value for high-calorie binge foods, and significantly greater increases in attractiveness ratings of average weight models.
Results from this larger sample provide evidence that BPT reduces valuation of the thin ideal and high-calorie binge foods, the intervention targets, per objective brain imaging data, and produces clinically meaningful reductions in eating pathology.
Recommendations for promoting mental health during the COVID-19 pandemic include maintaining social contact, through virtual rather than physical contact, moderating substance/alcohol use, and limiting news and media exposure. We seek to understand if these pandemic-related behaviors impact subsequent mental health.
Daily online survey data were collected on adults during May/June 2020. Measures were of daily physical and virtual (online) contact with others; substance and media use; and indices of psychological striving, struggling and COVID-related worry. Using random-intercept cross-lagged panel analysis, dynamic within-person cross-lagged effects were separated from more static individual differences.
In total, 1148 participants completed daily surveys [657 (57.2%) females, 484 (42.1%) males; mean age 40.6 (s.d. 12.4) years]. Daily increases in news consumed increased COVID-related worrying the next day [cross-lagged estimate = 0.034 (95% CI 0.018–0.049), FDR-adjusted p = 0.00005] and vice versa [0.03 (0.012–0.048), FDR-adjusted p = 0.0017]. Increased media consumption also exacerbated subsequent psychological struggling [0.064 (0.03–0.098), FDR-adjusted p = 0.0005]. There were no significant cross-lagged effects of daily changes in social distancing or virtual contact on later mental health.
We delineate a cycle wherein a daily increase in media consumption results in a subsequent increase in COVID-related worries, which in turn increases daily media consumption. Moreover, the adverse impact of news extended to broader measures of psychological struggling. A similar dynamic did not unfold between the daily amount of physical or virtual contact and subsequent mental health. Findings are consistent with current recommendations to moderate news and media consumption in order to promote mental health.
OBJECTIVES/SPECIFIC AIMS: 1) Describe strategies pediatric providers perceive improve chlamydia screening of sexually active female adolescents (SA), and 2) describe barriers to regular screening of SA for chlamydia METHODS/STUDY POPULATION: Using qualitative methods, 14 general pediatric providers across 7 clinical sites in Vermont were interviewed to ascertain best practices and remaining challenges. Semi-structured interviews lasting 30-45 minutes were audiotaped and transcribed. Chlamydia screening rates provided by BCBS-VT were used to categorize participant responses across three performance tiers, data were coded, and themes identified within these tiers. RESULTS/ANTICIPATED RESULTS: Facilitators: When asked to describe facilitators of chlamydia screening, providers in the top tier of chlamydia screening emphasized the importance of adequate insurance to cover the cost of testing. Providers in the middle performance tier cited use of pre-visit questionnaires, and those in the bottom performance tier identified no best practices. Other strategies included improving physician confidence and awareness, establishing practice- and individual-level routines, and providing strong leadership and communication of local screening rates. Barriers: Across the 3 performance tiers, the most common challenges to consistent chlamydia screening were threats to patient confidentiality, cost of the screening test, and requirement for patient disclosure of sexual activity. Less commonly, providers were concerned that adolescent patients were not reliable to obtain screens off-site, or fill treatment prescriptions without the help of a parent. DISCUSSION/SIGNIFICANCE OF IMPACT: The need for systematic, confidential, and inexpensive means for screening SA for chlamydia was highlighted in both the best practices and challenges described by providers of pediatric care in the suburban practice setting. Policy and practice interventions may target these needs to improve the reproductive health of female adolescents.
This study aimed to determine the prevalence and assemblages of Giardia duodenalis present in Scottish beef and dairy cattle at different ages, to try to ascertain if cattle could play a role in the spread of zoonotic assemblages of Giardia. A total of 388 fecal samples (128 beef and 253 dairy, seven of unknown breed) were collected from 19 farms in Scotland. Samples were sub-divided by host age, 1, 2, 3, 4, 5 and 6, 7–24 and ⩾25 weeks. DNA was extracted and tested by PCR to detect G. duodenalis DNA. Of the 388 samples, 126 tested positive, giving an overall prevalence of 32.5%, with positive samples being observed in all age groups tested. The prevalence in dairy cattle was 44.7% (113/235), which was significantly higher (P < 0.001) than the prevalence in beef cattle 10.1% (13/128). Sequence analysis demonstrated the presence of assemblage E (77.2%, sequence types E-S1–E-S5), assemblage B (18.2%) and assemblage A (sub-assemblages AI-AII) (4.6%). These data demonstrate that G. duodenalis is found routinely in both dairy and beef cattle throughout Scotland; the presence of assemblages A and B also indicates that cattle may play a role in the spread of potentially zoonotic assemblages of Giardia.
The recent revelation that there are correlated period derivative and pulse shape changes in pulsars has dramatically changed our understanding of timing noise as well as the relationship between the radio emission and the properties of the magnetosphere as a whole. Using Gaussian processes we are able to model timing and emission variability using a regression technique that imposes no functional form on the data. We revisit the pulsars first studied by Lyne et al. (2010). We not only confirm the emission and rotational transitions revealed therein, but reveal further transitions and periodicities in 8 years of extended monitoring. We also show that in many of these objects the pulse profile transitions between two well-defined shapes, coincident with changes to the period derivative. With a view to the SKA and other telescopes capable of higher cadence we also study the detection limitations of period derivative changes.
FK506 and rapamycin (Rap) are immunosuppressive drugs that act principally on T-lymphocytes. The receptors for both drugs are FK506-binding proteins (FKBPs), but the molecular mechanisms of immunosuppression differ. An FK506–FKBP complex inhibits the protein phosphatase calcineurin, blocking a key step in T-cell activation, while the Rap –FKBP complex binds to the protein kinase target of rapamycin (TOR), which is involved in a subsequent signalling pathway. Both drugs, and certain non-immunosuppressive compounds related to FK506, have potent antimalarial activity. There is however conflicting evidence on the involvement of Plasmodium calcineurin in the action of FK506, and the parasite lacks an apparent TOR homologue. We therefore set out to establish whether inhibition of the Plasmodium falciparum FKBP PfFKBP35 itself might be responsible for the antimalarial effects of FK506 and Rap. Similarities in the antiparasitic actions of FK506 and Rap would constitute indirect evidence for this hypothesis. FK506 and Rap acted indistinguishably on: (i) specificity for different intra-erythrocytic stages in culture, (ii) kinetics of killing or irreversible growth arrest of parasites and (iii) interactions with other antimalarial agents. Furthermore, PfFKBP35's inhibitory effect on calcineurin was independent of FK506 under a range of conditions, suggesting that calcineurin is unlikely to be involved in the antimalarial action of FK506.
Three-dimensional direct numerical simulations of a shearless mixing layer in a small fraction of the cloud–clear air interface are performed to study the response of an ensemble of cloud water droplets to the turbulent entrainment of clear air into a cloud filament. The main goal of this work is to understand how mixing of cloudy and clear air evolves as turbulence and thermodynamics interact through phase changes, and how the cloud droplets respond. In the main simulation case, mixing proceeds between a higher level of turbulence in the cloudy filament and a lower level of turbulence in the clear air environment – the typical shearless mixing layer set-up. Fluid turbulence is driven solely by buoyancy, which incorporates feedbacks from the temperature, the vapour content and the liquid water content fields. Two different variations on the core set of shearless mixing layer simulations are discussed, a simulation in a larger domain and a simulation with the same turbulence level inside the filament and its environment. Overall, it is found that, as evaporation occurs for the droplets that enter subsaturated clear air regions, buoyancy comes to dominate the subsequent evolution of the mixing layer. The buoyancy feedback leads initially to downdraughts at the cloudy–clear air interface and to updraughts in the bulk regions. The strength of the turbulence after initial transients depends on the domain size, showing that the range of scales is an important parameter in the shearless mixing layer set-up. In contrast, the level of turbulence in the clear air is found to have little effect on the evolution of the mixing process. The distributions of cloud water droplet size, supersaturation at the droplet positions and vertical velocity are more sensitive to domain size than to the details of the turbulence profile, suggesting that the evolution of cloud microphysics is more sensitive to large-scale as opposed to small-scale properties of the flow.
Aerogel materials manufactured from metal oxides have been used as components in numerous high-energy density physics targets. These aerogels have been identified to be used as a future target material in the AWE fielded campaigns at the US National Ignition Facility. A wide variety of metal oxide aerogels are required for future campaigns and therefore a versatile manufacturing route is sought; as such, an epoxide-assisted sol–gel route was investigated. Under the European Union Registration, Evaluation, Authorization and Restriction of Chemicals legislation, the most commonly used epoxide, propylene oxide, is recognized as a substance of very high concern (SVHC). This work sought to investigate suitable alternative epoxides for use in target manufacture. The outcome was the identification of synthesis routes for stable metal oxide aerogel monoliths using epoxides not subject to the above restrictions.
This chapter describes the karstic systems in southern Africa and explores their role in preserving records of past environmental and climatic conditions and archaeology. On longer glacial–interglacial timescales, multiproxy studies of clastic and organic cave deposits and calcium carbonate precipitates (speleothems) have provided information about the environment in which early humans lived. Speleothems also have potential to show millennial to annual-scale climate/environmental variability. The advantages of speleothems to provide precise ages, and the empirical relationships between speleothem chemistry and climate, are encouraging as we address the need for more globally dispersed terrestrial palaeoclimatic records. Future research should focus not only on obtaining more records, but also on improving the precision of data interpretation in terms of quantitative estimations of climate variables.
Cancer of unknown primary origin is a condition in which a patient has metastatic tumour without an identified primary source (NICE, 2010). Cancer of unknown primary is an imprecise term, and it is often applied to patients in whom limited investigations have been performed. To clarify this, NICE clinical guideline CG104 has used the terms ‘metastatic malignancy of uncertain origin’ (MUO), ‘provisional carcinoma of unknown primary’ (provisional CUP) and ‘confirmed carcinoma of unknown primary (confirmed CUP)’ as summarised in Table 9.1 (NICE, 2010).
For those patients whose primary tumour is identified, treatment should continue as for that individual tumour site. But if a primary tumour is not identified after the initial investigation, treatment has to be empirical and based on research in patients whose primary tumour is known. This chapter focuses on the investigation of patients presenting with malignancy of unidentified primary origin (MUO) and the treatment possibilities for those whose primary tumour is not identified after initial investigation.
Incidence and epidemiology
Cancer of unknown primary accounts for 3–5% of all invasive malignancies in the western world (Greco and Hainsworth, 2001; Pavlidis and Pentheroudakis, 2012) and ranks in the top 10 most common cancer diagnoses. In 2011, there were 9762 new cases of cancer of unknown primary diagnosed in the United Kingdom (http://www.cancerresearchuk.org/cancer-info/cancerstats/, accessed December 2014). The age-standardised rate in the UK is 10.2 per 100,000 population. The rate is higher in men than women. The incidence of cancer of unknown primary has halved in the last 20 years and most of this decrease is likely to be due to improved detection of the primary site using techniques such as histopathology, immunohistochemistry and cross-sectional imaging, which have resulted in patients not being registered as having cancer of unknown primary.
Hospital Episode Statistics (HES) data for England (06–07) recorded a total of 25,318 episodes of care for patients with a diagnosis of cancer of unknown primary representing 308,359 NHS bed-days. The majority of patients were first admitted as an emergency.
Deaths from CUP account for 7% of all cancer deaths (http://www.cancerresearchuk.org/cancer-info/cancerstats/, accessed December 2014). However, in the absence of a standard definition, the true rate may be underestimated.
An oncological emergency is an acute medical problem related to cancer or its treatment which may result in serious morbidity or mortality if not treated quickly. It may be secondary to a structural/obstructive, metabolic or treatment-related complication (Cervantes and Chirivella, 2004). The emergency may be the first manifestation of malignant disease, particularly for superior vena cava obstruction (SVCO) and malignant spinal cord compression (MSCC).
Around 20–30% of all cancer patients suffer from hypercalcaemia. Spinal cord compression is the commonest neurological complication of cancer, occuring in approximately 5–10% of all cancer patients. Thrombotic events are the second leading cause of death in cancer patients after death from cancer itself.
Types of emergency
Metabolic emergencies include:
• syndrome of inappropriate antidiuretic hormone (SIADH).
Structural/obstructive emergencies include:
• MSCC and cauda equina compression,
• raised intracranial pressure,
• acute airway obstruction,
• urinary obstruction,
• cardiac tamponade,
• pain: this has been named the ‘fifth vital sign’ following pulse, blood pressure, temperature and respiration; when pain is present it should evoke an immediate response. Treatment of pain is considered in Chapter 10 .
• thromboembolic disease.
Treatment-related emergencies include:
• neutropenic fever/sepsis,
• anaphylaxis related to a chemotherapeutic agent,
• tumour lysis syndrome,
• extravasation of a chemotherapeutic agent .
As with any acute medical emergency, resuscitation measures may be needed to ensure that airway, breathing and circulation are maintained. Adequate hydration, oxygen and monitoring of fluid balance are particularly important in patients with sepsis or tumour lysis syndrome. Steroids are used in patients with SVCO and suspected spinal cord compression, although the evidence base supporting their use is poor. Mannitol infusions may be needed for severe symptomatic raised intracranial pressure that does not respond to steroids. Pain, breathlessness and distress should be treated as priorities, especially in patients presenting with end-stage cancer and an oncological emergency. The WHO pain ladder is a suitable framework to guide appropriate analgesic use. Some seriously ill patients may need to be transferred to a high-dependency unit (HDU) or intensive therapy unit (ITU), especially those with a treatable malignancy and a good prognosis and those who develop complications of curative chemotherapy. Liaison with specialist colleagues at an early stage is recommended.
Physical health has been demonstrated to mediate the mental health and mortality risk association. The current study examines an alternative hypothesis that mental health mediates the effect of physical health on mortality risk.
Participants (N = 14,019; women = 91%), including eventual decedents (n = 3,752), were aged 70 years and older, and drawn from the Dynamic Analyses to Optimise Ageing (DYNOPTA) project. Participants were observed on two to four occasions, over a 10-year period. Mediation analysis compared the converse mediation of physical and mental health on mortality risk.
For men, neither physical nor mental health was associated with mortality risk. For women, poor mental health reported only a small effect on mortality risk (Hazard Risk (HR) = 1.01; p < 0.001); more substantive was the risk of low physical health (HR = 1.04; p < 0.001). No mediation effects were observed.
Mental health effects on mortality were fully attenuated by physical health in men, and partially so in women. Neither mental nor physical health mediated the effect of each other on mortality risk for either gender. We conclude that physical health is a stronger predictor of mortality risk than mental health.
This chapter discusses the methodological considerations surrounding linkage and association studies as well as results of both approaches as they relate to sleep and sleep disorders. The initial study of familial advanced sleep phase syndrome (FASPS) that showed it to be inherited in an autosomal dominant fashion was a linkage study on a large family with over 20 affected individuals. For the most part, the risk of narcolepsy to relatives of an affected individual is low (1-2%), albeit higher than the average population risk. Restless leg syndrome (RLS) is fairly common, with the prevalence estimated to be between 1.2 and 15% depending on the population. Complex phenotypes are influenced by multiple genetic and non-genetic factors. These phenotypes cluster in families do not follow any clear mode of inheritance. Complex phenotypes are divided into two classes: continuous and categorical. Genome-wide association study (GWAS) has been recently employed in studying sleep phenotypes.