Theoretical foundations of emergent constraints: relationships between climate sensitivity and global temperature variability in conceptual models

This is the final version. Available on open access from OUP via the DOI in this recordBackground: The emergent constraint approach has received interest recently as a way of utilizing multimodel General Circulation Model (GCM) ensembles to identify relationships between observable variations of climate and future projections of climate change. These relationships, in combination with observations of the real climate system, can be used to infer an emergent constraint on the strength of that future projection in the real system. However, there is as yet no theoretical framework to guide the search for emergent constraints. As a result, there are significant risks that indiscriminate data-mining of the multidimensional outputs from GCMs could lead to spurious correlations and less than robust constraints on future changes. To mitigate against this risk, Cox et al (hereafter CHW18) proposed a theory-motivated emergent constraint, using the one-box Hasselmann model to identify a linear relationship between equilibrium climate sensitivity (ECS) and a metric of global temperature variability involving both temperature standard deviation and autocorrelation (Ψ). A number of doubts have been raised about this approach, some concerning the application of the one-box model to understand relationships in complex GCMs which are known to have more than the single characteristic timescale. Objectives: To study whether the linear Ψ-ECS proportionality in CHW18 is an artefact of the one-box model. More precisely we ask ‘Does the linear Ψ-ECS relationship feature in the more complex and realistic two-box and diffusion models?’. Methods: We solve the two-box and diffusion models to find relationships between ECS and Ψ. These models are forced continually with white noise parameterizing internal variability. The resulting analytical relations are essentially fluctuation-dissipation theorems. Results: We show that the linear Ψ-ECS proportionality in the one-box model is not generally true in the two-box and diffusion models. However, the linear proportionality is a very good approximation for parameter ranges applicable to the current state-of-the-art CMIP5 climate models. This is not obvious - due to structural differences between the conceptual models, their predictions also differ. For example, the two-box and diffusion, unlike the one-box model, can reproduce the long term transient behaviour of the CMIP5 abrupt4xCO2 and 1pcCO2 simulations. Each of the conceptual models also predict different power spectra with only the diffusion model’s pink 1/f spectrum being compatible with observations and GCMs. We also show that the theoretically predicted Ψ-ECS relationship exists in the piControl as well as historical CMIP5 experiments and that the differing gradients of the proportionality are inversely related to the effective forcing in that experiment. Conclusions: We argue that emergent constraints should ideally be derived by such theory-driven hypothesis testing, in part to protect against spurious correlations from blind data-mining but mainly to aid understanding. In this approach, an underlying model is proposed, the model is used to predict a potential emergent relationship between an observable and an unknown future projection, and the hypothesised emergent relationship is tested against an ensemble of GCMs.European Union Horizon 2020Engineering and Physical Sciences Research Council (EPSRC)European Research Counci

Late-onset bloodstream infection and perturbed maturation of the gastrointestinal microbiota in premature infants

Late-onset bloodstream infection (LO-BSI) is a common complication of prematurity, and lack of timely diagnosis and treatment can have life-threatening consequences. We sought to identify clinical characteristics and microbial signatures in the gastrointestinal microbiota preceding diagnosis of LO-BSI in premature infants.Daily faecal samples and clinical data were collected over two years from 369 premature neonates (<32 weeks gestation). We analysed samples from 22 neonates who developed LO-BSI and 44 matched control infants. Next-generation sequencing of 16S rRNA gene regions amplified by PCR from total faecal DNA was used to characterise the microbiota of faecal samples preceding diagnosis from infants with LO-BSI and controls. Culture of selected samples was undertaken, and bacterial isolates identified using MALDI-TOF. Antibiograms from bloodstream and faecal isolates were compared to explore strain similarity.From the week prior to diagnosis, infants with LO-BSI had higher proportions of faecal aerobes/facultative anaerobes compared to controls. Risk factors for LO-BSI were identified by multivariate analysis. Enterobacteriaceal sepsis was associated with antecedent multiple lines, low birth weight and a faecal microbiota with prominent Enterobacteriaceae. Staphylococcal sepsis was associated with Staphylococcus OTU faecal over-abundance, and the number of days prior to diagnosis of mechanical ventilation and of the presence of centrally-placed lines. In 12 cases, the antibiogram of the bloodstream isolate matched that of a component of the faecal microbiota in the sample collected closest to diagnosis.The gastrointestinal tract is an important reservoir for LO-BSI organisms, pathogens translocating across the epithelial barrier. LO-BSI is associated with an aberrant microbiota, with abundant staphylococci and Enterobacteriaceae and a failure to mature towards predominance of obligate anaerobes

(In)Dependence, Socio-sexual Relationships, and Sexual Health Among Adults with Mild Intellectual Disability (MID): A Critical, Qualitative Exploration

The purpose of this critical, qualitative study was to explore how adults with mild intellectual disability navigate independent socio-sexual relationships in settings where they are highly dependent upon caregivers and family members who exert significant control over most aspects of their lives. Data were gathered during one-on-one interviews conducted with adults with MID (n=15), and parental caregivers (n=6). Theoretical insights from critical disability studies and sexual citizenship were used to analyze the findings, which are presented thematically by study population. Participants with MID faced challenges to establishing and maintaining meaningful relationships, including a lack of choice about where and how they interact with others, a lack of privacy for intimacy, and not being afforded adequate knowledge of healthy relationships and sexual health by their caregivers. These challenges were directly shaped by the perspectives of caregivers, who perceived their adult children with MID as being inherently vulnerable and in need of their intervention. Their intervention often took the form of paternalistic practices that curtailed the activities and aspirations related to day-to-day life activities, peer-relationships, and sexuality for the adults with MID. These study findings contribute fresh, compelling insights to this important research, especially in relation to the topics of assumed vulnerability, sexual boundaries, sexual violence, and reproduction among adults with MID. The potential impact of these data on disability policies and practices, particularly those that affect the social, spatial, and sexual health of adults with MID are discussed, and recommendations for policy and advocacy are offered

Evaluating classification accuracy for modern learning approaches

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149333/1/sim8103_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149333/2/sim8103.pd

Point-of-care screening for a current Hepatitis C virus infection: influence on uptake of a concomitant offer of HIV screening

Eliminating hepatitis C as a public health threat requires an improved understanding of how to increase testing uptake. We piloted point-of-care testing (POCT) for a current HCV infection in an inner-city Emergency Department (ED) and assessed the influence on uptake of offering concomitant screening for HIV. Over four months, all adults attending ED with minor injuries were first invited to complete an anonymous questionnaire then invited to test in alternating cycles offering HCV POCT or HCV+HIV POCT. Viral RNA was detected in finger-prick blood by GeneXpert. 814/859 (94.8%) questionnaires were returned and 324/814 (39.8%) tests were accepted, comprising 211 HCV tests and 113 HCV+HIV tests. Offering concomitant HIV screening reduced uptake after adjusting for age and previous HCV testing (odds ratio 0.51; 95% confidence interval [CI] 0.38–0.68; p < 0.001). HCV prevalence was 1/324 (0.31%; 95% CI 0.05–1.73); no participant tested positive for HIV. 167/297 (56.2%) POCT participants lived in the most deprived neighbourhoods in England. HCV RNA testing using finger-prick blood was technically feasible. Uptake was moderate and the offer of concomitant HIV screening showed a detrimental impact on acceptability in this low prevalence population. The findings should be confirmed in a variety of other community settings

The trans-contextual model: Perceived learning and performance motivational climates as analogues of perceived autonomy support

The trans-contextual model of motivation (TCM) proposes that perceived autonomy support in physical education (PE) predicts autonomous motivation within this context, which, in turn, is related to autonomous motivation and physical activity in leisure-time. According to achievement goal theory perceptions of learning and performance, motivational climate in PE can also affect autonomous motivation in PE. The purpose of the present study was to examine the influence of an integrated approach of perceptions of motivational climate in PE by incorporating aspects of perceptions of motivational climate from achievement goal frameworks on autonomous motivation in PE within the TCM. High school students (N = 274) completed self-report measures of perceived autonomy support, perceived learning, and performance motivational climate and autonomous motivation in PE. Follow-up measures of autonomous motivation in a leisure-time context were taken along with measures of attitudes, subjective norms, perceived behavioural control and intentions from the theory of planned behaviour 1 week later. Self-reported physical activity behaviour was measured 5 weeks later. The results of the path analyses indicated that perceived learning climate was the strongest predictor of autonomous motivation in PE and leisure-time contexts and mediated the effect of perceived autonomy support on autonomous motivation in PE. Perceived performance climate showed no significant effect on autonomous motivation in PE and leisure-time. Results also confirmed the premises of TCM regarding the effect of autonomous motivation in leisure-time on leisure-time physical activity and the mediating role of the planned behaviour theory variables

Predicting the risk of Chronic Kidney Disease in Men and Women in England and Wales: prospective derivation and external validation of the QKidney® Scores

<p>Abstract</p> <p>Background</p> <p>Chronic Kidney Disease is a major cause of morbidity and interventions now exist which can reduce risk. We sought to develop and validate two new risk algorithms (the QKidney^®Scores) for estimating (a) the individual 5 year risk of moderate-severe CKD and (b) the individual 5 year risk of developing End Stage Kidney Failure in a primary care population.</p> <p>Methods</p> <p>We conducted a prospective open cohort study using data from 368 QResearch^®general practices to develop the scores. We validated the scores using two separate sets of practices - 188 separate QResearch^®practices and 364 practices contributing to the THIN database.</p> <p>We studied 775,091 women and 799,658 men aged 35-74 years in the QResearch^®derivation cohort, who contributed 4,068,643 and 4,121,926 person-years of observation respectively.</p> <p>We had two main outcomes (a) moderate-severe CKD (defined as the first evidence of CKD based on the earliest of any of the following: kidney transplant; kidney dialysis; diagnosis of nephropathy; persistent proteinuria; or glomerular filtration rate of < 45 mL/min) and (b) End Stage Kidney Failure.</p> <p>We derived separate risk equations for men and women. We calculated measures of calibration and discrimination using the two separate validation cohorts.</p> <p>Results</p> <p>Our final model for moderate-severe CKD included: age, ethnicity, deprivation, smoking, BMI, systolic blood pressure, diabetes, rheumatoid arthritis, cardiovascular disease, treated hypertension, congestive cardiac failure; peripheral vascular disease, NSAID use and family history of kidney disease. In addition, it included SLE and kidney stones in women. The final model for End Stage Kidney Failure was similar except it did not include NSAID use.</p> <p>Each risk prediction algorithms performed well across all measures in both validation cohorts. For the THIN cohort, the model to predict moderate-severe CKD explained 56.38% of the total variation in women and 57.49% for men. The D statistic values were high with values of 2.33 for women and 2.38 for men. The ROC statistic was 0.875 for women and 0.876 for men.</p> <p>Conclusions</p> <p>These new algorithms have the potential to identify high risk patients who might benefit from more detailed assessment, closer monitoring or interventions to reduce their risk.</p

Socio-economic variation in CT scanning in Northern England, 1990-2002

<p>Abstract</p> <p>Background</p> <p>Socio-economic status is known to influence health throughout life. In childhood, studies have shown increased injury rates in more deprived settings. Socio-economic status may therefore be related to rates of certain medical procedures, such as computed tomography (CT) scans. This study aimed to assess socio-economic variation among young people having CT scans in Northern England between 1990 and 2002 inclusive.</p> <p>Methods</p> <p>Electronic data were obtained from Radiology Information Systems of all nine National Health Service hospital Trusts in the region. CT scan data, including sex, date of scan, age at scan, number and type of scans were assessed in relation to quintiles of Townsend deprivation scores, obtained from linkage of postcodes with census data, using χ²tests and Spearman rank correlations.</p> <p>Results</p> <p>During the study period, 39,676 scans were recorded on 21,089 patients, with 38,007 scans and 19,485 patients (11344 male and 8132 female) linkable to Townsend scores. The overall distributions of both scans and patients by quintile of Townsend deprivation scores were significantly different to the distributions of Townsend scores from the census wards included in the study (p < 0.0001). There was a significant association between type of scan and deprivation quintile (p < 0.0001), primarily due to the higher proportions of head scans in the three most deprived quintiles, and slightly higher proportions of chest scans and abdomen and pelvis scans in the least deprived groups. There was also a significant association (p < 0.0001) between the patient's age at the time of the CT scan and Townsend deprivation quintiles, with slightly increasing proportions of younger children with increasing deprivation. A similar association with age (p < 0.0001) was seen when restricting the data to include only the first scan of each patient. The number of scans per patient was also associated with Townsend deprivation quintiles (p = 0.014).</p> <p>Conclusions</p> <p>Social inequalities exist in the numbers of young people undergoing CT scans with those from deprived areas more likely to do so. This may reflect the rates of injuries in these individuals and implies that certain groups within the population may receive higher radiation doses than others due to medical procedures.</p

The priB Gene of Klebsiella pneumoniae Encodes a 104-Amino Acid Protein That Is Similar in Structure and Function to Escherichia coli PriB

Primosome protein PriB is a single-stranded DNA-binding protein that serves as an accessory factor for PriA helicase-catalyzed origin-independent reinitiation of DNA replication in bacteria. A recent report describes the identification of a novel PriB protein in Klebsiella pneumoniae that is significantly shorter than most sequenced PriB homologs. The K. pneumoniae PriB protein is proposed to comprise 55 amino acid residues, in contrast to E. coli PriB which comprises 104 amino acid residues and has a length that is typical of most sequenced PriB homologs. Here, we report results of a sequence analysis that suggests that the priB gene of K. pneumoniae encodes a 104-amino acid PriB protein, akin to its E. coli counterpart. Furthermore, we have cloned the K. pneumoniae priB gene and purified the 104-amino acid K. pneumoniae PriB protein. Gel filtration experiments reveal that the K. pneumoniae PriB protein is a dimer, and equilibrium DNA binding experiments demonstrate that K. pneumoniae PriB's single-stranded DNA-binding activity is similar to that of E. coli PriB. These results indicate that the PriB homolog of K. pneumoniae is similar in structure and in function to that of E. coli