We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure coreplatform@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Clinical trials that fail prematurely due to poor design are a waste of resources and deprives us of data for evaluating potentially effective interventions. This study used machine learning modelling to predict clinical trials’ success or failure and to understand feature contributions driving this result. Features to power the modelling were engineered using data collected from the National Institute for Health and Care Research Innovation Observatory’s ScanMedicine database.
Methods
Using ScanMedicine, a large dataset containing 641,079 clinical trial records from 11 global clinical trial registries, was extracted. Sixteen features were generated from the data based on fields relating to trial design and eligibility. Trials were labeled positive if they were completed (or target recruitment was achieved) or negative if terminated/withdrawn (or target recruitment was not achieved). To achieve optimal performance, phase-specific datasets were generated, and we focused on a subsample of Phase 2 trials (n=70,167). Ensemble models using bagging and boosting algorithms, including balanced random forest and extreme gradient boosting classifiers were used for training and evaluating predictive performance. Shapley Additive Explanations was used to explain the output of the best performing model and calculate feature contributions for individual studies.
Results
We achieved a weighted F1-score of 0.88, Receiver Operator Characteristic Area under the Curve score of 0.75, and balanced accuracy of 0.75 on the test set with the xgBoost model. This result shows that the model can successfully distinguish between classes to predict if a trial will succeed or fail and subsequently output the features driving this outcome. The number of primary outcomes, whether the study was randomized, target sample size and number of exclusion criteria were the most important features affecting the model’s prediction.
Conclusions
This study is the first to use predictive modelling on a large sample of clinical trial data obtained from 11 international trial registries. The prediction outcomes achieved by our novel approach, which uses phase-specific trained models, outperforms previous modelling in this space.
The introduction pursues three aims: it examines the problems of representing beginnings in literary history in general; it explains the value of a literary history that focuses on the beginnings, rather than the subsequent development, of vernacular literatures in medieval Europe; and it describes the advantages of a comparative approach. In respect of the first aim, it argues that we should neither posit a unitary beginning for literature in any language nor think in terms of causes and effects: every literary tradition passes through multiple moments of incipience and opening, and their study reveals conditions of possibility, not mechanistic causes. Second, a concentration on beginning obliges us to define what begins, thereby bringing to light the distinctive features of each vernacular literature. Third, the comparative perspective reveals the matrix of defining characteristics that the nascent European literatures of the Middle Ages all share: their manuscript materiality, their institutionalization in systems of textual practice which confer stability and persistence in space and time, and, finally, their linguistic vernacularity, which defines them over against their respective ‘parental’ literacies in Latin, Greek, or Church Slavonic.
This chapter surveys the formation of German vernacular literature between the ninth and thirteenth centuries. Instead of one single beginning, from which all the rest flows, we encounter a series of inaugural gestures and moments of inception, not all of which extended into posterity. The great monuments of Old High German literature, produced in the ninth century, are isolated works that did not give rise to continuous traditions of textual production; for that development, we have to wait until the second half of the eleventh century, when an astonishingly self-assured and formally sophisticated literature – now linguistically Middle High German – burst onto the scene. In the course of the twelfth century, religious genres were joined by secular ones, and the pragmatic functions of informing and instructing the public were supplemented by an interest in the potentialities of poetic language and distinctly literary modes of cognition. Finally, by the early thirteenth century, a palpable sense had emerged among collectors and authors that German literature has both a canon and a history; the constitution of manuscript anthologies and literary genealogies represents a further beginning in the formation of German literature as a dynamic system, as well as itself positing beginnings.
How did new literatures begin in the Middle Ages and what does it mean to ask about such beginnings? These are the questions this volume pursues across the regions and languages of medieval Europe, from Iceland, Scandinavia, and Iberia through Irish, Welsh, English, French, Dutch, Occitan, German, Italian, Czech, and Croatian to Medieval Greek and the East Slavonic of early Rus. Focusing on vernacular scripted cultures and their complicated relationships with the established literary cultures of Latin, Greek, and Church Slavonic, the volume's contributors describe the processes of emergence, consolidation, and institutionalization that make it possible to speak of a literary tradition in any given language. Moreover, by concentrating on beginnings, the volume avoids the pitfalls of viewing earlier phenomena through the lens of later, national developments; the result is a heightened sense of the historical contingency of categories of language, literature, and territory in the space we call 'Europe'.
Among outpatients with coronavirus disease 2019 (COVID-19) due to the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) δ (delta) variant who did and did not receive 2 vaccine doses at 7 days after symptom onset, there was no difference in viral shedding (cycle threshold difference 0.59, 95% CI, −4.68 to 3.50; P = .77) with SARS-CoV-2 cultured from 2 (7%) of 28 and 1 (4%) of 26 outpatients, respectively.
Multiple micronutrient deficiencies are widespread in Ethiopia. However, the distribution of Se and Zn deficiency risks has previously shown evidence of spatially dependent variability, warranting the need to explore this aspect for wider micronutrients. Here, blood serum concentrations for Ca, Mg, Co, Cu and Mo were measured (n 3102) on samples from the Ethiopian National Micronutrient Survey. Geostatistical modelling was used to test spatial variation of these micronutrients for women of reproductive age, who represent the largest demographic group surveyed (n 1290). Median serum concentrations were 8·6 mg dl−1 for Ca, 1·9 mg dl−1 for Mg, 0·4 µg l−1 for Co, 98·8 µg dl−1 for Cu and 0·2 µg dl−1 for Mo. The prevalence of Ca, Mg and Co deficiency was 41·6 %, 29·2 % and 15·9 %, respectively; Cu and Mo deficiency prevalence was 7·6 % and 0·3 %, respectively. A higher prevalence of Ca, Cu and Mo deficiency was observed in north western, Co deficiency in central and Mg deficiency in north eastern parts of Ethiopia. Serum Ca, Mg and Mo concentrations show spatial dependencies up to 140–500 km; however, there was no evidence of spatial correlations for serum Co and Cu concentrations. These new data indicate the scale of multiple mineral micronutrient deficiency in Ethiopia and the geographical differences in the prevalence of deficiencies suggesting the need to consider targeted responses during the planning of nutrition intervention programmes.
We study the classical Hermite–Hadamard inequality in the matrix setting. This leads to a number of interesting matrix inequalities such as the Schatten p-norm estimates
Adhering to a Mediterranean diet (MD) is associated with reduced CVD risk. This study aimed to explore methods of increasing MD adoption in a non-Mediterranean population at high risk of CVD, including assessing the feasibility of a developed peer support intervention. The Trial to Encourage Adoption and Maintenance of a MEditerranean Diet was a 12-month pilot parallel group RCT involving individuals aged ≥ 40 year, with low MD adherence, who were overweight, and had an estimated CVD risk ≥ 20 % over ten years. It explored three interventions, a peer support group, a dietician-led support group and a minimal support group to encourage dietary behaviour change and monitored variability in Mediterranean Diet Score (MDS) over time and between the intervention groups, alongside measurement of markers of nutritional status and cardiovascular risk. 118 individuals were assessed for eligibility, and 75 (64 %) were eligible. After 12 months, there was a retention rate of 69 % (peer support group 59 %; DSG 88 %; MSG 63 %). For all participants, increases in MDS were observed over 12 months (P < 0·001), both in original MDS data and when imputed data were used. Improvements in BMI, HbA1c levels, systolic and diastolic blood pressure in the population as a whole. This pilot study has demonstrated that a non-Mediterranean adult population at high CVD risk can make dietary behaviour change over a 12-month period towards an MD. The study also highlights the feasibility of a peer support intervention to encourage MD behaviour change amongst this population group and will inform a definitive trial.
Anorexia nervosa (AN) is characterized by an overgeneralization of food/body-related autobiographical memories (AM). This is regarded as an emotion regulation strategy with adverse long-term effects implicated in disorder maintenance and treatment resistance. Therefore, we aimed to examine neural correlates of food/body-related AM-recall in AN.
Methods
Twenty-nine female patients with AN and 30 medication-free age-sex-matched normal-weight healthy controls (HC) underwent functional magnetic resonance imaging while recalling AMs in response to food/body-related and neutral cue words. To control for general knowledge retrieval, participants engaged in a semantic generation and riser detection task.
Results
In comparison to HC, patients with AN generated fewer and less specific AMs in response to food/body-related words, but not for neutral cue words. Group comparisons revealed reduced activation in regions associated with self-referential processing and memory retrieval (precuneus and angular gyrus) during the retrieval of specific food/body-related AM in patients with AN. Brain connectivity in regions associated with memory functioning and executive control was reduced in patients with AN during the retrieval of specific food/body-related AM. Finally, resting-state functional connectivity analysis revealed no differences between groups, arguing against a general underlying disconnection of brain networks implicated in memory and emotional processing in AN.
Conclusions
These results indicate impaired neural processing of food/body-related AM in AN, with a reduced involvement of regions involved in self-referential processing. Our findings are discussed as possible neuronal correlates of emotional avoidance in AN and provide new insights of AN-pathophysiology underscoring the importance of targeting dysfunctional emotion regulation strategies during treatment.
ABSTRACT IMPACT: This study is designed to address a critical gap in our understanding of how aging patients and caregivers recognize and respond to clinically important changes in heart failure symptoms during vulnerable transitions. OBJECTIVES/GOALS: Research on family involvement in heart failure (HF) symptom response is limited. Our objective is to examine HF symptom monitoring processes in couples after HF hospitalization, and quantify how coupled symptom assessments predict symptom response, patient clinical events, care strain, and dyad health during the high-risk post-discharge period. METHODS/STUDY POPULATION: This is an ongoing T2 translational study that employs an intensive longitudinal design. Adults aged ≥65 years hospitalized for HF and their caregiving spouse/partner are enrolled. The target n is 48 dyads. Over 5 weeks of follow-up, dyads complete daily diaries assessing patient HF symptoms. Clinical biomarkers of HF severity (NTproBNP, ST2) are also collected. Primary study endpoints are dyads’ HF symptom response behaviors and caregiver strain; secondary endpoints are dyads’ health status and patient clinical events. Dyadic dynamics of symptom assessment will first be characterized using dyadic autoregressive time series models. Subsequently, we will extract cross-partner effect parameters from the time series models and test whether dyadic effects predict the trajectories of each of our endpoints. RESULTS/ANTICIPATED RESULTS: This study is currently underway. In line with our study hypotheses, we anticipate that couples who assess patient symptoms similarly (dyadic agreement), and whose symptom assessments accurately reflect clinical severity, will be more likely to respond to symptoms appropriately with lower stress to the caregiving partner, and have better trajectories of health (self-reported and clinical). Characterizing dyadic symptom dynamics will provide important insight into the day-to-day process of symptom recognition in couples. Further, quantifying dyadic symptom dynamics in relation to our endpoints will provide information on the clinical value of dyadic symptom agreement, and whether it might be a target for future interventions to support better symptom response and health outcomes for both dyad members. DISCUSSION/SIGNIFICANCE OF FINDINGS: This project innovates on existing paradigms by applying family-level theory and techniques to better understand and support interventions for couples during post-discharge HF transitions - a vulnerable period for older adults that has traditionally been studied almost exclusively at the patient-level, with marginal success.
The longitudinal relationship between depression and the risk of non-alcoholic fatty liver disease is uncertain. We examined: (a) the association between depressive symptoms and incident hepatic steatosis (HS), both with and without liver fibrosis; and (b) the influence of obesity on this association.
Methods
A cohort of 142 005 Korean adults with neither HS nor excessive alcohol consumption at baseline were followed for up to 8.9 years. The validated Center for Epidemiologic Studies-Depression score (CES-D) was assessed at baseline, and subjects were categorised as non-depressed (a CES-D < 8, reference) or depression (CES-D ⩾ 16). HS was diagnosed by ultrasonography. Liver fibrosis was assessed by the fibrosis-4 index (FIB-4). Parametric proportional hazards models were used to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).
Results
During a median follow-up of 4.0 years, 27 810 people with incident HS and 134 with incident HS plus high FIB-4 were identified. Compared with the non-depressed category, the aHR (95% CIs) for incident HS was 1.24 (1.15–1.34) for CES-D ⩾ 16 among obese individuals, and 1.00 (0.95–1.05) for CES-D ⩾ 16 among non-obese individuals (p for interaction with obesity <0.001). The aHR (95% CIs) for developing HS plus high FIB-4 was 3.41 (1.33–8.74) for CES-D ⩾ 16 among obese individuals, and 1.22 (0.60–2.47) for CES-D ⩾ 16 among non-obese individuals (p for interaction = 0.201).
Conclusions
Depression was associated with an increased risk of incident HS and HS plus high probability of advanced fibrosis, especially among obese individuals.
Widespread testing for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) is necessary to curb the spread of coronavirus disease 2019 (COVID-19), but testing is undermined when the only option is a nasopharyngeal swab. Self-collected swab techniques can overcome many of the disadvantages of a nasopharyngeal swab, but they require evaluation.
Methods:
Three self-collected non-nasopharyngeal swab techniques (saline gargle, oral swab and combined oral-anterior nasal swab) were compared to a nasopharyngeal swab for SARS-CoV-2 detection at multiple COVID-19 assessment centers in Toronto, Canada. The performance characteristics of each test were assessed.
Results:
The adjusted sensitivity of the saline gargle was 0.90 (95% CI 0.86-0.94), the oral swab was 0.82 (95% CI, 0.72–0.89) and the combined oral–anterior nasal swab was 0.87 (95% CI, 0.77–0.93) compared to a nasopharyngeal swab, which demonstrated a sensitivity of ˜90% when all positive tests were the reference standard. The median cycle threshold values for the SARS-CoV-2 E-gene for concordant and discordant saline gargle specimens were 17 and 31 (P < .001), for the oral swabs these values were 17 and 28 (P < .001), and for oral–anterior nasal swabs these values were 18 and 31 (P = .007).
Conclusions:
Self-collected saline gargle and an oral–anterior nasal swab have a similar sensitivity to a nasopharyngeal swab for the detection of SARS-CoV-2. These alternative collection techniques are cheap and can eliminate barriers to testing, particularly in underserved populations.
We obtain several norm and eigenvalue inequalities for positive matrices partitioned into four blocks. The results involve the numerical range $W(X)$ of the off-diagonal block $X$, especially the distance $d$ from $0$ to $W(X)$. A special consequence is an estimate,
Introduction: Postpartum weight management is difficult for many mothers due to the demands of parenthood. Women have highlighted a need for support but experience barriers to engaging with lifestyle interventions hence more adaptable approaches are required. This work examined participants’ engagement with a 12-month, theory-based, automated, text message (SMS) delivered, intervention supporting postpartum weight management.
Methods: SMS content was informed by: 1) the ‘Health Action Process Approach’ (HAPA)1; 2) behaviour change techniques associated with effectiveness in weight management interventions2; 3) women's accounts of postpartum weight-related experiences; and 4) personal and public involvement. A two-arm pilot RCT recruited women within two years postpartum, with a BMI ≥ 25 kg/m2, through community sources and social media. Women were randomised via a secure remote system to receive the intervention or an active control delivering child development messages. Participants received 353 messages during the 12 month intervention. Two-way messages were used to assess engagement: 50 messages prompted women to respond with their weight; 36 interactive messages requested participants’ to respond ‘Yes/No’ to a question which then triggered a feedback message. Participant engagement with two-way messages was calculated as a percentage of replies sent by women and was categorised as ‘high’ or ‘low’ according to the median number of replies sent. Weight was measured at 0, 3, 6, 9 and 12 months.
Results: 51 of 100 women recruited were randomised to receive the intervention. In months 0–6, (47%) and (95%) of participants responded to the weight messages and the ‘Yes/No’ messages respectively. In months 7–12, the responses were (77%) and (86%) respectively. Participants who were high engagers with weight messages had greater mean weight loss compared with low engagers at all time points: at 12 months high engagers (n = 18) lost -2.66 kg and had a reduction in waist circumference at 12 months of -8.9 cm, compared to changes in low engagers (n = 18) of -0.84 kg and -3.6 cm. Likewise, high engagers with ‘Yes/No’ messages had greater mean weight loss compared with low engagers at all time points: at 12 months high engagers (n = 16) lost -2.87 kg and had a reduction in waist circumference of -9.4 cm, compared to changes in low engagers (n = 20) of -0.86 kg and -3.6 cm.
Discussion: The use of two-way text messages was a useful way to encourage engagement with this SMS-delivered intervention. Higher engagement resulted in more weight loss compared to low engagement.