Translating HbA1c measurements into estimated average glucose values in pregnant women with diabetes

Aims/hypothesis This study aimed to examine the relationship between average glucose levels, assessed by continuous glucose monitoring (CGM), and HbA1c levels in pregnant women with diabetes to determine whether calculations of standard estimated average glucose (eAG) levels from HbA1c measurements are applicable to pregnant women with diabetes. Methods CGM data from 117 pregnant women (89 women with type 1 diabetes; 28 women with type 2 diabetes) were analysed. Average glucose levels were calculated from 5–7 day CGM profiles (mean 1275 glucose values per profile) and paired with a corresponding (±1 week) HbA1c measure. In total, 688 average glucose–HbA1c pairs were obtained across pregnancy (mean six pairs per participant). Average glucose level was used as the dependent variable in a regression model. Covariates were gestational week, study centre and HbA1c. Results There was a strong association between HbA1c and average glucose values in pregnancy (coefficient 0.67 [95% CI 0.57, 0.78]), i.e. a 1% (11 mmol/mol) difference in HbA1c corresponded to a 0.67 mmol/l difference in average glucose. The random effects model that included gestational week as a curvilinear (quadratic) covariate fitted best, allowing calculation of a pregnancy-specific eAG (PeAG). This showed that an HbA1c of 8.0% (64 mmol/mol) gave a PeAG of 7.4–7.7 mmol/l (depending on gestational week), compared with a standard eAG of 10.2 mmol/l. The PeAG associated with maintaining an HbA1c level of 6.0% (42 mmol/mol) during pregnancy was between 6.4 and 6.7 mmol/l, depending on gestational week. Conclusions/interpretation The HbA1c–average glucose relationship is altered by pregnancy. Routinely generated standard eAG values do not account for this difference between pregnant and non-pregnant individuals and, thus, should not be used during pregnancy. Instead, the PeAG values deduced in the current study are recommended for antenatal clinical care

Measures to Control Harmful Algal Blooms

Harmful algal blooms (HABs) occur globally and are caused by different species of microalgae. They can be harmful by producing toxins or by the rapid increase in biomass often leading to discoloration and hypoxic conditions. Toxins accumulating in shellfish and fish can cause shellfish poisoning in humans, major economical losses, especially damage to aquaculture, and affects on marine life. Bloom events are natural phenomena and have been reported for centuries but the recent increase in blooms and their global spread, which are often discussed in relation to human influences, has caused concern. In the absence of reducing such factors, controlling blooms and mitigating effects are essential. Here, methods of controlling HABs by directly targeting the causative algae are reviewed. Studies have shown many possible control measures, biological, chemical and physical, but many methods are restricted by cost, practicality and environmental toxicity. Research on mortality and cell lysis of algae in the wild has lead to studies on biological control by bottom-up and top-down control, but no achievable method has yet been suggested. Flocculation by clay appears promising and is currently used in some areas, but global use is restricted for practical and economical reasons. Many chemicals have also been suggested of which surfactants have received recent attention. Toxicity tests on other, non-target marine organisms are necessary before such chemicals can be considered for use in the field. In the absence of successful control measures, mitigation to minimize effects is often important and widely employed

Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention

Application of real-time global media monitoring and ‘derived questions’ for enhancing communication by regulatory bodies:the case of human papillomavirus vaccines

Abstract Background The benefit-risk balance of vaccines is regularly debated by the public, but the utility of media monitoring for regulatory bodies is unclear. A media monitoring study was conducted at the European Medicines Agency (EMA) concerning human papillomavirus (HPV) vaccines during a European Union (EU) referral procedure assessing the potential causality of complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS) reported to the authorities as suspected adverse reactions. Methods To evaluate the utility of media monitoring in real life, prospective real-time monitoring of worldwide online news was conducted from September to December 2015 with inductive content analysis, generating ‘derived questions’. The evaluation was performed through the validation of the predictive capacity of these questions against journalists’ queries, review of the EMA’s public statement and feedback from EU regulators. Results A total of 4230 news items were identified, containing personal stories, scientific and policy/process-related topics. Explicit and implicit concerns were identified, including those raised due to lack of knowledge or anticipated once more information would be published. Fifty derived questions were generated and categorised into 12 themes. The evaluation demonstrated that providing the media monitoring findings to assessors and communicators resulted in (1) confirming that public concerns regarding CRPS and POTS would be covered by the assessment; (2) meeting specific information needs proactively in the public statement; (3) predicting all queries from journalists; and (4) altering the tone of the public statement with respectful acknowledgement of the health status of patients with CRSP or POTS. Conclusions The study demonstrated the potential utility of media monitoring for regulatory bodies to support communication proactivity and preparedness, intended to support trusted safe and effective vaccine use. Derived questions seem to be a familiar and effective format for presenting media monitoring results in the scientific-regulatory environment. It is suggested that media monitoring could form part of regular surveillance for medicines of high public interest. Future work is recommended to develop efficient monitoring strategies for that purpose

Cardiac output during exercise related to plasma atrial natriuretic peptide but not to central venous pressure in humans.

NEW FINDINGS: What is the central question of this study? Is cardiac output during exercise dependent on central venous pressure? What is the main finding and its importance? The increase in cardiac output during both rowing and running is related to preload to the heart as indicated by plasma atrial natriuretic peptide but unrelated to central venous pressure. The results indicate that in upright humans central venous pressure reflects the gravitational influence on central venous blood rather than preload to the heart. ABSTRACT: Aim This study evaluated the increase in cardiac output (CO) during exercise in relation to central venous pressure (CVP) and plasma arterial natriuretic peptide (ANP) as expressions of preload to the heart. Methods Seven healthy subjects (four men; 26 ± 3 years; 181± 8 cm height; and 76 ± 11 kg, weight; mean ± SD) rested in sitting and standing positions (in randomized order) and then rowed and ran at submaximal workloads. The CVP was recorded, CO (Modelflow) calculated, and arterial plasma ANP determined by radioimmunoassay. Results While sitting CO was 6.2 ± 1.6 l/min, plasma ANP 70 ± 10 pg/ml, and CVP 1.8 ± 1.1 mmHg (mean ± SD) and decreased to 5.9 ± 1.0 l/min, 63 ± 10 pg/ml, and -3.8 ± 1.2 mmHg, respectively when standing (P < 0.05). Ergometer rowing elicited an increase in CO to 22.5 ± 5.5 l/min as plasma ANP increased to 156 ± 11 pg/ml and CVP to 3.8 ± 0.9 mmHg (P < 0.05). Similarly, CO increased to 23.5 ± 6.0 l/min during running with albeit smaller (P < 0.05) increase in plasma ANP, but with little change in CVP (-0.9 ± 0.4 mmHg). Conclusion The increase in CO in response to exercise is related to preload to the heart as indicated by plasma ANP, but unrelated to CVP. The results indicate that in upright humans CVP reflects the gravitational influence on central venous blood rather than preload to the heart. This article is protected by copyright. All rights reserved

Application of real-time global media monitoring and ‘derived questions’ for enhancing communication by regulatory bodies:the case of human papillomavirus vaccines

Abstract Background The benefit-risk balance of vaccines is regularly debated by the public, but the utility of media monitoring for regulatory bodies is unclear. A media monitoring study was conducted at the European Medicines Agency (EMA) concerning human papillomavirus (HPV) vaccines during a European Union (EU) referral procedure assessing the potential causality of complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS) reported to the authorities as suspected adverse reactions. Methods To evaluate the utility of media monitoring in real life, prospective real-time monitoring of worldwide online news was conducted from September to December 2015 with inductive content analysis, generating ‘derived questions’. The evaluation was performed through the validation of the predictive capacity of these questions against journalists’ queries, review of the EMA’s public statement and feedback from EU regulators. Results A total of 4230 news items were identified, containing personal stories, scientific and policy/process-related topics. Explicit and implicit concerns were identified, including those raised due to lack of knowledge or anticipated once more information would be published. Fifty derived questions were generated and categorised into 12 themes. The evaluation demonstrated that providing the media monitoring findings to assessors and communicators resulted in (1) confirming that public concerns regarding CRPS and POTS would be covered by the assessment; (2) meeting specific information needs proactively in the public statement; (3) predicting all queries from journalists; and (4) altering the tone of the public statement with respectful acknowledgement of the health status of patients with CRSP or POTS. Conclusions The study demonstrated the potential utility of media monitoring for regulatory bodies to support communication proactivity and preparedness, intended to support trusted safe and effective vaccine use. Derived questions seem to be a familiar and effective format for presenting media monitoring results in the scientific-regulatory environment. It is suggested that media monitoring could form part of regular surveillance for medicines of high public interest. Future work is recommended to develop efficient monitoring strategies for that purpose

Living with the dilemma of the treatment for human epidermal growth factor receptor 2-positive breast cancer and the risk of incident heart disease:A qualitative investigation of patients' experiences

Objective: Herceptin treatment improves survival and reduces the risk of recurrence in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Yet, it increases women's risk of developing burdensome cardiovascular complications. This study examines how women experience living with HER2-positive breast cancer and the risk of incident heart disease. Methods: Danish women with breast cancer (n = 12; aged 32–75) participated in semi-structured interviews. Themes were deducted using interpretative phenomenological analysis (IPA). Results: Women described breast cancer as having strong associations with death, whereas heart disease to them meant decreased physical functioning or “something fixable.” MUGA scans of the heart during the treatment course made them feel safe, and generally, they did not worry about risk of heart disease. Coping strategies included the following: focus on the good aspects of herceptin and acceptance of risk of heart disease as the price to pay to survive. The two most predominant coping strategies used were information and avoidance. Conclusion: The women's focus on cancer as the primary disease seems partly to be the result of a complex coping process, by which they dealt with the dilemma of weighing risks, where the risk of dying from breast cancer was perceived as the biggest risk.</p

Assessing Cognitive and Social Awareness among Group Members in AI-assisted Collaboration

Successful collaboration in computer-mediated teams requires awareness among group members of each other’s knowledge, skills, and goals. Large Language Models (LLMs) can play a mediating role in establishing and maintaining this awareness among group members. In an in-situ study, we explored the impact of an LLM-based chatbot on cognitive and social group awareness through a distributed text-based group task. We instructed participants (N = 48) to complete a travel-planning task in sixteen groups of three, with each member given conflicting goals. Each chat was complemented by a chatbot that could be asked for assistance. Through a survey and semi-structured interview, we gained insight into participants’ deliberations on the task and the chatbot’s role. We found that the chatbot’s presence helped increase group awareness as users are forced to clearly and transparently formulate their intentions when prompting the chatbot. The chatbot’s ability to provide suggestions that compromise between user goals based on the chat history helped participants reach a consensus. We present implications for the design of chatbots for collaborative settings