Clinical characteristics and sequelae of intrapartum hypertension : a retrospective cohort study

Background: In a significant proportion of pregnant women, elevated blood pressure may first present during the intrapartum period. This phenomenon, intrapartum hypertension, is often overlooked as blood pressure during delivery is attributed to labour pain, analgesic agents and haemodynamic changes. Thus the true prevalence and clinical significance of intrapartum hypertension remains unknown. This study sought to define the prevalence of intrapartum hypertension in previously normotensive women, identify associated clinical characteristics, and its impact on maternal and fetal outcomes. Methods: In this single-center retrospective cohort study, all available partograms were reviewed over a 1-month period at an outer metropolitan hospital in Sydney (Campbelltown Hospital). Women with diagnosed hypertensive disorders of pregnancy during the incident pregnancy were excluded. A total of 229 deliveries were included in the final analysis. Intrapatum hypertension (IH) was defined as two or more systolic blood pressure (SBP)⩾140 mmHg or diastolic blood pressure (DBP)⩾90 mmHg during the intrapartum. Demographic data at the time of the first antenatal visit for the incident pregnancy as well as final maternal outcomes (intrapartum and post-partum) and fetal outcomes were collected. Statistical analyses were carried out using SPSSv27 with adjustments for baseline variables. Results: Amongst 229 deliveries, 32 women (14%) had intrapartum hypertension. Older maternal age (p = 0.02), higher body mass index (p < 0.01) and higher diastolic blood pressure at the first antenatal visit (p = 0.03) were associated with intrapartum hypertension. A longer second stage of labour (p = 0.03), intrapartum non-steroidal anti-inflammatory medications (p < 0.01) and epidural anaesthesia (p = 0.03) were associated with intrapartum hypertension, while IV syntocin for labour induction was not. Women with intrapartum hypertension had a longer inpatient admission following delivery (p < 0.01), and elevated postpartum BP (p = 0.02) with discharge on antihypertensive medications (p < 0.01). Intrapartum hypertension was not associated with poor fetal outcomes, though subgroup analyses showed that women who had at least a single elevated blood pressure reading during the intrapartum experienced poorer fetal outcomes. Conclusion: In previously normotensive women, 14% developed intrapartum hypertension during delivery. This was associated with postpartum hypertension, longer maternal admission and discharge with antihypertensive medications. There was no difference in fetal outcomes

Biotechnologies as catalysts for driving net zero

R&amp;D impact delivered by this work extends to policy development and to the benefits derived from delivering circularity, green growth and reducing carbon emissions by anaerobic digestion that (1) recovers a variety of organic wastes and low value biomass and (2) produces bioenergy and fertiliser. Other biotechnologies being developed can recover resources for the production of fuels (CH4, H2 and NH3), chemicals e.g. volatile fatty acids, biopolymers e.g. polyhydroxyalkanoates and single-cell proteins that can be used for animal feed. Biotechnologies delivering solutions for Power to X, for energy storage and for the capture and use of carbon have also been a focus of our research. Monitoring and control methodologies for the biotechnologies have been developed, including the use of analytical technologies such as FTNIR, GC-IMS and qPCR. Work continues on the valorisation of digestates as microbial and algae growth media, and the recovery of nutrients (NPK). Evaluations of the fate of polymers in the environment, their biochemical recycling and the production of biostimulants for soil and crop improvements, nitrogen fixing and emissions’ reduction are all in progress. Technologies are currently across the TRL 3-6 range and require further R&amp;D to progress them to commercialisation. Deploying industrial biotechnologies is essential to act as sustainable catalysts for change and for delivering net zero, circular economy and green growth. Biotechnologies can impact beneficially on the sustainability of cities and benefit their relationship and integration with surrounding rural areas

Toxigenic Clostridium difficile colonization among hospitalised adults; risk factors and impact on survival

Objectives: To establish risk factors for Clostridium difficile colonization among hospitalized patients in England. Methods: Patients admitted to elderly medicine wards at three acute hospitals in England were recruited to a prospective observational study. Participants were asked to provide a stool sample as soon as possible after enrolment and then weekly during their hospital stay. Samples were cultured for C. difficile before ribotyping and toxin detection by PCR. A multivariable logistic regression model of risk factors for C. difficile colonization was fitted from univariable risk factors significant at the p < 0.05 level. Results: 410/727 participants submitted ≥1 stool sample and 40 (9.8%) carried toxigenic C. difficile in the first sample taken. Ribotype 106 was identified three times and seven other ribotypes twice. No ribotype 027 strains were identified. Independent predictors of colonization were previous C. difficile infection (OR 4.53 (95% C.I. 1.33–15.48) and malnutrition (MUST score ≥2) (OR 3.29 (95% C.I. 1.47–7.35)). Although C. difficile colonised patients experienced higher 90-day mortality, colonization was not an independent risk for death. Conclusions: In a non-epidemic setting patients who have previously had CDI and have a MUST score of ≥2 are at increased risk of C. difficile colonization and could be targeted for active surveillance to prevent C. difficile transmission

A Validated Composite Organ and Hematologic Response Model for Early Assessment of Treatment Outcomes in Light Chain Amyloidosis

Newly diagnosed AL amyloidosis patients were evaluated to develop a model for early assessment of treatment benefit at 6 months, integrating both hematologic (HR) and organ response (OR) assessment (testing cohort, Mayo: n = 473; validation cohort, Pavia: n = 575). Multiple OR were assessed as follows: All OR (AOR): response in all organs, mixed OR (MOR): response in some organs, no OR (NOR)]. AOR rates at 6 months improved with deepening HR; complete response (CR; 38%, 35%), very good partial response (VGPR; 30%, 26%), and partial response (PR; 16%, 21%), respectively. A composite HR/OR (CHOR) model was developed using incremental scoring based on hazard ratios with scores of 0-3 for HR (0-CR, 1-VGPR, 2-PR, 3-no response) and 0-2 for OR (0-AOR, 1-MOR, 2-NOR). Patients could be divided into two distinct CHOR groups (scores 0-3 and 4-5), with median OS in group 1 and group 2: Not reached vs. 34 months, p \u3c 0.001 [Mayo] and 87 vs. 23 months, p \u3c 0.001 [Pavia]. In conclusion, we developed a model that can assess multiple organs concurrently, and integrate both HR and OR assessments to determine early clinical benefit with treatment, which may be used as a surrogate end-point in trials and to compare outcomes with different therapies

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis

Immunoglobulin light-chain (AL) amyloidosis is a rare, incurable plasma cell disorder. Its therapy has benefited immensely from the expanding drug armamentarium available for multiple myeloma. Pomalidomide in combination with weekly dexamethasone (Pom/dex) is active among patients with relapsed myeloma. In the present study, we explored the Pom/dex combination in patients with previously treated AL. Patients were eligible for this prospective phase 2 trial if they had had at least one prior regimen and if they had reasonably preserved organ function. Patients were treated with oral Pom/dex. Thirty-three patients were enrolled. The median age was 66 years. Median time from diagnosis to on-study was 37 months. Eighty-two percent had cardiac involvement. The confirmed hematologic response rate was 48%, with a median time to response of 1.9 months. Organ improvement was documented in 5 patients. The median overall and progression-free survival rates were 28 and 14 months, respectively; the 1-year overall and progression-free survival rates were 76% and 59%, respectively. There was a discordance between the hematologic response and the N-terminal probrain natriuretic peptide response. The most common grade 3-5 adverse events, regardless of attribution, were neutropenia and fatigue. We conclude that pomalidomide appears to be a valuable drug covering an unmet clinical need in patients with previously treated AL. The trial is registered at www.clinicaltrials.gov as NCT00558896. (Blood. 2012;119(23): 5397-5404

A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci

Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma (MM)

An expanded evaluation of protein function prediction methods shows an improvement in accuracy

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent. Keywords: Protein function prediction, Disease gene prioritizationpublishedVersio

An Expanded Evaluation of Protein Function Prediction Methods Shows an Improvement In Accuracy

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent