The treatment of rest pain, ulceration, and gangrene of the leg (severe limb ischaemia) remains controversial. We instigated the BASIL trial to compare the outcome of bypass surgery and balloon ...angioplasty in such patients.
We randomly assigned 452 patients, who presented to 27 UK hospitals with severe limb ischaemia due to infra-inguinal disease, to receive a surgery-first (n=228) or an angioplasty-first (n=224) strategy. The primary endpoint was amputation (of trial leg) free survival. Analysis was by intention to treat. The BASIL trial is registered with the National Research Register (NRR) and as an International Standard Randomised Controlled Trial, number ISRCTN45398889.
The trial ran for 5·5 years, and follow-up finished when patients reached an endpoint (amputation of trial leg above the ankle or death). Seven individuals were lost to follow-up after randomisation (three assigned angioplasty, two surgery); of these, three were lost (one angioplasty, two surgery) during the first year of follow-up. 195 (86%) of 228 patients assigned to bypass surgery and 216 (96%) of 224 to balloon angioplasty underwent an attempt at their allocated intervention at a median (IQR) of 6 (3–16) and 6 (2–20) days after randomisation, respectively. At the end of follow-up, 248 (55%) patients were alive without amputation (of trial leg), 38 (8%) alive with amputation, 36 (8%) dead after amputation, and 130 (29%) dead without amputation. After 6 months, the two strategies did not differ significantly in amputation-free survival (48 vs 60 patients; unadjusted hazard ratio 1·07, 95% CI 0·72–1·6; adjusted hazard ratio 0·73, 0·49–1·07). We saw no difference in health-related quality of life between the two strategies, but for the first year the hospital costs associated with a surgery-first strategy were about one third higher than those with an angioplasty-first strategy.
In patients presenting with severe limb ischaemia due to infra-inguinal disease and who are suitable for surgery and angioplasty, a bypass-surgery-first and a balloon-angioplasty-first strategy are associated with broadly similar outcomes in terms of amputation-free survival, and in the short-term, surgery is more expensive than angioplasty.
The identification of immunogenic glycotopes that render glycoconjugate vaccines protective is key to improving vaccine efficacy. Synthetic oligosaccharides are an attractive alternative to ...the heterogeneous preparations of purified polysaccharides that most marketed glycoconjugate vaccines are based on. To investigate the potency of semi-synthetic glycoconjugates, we chose the least-efficient serotype in the current pneumococcal conjugate vaccine Prevnar 13, Streptococcus pneumoniae serotype 3 (ST3). Glycan arrays containing synthetic ST3 repeating unit oligosaccharides were used to screen a human reference serum for antibodies and to define the recognition site of two ST3-specific protective monoclonal antibodies. The glycan array screens identified a tetrasaccharide that was selected for in-depth immunological evaluation. The tetrasaccharide-CRM197 carrier protein conjugate elicited protective immunity as evidenced by opsonophagocytosis assays and protection against pneumonia caused by ST3 in mice. Formulation of the defined protective lead candidate glycotope has to be further evaluated to elicit optimal long-term immunity.
Display omitted
•Glycan arrays reveal epitopes of two monoclonal antibodies to S. pneumoniae 3 CPS•CRM197 conjugates of one identified tetrasaccharide antigen are immunogenic in mice•Vaccination with the glycoconjugates protects mice from pneumococcal pneumonia
Parameswarappa et al. describe a synthetic immunogenic tetrasaccharide hapten of the capsular polysaccharide of Streptococcus pneumoniae serotype 3. Glycoconjugates of this antigen are able to protect mice from pneumococcal pneumonia in a lethal transnasal challenge model.
Abstract
Objective
Biomechanics represents the common final output through which all biopsychosocial constructs of back pain must pass, making it a rich target for phenotyping. To exploit this ...feature, several sites within the NIH Back Pain Consortium (BACPAC) have developed biomechanics measurement and phenotyping tools. The overall aims of this article were to: 1) provide a narrative review of biomechanics as a phenotyping tool; 2) describe the diverse array of tools and outcome measures that exist within BACPAC; and 3) highlight how leveraging these technologies with the other data collected within BACPAC could elucidate the relationship between biomechanics and other metrics used to characterize low back pain (LBP).
Methods
The narrative review highlights how biomechanical outcomes can discriminate between those with and without LBP, as well as among levels of severity of LBP. It also addresses how biomechanical outcomes track with functional improvements in LBP. Additionally, we present the clinical use case for biomechanical outcome measures that can be met via emerging technologies.
Results
To answer the need for measuring biomechanical performance, our “Results” section describes the spectrum of technologies that have been developed and are being used within BACPAC.
Conclusion and Future Directions
The outcome measures collected by these technologies will be an integral part of longitudinal and cross-sectional studies conducted in BACPAC. Linking these measures with other biopsychosocial data collected within BACPAC increases our potential to use biomechanics as a tool for understanding the mechanisms of LBP, phenotyping unique LBP subgroups, and matching these individuals with an appropriate treatment paradigm.
Aim: The alpine region of mainland Australia is one of the world's 187 biodiversity hotspots. Genetic analyses of Australian alpine fauna indicate high levels of endemism on fine spatial scales, ...unlike Northern Hemisphere alpine systems where shallow genetic differentiation is typically observed among populations. These discrepancies have been attributed to differences in elevation and influence from glacial activity, and point to a unique phylogeographic history affecting Australian alpine biodiversity. To test generality of these findings across Australian alpine biota, we assessed patterns of genetic structure across plant species. Location: The Australian Alps, Victoria, eastern Australia. Methods: We used an economical pooled genotyping-by-sequencing (GBS) approach to examine patterns of genetic diversity among seven widespread species including shrubs and forbs from 16 mountain summits in the Australian Alpine National Park. Patterns of genetic structure among summit populations for each species were inferred from an average of 2,778 independent SNP loci using Bayesian phylogenomic inference and clustering approaches. Results: SNP results were consistent across species in identifying deep evolutionary splits among summit communities from the Northern and Central Victorian Alpine regions. These patterns of genetic structure are also consistent with those previously reported for invertebrate and mammal taxa. However, local genetic structure was less pronounced in the plants, supporting the notion that population connectivity tends to be higher in plant species. Main conclusion: There is deep lineage diversification between the North and Central Victorian Alpine regions, reflecting a high level of endemism. These findings differ from those reported for alpine biodiversity from New South Wales and much of the Northern Hemisphere, and support the notion that genetic diversity is typically greatest in areas least affected by historical ice sheet formation. We discuss the implications of our findings in the context of conservation planning, and highlight the benefits of this rapid and cost-effective genome scan approach for characterizing evolutionary processes at multispecies and landscape scales.
Abstract
Background
Women with a cervicovaginal microbiota dominated by
Lactobacillus
spp. are at reduced risk of acquiring sexually transmitted infections including HIV, but the biological ...mechanisms involved remain poorly defined. Here, we performed metaproteomics on vaginal swab samples from young South African women (
n
= 113) and transcriptomics analysis of cervicovaginal epithelial cell cultures to examine the ability of lactic acid, a metabolite produced by cervicovaginal lactobacilli, to modulate genital epithelial barrier function.
Results
Compared to women with
Lactobacillus
-depleted microbiota, women dominated by vaginal lactobacilli exhibit higher abundance of bacterial lactate dehydrogenase, a key enzyme responsible for lactic acid production, which is independently associated with an increased abundance of epithelial barrier proteins. Physiological concentrations of lactic acid enhance epithelial cell culture barrier integrity and increase intercellular junctional molecule expression.
Conclusions
These findings reveal a novel ability of vaginal lactic acid to enhance genital epithelial barrier integrity that may help prevent invasion by sexually transmitted pathogens.
IntroductionSurgical site infections following caesarean section are associated with significant morbidity. Vaginal preparation is the cleansing of the vaginal epithelium with an antibacterial ...solution to reduce the bacterial load and therefore reduce ascending genital tract infection. It is recommended by the WHO and a Cochrane review in 2018 concluded that vaginal preparation immediately before caesarean section probably reduces the rates of postoperative endometritis.ObjectiveTo implement vaginal preparation prior to caesarean section at Guy’s and St Thomas’ Hospital NHS Foundation Trust and reduce rates of deep surgical site infections.MethodsThe protocol (included within the appendices) for vaginal preparation prior to caesarean section was developed after reviewing the available evidence. Two vaginal preparation champions, a midwife and a scrub nurse, were selected to help promote and assist in the implementation. The first implementation cycle included elective and category II and III caesarean sections. To ensure acceptability, 20 women were asked to complete a questionnaire following vaginal preparation. Once the intervention was being performed in >85% of eligible women, the inclusion criteria was expanded to include category I caesarean sections.ResultsTwelve months following implementation, vaginal preparation was still being performed in 89% of eligible women. The deep surgical site infection rate is now the lowest recorded in the last 6 years. Vaginal preparation prior to caesarean section was acceptable to pregnant women and no adverse effects were reported.ConclusionsVaginal preparation prior to caesarean section has been successfully implemented at Guy’s and St Thomas’ Hospital NHS Foundation Trust. This simple, cheap intervention, performed with readily available materials, is still being performed in a high number of caesarean sections 12 months post-implementation. It has resulted in a reduction in deep surgical site infections. Involvement of key stakeholders and the recruitment of vaginal preparation champions were key to success.
Summary
Objective
In the absence of specific metabolic disorders, accurate predictors of response to ketogenic dietary therapies (KDTs) for treating epilepsy are largely unknown. We hypothesized that ...specific biochemical parameters would be associated with the effectiveness of KDT in humans with epilepsy. The parameters tested were β‐hydroxybutyrate, acetoacetate, nonesterified fatty acids, free and acylcarnitine profile, glucose, and glucose‐ketone index (GKI).
Methods
Biochemical results from routine blood tests conducted at baseline prior to initiation of KDT and at 3‐month follow‐up were obtained from 13 adults and 215 children with KDT response data from participating centers. One hundred thirty‐two (57%) of 228 participants had some data at both baseline and 3 months; 52 (23%) of 228 had data only at baseline; 22 (10%) of 228 had data only at 3 months; and 22 (10%) of 228 had no data. KDT response was defined as ≥50% seizure reduction at 3‐month follow‐up.
Results
Acetyl carnitine at baseline was significantly higher in responders (p < 0.007). It was not associated with response at 3‐month follow‐up. There was a trend for higher levels of free carnitine and other acylcarnitine esters at baseline and at 3‐month follow‐up in KDT responders. There was also a trend for greater differences in levels of propionyl carnitine and in β‐hydroxybutyrate measured at baseline and 3‐month follow‐up in KDT responders. No other biochemical parameters were associated with response at any time point.
Significance
Our finding that certain carnitine fractions, in particular baseline acetyl carnitine, are positively associated with greater efficacy of KDT is consistent with the theory that alterations in energy metabolism may play a role in the mechanisms of action of KDT.
The NASA Aerosol Cloud meTeorology Interactions oVer the western ATlantic Experiment (ACTIVATE) produced a unique dataset for research into aerosol–cloud–meteorology interactions, with applications ...extending from process-based studies to multi-scale model intercomparison and improvement as well as to remote-sensing algorithm assessments and advancements. ACTIVATE used two NASA Langley Research Center aircraft, a HU-25 Falcon and King Air, to conduct systematic and spatially coordinated flights over the northwest Atlantic Ocean, resulting in 162 joint flights and 17 other single-aircraft flights between 2020 and 2022 across all seasons. Data cover 574 and 592 cumulative flights hours for the HU-25 Falcon and King Air, respectively. The HU-25 Falcon conducted profiling at different level legs below, in, and just above boundary layer clouds (< 3 km) and obtained in situ measurements of trace gases, aerosol particles, clouds, and atmospheric state parameters. Under cloud-free conditions, the HU-25 Falcon similarly conducted profiling at different level legs within and immediately above the boundary layer. The King Air (the high-flying aircraft) flew at approximately ∼ 9 km and conducted remote sensing with a lidar and polarimeter while also launching dropsondes (785 in total). Collectively, simultaneous data from both aircraft help to characterize the same vertical column of the atmosphere. In addition to individual instrument files, data from the HU-25 Falcon aircraft are combined into “merge files” on the publicly available data archive that are created at different time resolutions of interest (e.g., 1, 5, 10, 15, 30, 60 s, or matching an individual data product's start and stop times). This paper describes the ACTIVATE flight strategy, instrument and complementary dataset products, data access and usage details, and data application notes. The data are publicly accessible through https://doi.org/10.5067/SUBORBITAL/ACTIVATE/DATA001 (ACTIVATE Science Team, 2020).
This study examined the experiences of four clinicians learning emotionally focused couple therapy (EFT). Two group interviews, separated by 6 years, explored topics that included emotion, gender, ...model differences, personal practitioner impact, and the long-term influence of EFT training on clinical work. Emotion emerged as a major theme, with three subthemes at each phase. Phase 1 results indicated an increase in personal awareness of emotions, a positive impact on close personal relationships, and challenges for males in learning to elicit and use emotion. Phase 2 results, 6 years later, revealed that focusing on emotions remained salient and that EFT continues to influence the work of each clinician to varying degrees. Limitations, future research suggestions, and clinical implications are discussed.
PDF
