Albumin versus balanced crystalloid for resuscitation in the treatment of sepsis:A protocol for a randomised controlled feasibility study, “ABC-Sepsis”

BACKGROUND: Patients presenting with suspected sepsis to secondary care often require fluid resuscitation to correct hypovolaemia and/or septic shock. Existing evidence signals, but does not demonstrate, a benefit for regimes including albumin over balanced crystalloid alone. However, interventions may be started too late, missing a critical resuscitation window. METHODS: ABC Sepsis is a currently recruiting randomised controlled feasibility trial comparing 5% human albumin solution (HAS) with balanced crystalloid for fluid resuscitation in patients with suspected sepsis. This multicentre trial is recruiting adult patients within 12 hours of presentation to secondary care with suspected community acquired sepsis, with a National Early Warning Score ≥5, who require intravenous fluid resuscitation. Participants are randomised to 5% HAS or balanced crystalloid as the sole resuscitation fluid for the first 6 hours. OBJECTIVES: Primary objectives are feasibility of recruitment to the study and 30-day mortality between groups. Secondary objectives include in-hospital and 90-day mortality, adherence to trial protocol, quality of life measurement and secondary care costs. DISCUSSION: This trial aims to determine the feasibility of conducting a trial to address the current uncertainty around optimal fluid resuscitation of patients with suspected sepsis. Understanding the feasibility of delivering a definitive study will be dependent on how the study team are able to negotiate clinician choice, Emergency Department pressures and participant acceptability, as well as whether any clinical signal of benefit is detected

Methods to determine the interactions of micro- and nanoparticles with mucus

The present review provides an overview of methods and techniques for studying interactions of micro- and nanoparticulate drug delivery system with mucus. Nanocarriers trapped by mucus are featuring a change in particle size and zeta potential that can be utilized to predict their mucus permeation behavior. Furthermore, interactions between nanoparticulate drug delivery systems and mucus layer modify the viscoelasticity of mucus which can be detected via rheological studies and quartz crystal microbalance with dissipation monitoring (QCM-D) analysis. To have a closer look at molecular interactions between drug carrier and mucus small-angle neutron scattering (SANS) is an appropriate analysis technique. Moreover, different methods to determine particle diffusion in mucus such as the newly established Transwell diffusion system, rotating silicone tube technique, multiple-particle tracking (MPT) and diffusion NMR are summarized within this review. The explanations and discussed pros and cons of collated methods and techniques should provide a good starting point for all those looking forward to move in this interesting field

Tempo and Pattern of Avian Brain Size Evolution

Relative brain sizes in birds can rival those of primates, but large-scale patterns and drivers of avian brain evolution remain elusive. Here, we explore the evolution of the fundamental brain-body scaling relationship across the origin and evolution of birds. Using a comprehensive dataset sampling> 2,000 modern birds, fossil birds, and theropod dinosaurs, we infer patterns of brain-body co-variation in deep time. Our study confirms that no significant increase in relative brain size accompanied the trend toward miniaturization or evolution of flight during the theropod-bird transition. Critically, however, theropods and basal birds show weaker integration between brain size and body size, allowing for rapid changes in the brain-body relationship that set the stage for dramatic shifts in early crown birds. We infer that major shifts occurred rapidly in the aftermath of the Cretaceous-Paleogene mass extinction within Neoaves, in which multiple clades achieved higher relative brain sizes because of a reduction in body size. Parrots and corvids achieved the largest brains observed in birds via markedly different patterns. Parrots primarily reduced their body size, whereas corvids increased body and brain size simultaneously (with rates of brain size evolution outpacing rates of body size evolution). Collectively, these patterns suggest that an early adaptive radiation in brain size laid the foundation for subsequent selection and stabilization

DIY Methods 2022 Conference Proceedings

As the past years have proven, the methods for conducting and distributing research that we’ve inherited from our disciplinary traditions can be remarkably brittle in the face of rapidly changing social and mobility norms. The ways we work and the ways we meet are questions newly opened for practical and theoretical inquiry; we both need to solve real problems in our daily lives and account for the constitutive effects of these solutions on the character of the knowledge we produce. Methods are not neutral tools, and nor are they fixed ones. As such, the work of inventing, repairing, and hacking methods is a necessary, if often underexplored, part of the wider research process. This conference aims to better interrogate and celebrate such experiments with method. Borrowing from the spirit and circuits of exchange in earlier DIY cultures, it takes the form of a zine ring distributed via postal mail. Participants will craft zines describing methodological experiments and/or how-to guides, which the conference organisers will subsequently mail out to all participants. Feedback on conference proceedings will also proceed through the mail, as well as via an optional Twitter hashtag. The conference itself is thus an experiment with different temporalities and medialities of research exchange. As a practical benefit, this format guarantees that the experience will be free of Zoom fatigue, timezone difficulties, travel expenses, and visa headaches. More generatively, it may also afford slower thinking, richer aesthetic possibilities, more diverse forms of circulation, and perhaps even some amount of delight. The conference format itself is part of the DIY experiment

Meta-analyses of genome-wide association studies for postpartum depression

Objective: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD. Method: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)–based heritability (), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system. Results: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD. Conclusions: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone)

68Ga-prostate specific membrane antigen (PSMA) positron emission tomography (PET) for primary staging of high-risk prostate cancer: a systematic review

To systematically review currently available data on 68Ga-prostate specific membrane antigen (PSMA) positron emission tomography (PET) used for the primary staging of high-risk prostate cancer.We performed critical reviews of EMBASE, Web of Science (including MEDLINE) and Cochrane databases in October 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. We included studies that utilized 68Ga-PSMA PET for primary staging of prostate cancer. Quality was assessed using the Critical Appraisal Skills Programme checklist for diagnostic test studies.Following our systematic search strategy, 12 studies were included for assessment. These studies comprised a total of 322 patients who underwent 68Ga-PSMA PET scanning for the purpose of primary staging. Only 5 of these studies included histopathologic correlation data. High variation in methodology and outcomes such as sensitivity (range 33-99%) and specificity (>\ua090%) was seen across all studies. The ability of 68Ga-PSMA PET to detect malignant lesions was evident across studies, with most studies demonstrating increased detection rates with respect to conventional imaging modalities.In the primary staging of prostate cancer 68Ga-PSMA PET appears to outperform traditional imaging modalities. Overall, there are few high-quality studies investigating 68Ga-PSMA PET in this sub-group highlighting the need for formal assessment of PSMA PET in the form of large-volume, prospective studies

Importance of non-covalent interactions in a nitrile anion metal-complex based on pyridine ligands: A theoretical and experimental approach

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