Operation and performance of the Ciba-Corning 512 coagulation monitor during parabolic flight

The goal was to assess the functionality and evaluate the procedures and operations required to operate the Ciba-Corning 512 Coagulation Monitor during parabolic flight. This monitor determines the clotting characteristics of blood. The analyzer operates by laser detection of the cessation of blood flow in a capillary channel within a test cartridge. Test simulator results were excellent for both pre-and post-flight. In-flight results were not obtained due to the warm-up time required for the simulator. Since this is an electronic function only, the expected results on the simulator would be the same in zero-g

Ontogenetic Survey of Histone Modifications in an Annelid

Histone modifications are widely recognized for their fundamental importance in regulating gene expression in embryonic development in a wide range of eukaryotes, but they have received relatively little attention in the development of marine invertebrates. We surveyed histone modifications throughout the development of a marine annelid, Polydora cornuta, to determine if modifications could be detected immunohistochemically and if there were characteristic changes in modifications throughout ontogeny (surveyed at representative stages from oocyte to adult). We found a common time of onset for three histone modifications in early cleavage (H3K14ac, H3K9me, and H3K4me2), some differences in the distribution of modifications among germ layers, differences in epifluorescence intensity in specific cell lineages suggesting that hyperacetylation (H3K14ac) and hypermethylation (H3K9me) occur during differentiation, and an overall decrease in the distribution of modifications from larvae to adults. Although preliminary, these results suggest that histone modifications are involved in activating early development and differentiation in a marine invertebrate

Treatment switching in cancer trials: Issues and proposals

Objectives: Treatment switching occurs when patients in a randomized clinical trial switch from the treatment initially assigned to them to another treatment, typically from the control to experimental treatment. This study discusses the issues this raises and possible approaches to addressing them in trials of cancer drugs. Methods: Stakeholders from around the world were invited to a 1.5-day Workshop in Adelaide, Australia. This study attempts to capture the key points from the discussion and the perspectives of the various stakeholder groups, but is not a formal consensus statement. Results: Treatment switching raises challenging ethical issues with arguments for and against allowing it. It is increasingly common in cancer drug trials and presents challenges for the interpretation of results by regulators, clinicians, patients, and payers. Proposals are offered for good practice in the design, management, and analysis of trials and wider development programs for cancer drugs in which treatment switching has occurred or is likely to. Recommendations are also offered for further action to improve understanding of the importance and challenges of treatment switching and to promote agreement between key stakeholders on guidelines and other steps to address these challenges. Conclusions: The handling of treatment switching in trials is of concern to all stakeholders. On the basis of the discussions at the Adelaide International Workshop, there would appear to be common ground on approaches to addressing treatment switching in cancer trials and scope for the development of formal guidelines to inform the work of regulators, payers, industry, trial designers and other stakeholders

Apelin receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The apelin receptor (nomenclature as agreed by the NC-IUPHAR Subcommittee on the apelin receptor [68]) responds to apelin, a 36 amino-acid peptide derived initially from bovine stomach. apelin-36, apelin-13 and [Pyr1]apelin-13 are the predominant endogenous ligands which are cleaved from a 77 amino-acid precursor peptide (APLN, Q9ULZ1) by a so far unidentified enzymatic pathway [80]. A second family of peptides discovered independently and named Elabela [11] or Toddler, that has little sequence similarity to apelin, is present, and functional at the apelin receptor in the adult cardiovascular system [87, 67]. Structure-activity relationship Elabela analogues have been described [61]

Apelin receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The apelin receptor (nomenclature as agreed by the NC-IUPHAR Subcommittee on the apelin receptor [68]) responds to apelin, a 36 amino-acid peptide derived initially from bovine stomach. apelin-36, apelin-13 and [Pyr1]apelin-13 are the predominant endogenous ligands which are cleaved from a 77 amino-acid precursor peptide (APLN, Q9ULZ1) by a so far unidentified enzymatic pathway [80]. A second family of peptides discovered independently and named Elabela [11] or Toddler, that has little sequence similarity to apelin, is present, and functional at the apelin receptor in the adult cardiovascular system [87, 67]. Structure-activity relationship Elabela analogues have been described [61]

Dysmorphism of urinary red blood cells—Value in diagnosis

Dysmorphism of urinary red blood cells—Value in diagnosis. To aid investigation into the clinical problem of hematuria, assessment of abnormalities in the shape of red cells in the urine (dysmorphism) is gaining popularity in nephrology. However, there is uncertainty in the literature regarding both the number of red blood cells (RBC) in normal urine, as well as the quantification of dysmorphism. We have shown that in normal urine (N = 27) the number of RBC is less than 2,000/ml as assessed by scanning electron microscopy of filtered urine specimens from normal volunteers without known renal disease, which compared to less than 1,000/ml by centrifugation and phase contrast microscopy of the same specimen. To determine whether dysmorphism of urinary red blood cells was a significant predictor of glomerular disease we compared the number of dysmorphic cells in the urine of patients with biopsy proven glomerulonephritis (GN), before and immediately after renal biopsy. We also compared the number of dysmorphic cells in patients with glomerulonephritis to those with lower urinary tract bleeding. Renal biopsy caused significant dysmorhpic hematuria, indicating that dysmorphism suggests renal rather than glomerular bleeding. Although patients with GN had significantly more dysmorphic urinary RBC when compared to those with lower tract urinary bleeding, the overlap was such that one could only be confident of renal hematuria if they accounted for greater than 75% of the total number of RBC. Non renal hematuria is present if number of dysmorphic cells is less than 17% of total RBC. Thus dysmorphism of urinary RBC is a useful diagnostic tool, but only if strict criteria established for each laboratory are adhered to

The evolutionary origin of avian facial bristles and the likely role of rictal bristles in feeding ecology

Facial bristles are one of the least described feather types and have not yet been systematically studied across phylogenetically diverse avian species. Consequently, little is known about their form, function and evolutionary history. Here we address this knowledge gap by characterising the evolution of facial bristles for the first time. We especially focus on rictal bristle presence and their associations with foraging behaviour, diet and habitat preferences in 1022 avian species, representing 91 families in 29 orders. Results reveal that upper rictal, lower rictal and interramal bristles were likely to be present in the most recent common ancestor of this avian phylogeny, whereas narial bristles were likely to be absent. Rictal bristle presence, length and shape varied both within and between avian orders, families and genera. Rictal bristles were gained or lost multiple times throughout evolution, which suggest that the different morphologies observed within species might not be homologous. Phylogenetic relatedness is also not likely to be the only driver of rictal bristle presence and morphology. Rictal bristle presence and length were associated with species-specific ecological traits, especially nocturnality. Our findings suggest that species foraging in low-light conditions are likely to have longer rictal bristles, and that rictal bristles are likely to have evolved in early birds

Effects of improved home heating on asthma in community dwelling children: randomised controlled trial

Objective To assess whether non-polluting, more effective home heating (heat pump, wood pellet burner, flued gas) has a positive effect on the health of children with asthma