Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.
To bring together a large ...multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.
A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference.
Online Delphi survey and consensus conference.
The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.
Statements were ranked by experts according to their level of agreement: 1–3 (disagree), 4–6 (equivocal), 7–9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).
Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease.
These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.
Aims: To determine whether the risk of hyponatraemia in children with gastroenteritis receiving intravenous (IV) fluids is decreased by the use of 0.9% saline. Methods: A prospective randomised study ...was carried out in a tertiary paediatric hospital. A total of 102 children with gastroenteritis were randomised to receive either 0.9% saline + 2.5% dextrose (NS) or 0.45% saline + 2.5% dextrose (N/2) at a rate determined by their treating physician according to hospital guidelines and clinical judgement. Plasma electrolytes, osmolality, and plasma glucose were measured before (T0) and 4 hours after (T4) starting IV fluids, and subsequently if clinically indicated. Electrolytes and osmolality were measured in urine samples. Results were analysed according to whether children were hyponatraemic (plasma sodium <135 mmol/l) or normonatraemic at T0. Results: At T0, mean (SD) plasma sodium was 135 (3.3) mmol/l (range 124–142), with 37/102 (36%) hyponatraemic. At T4, mean plasma sodium in children receiving N/2 remained unchanged in those initially hyponatraemic (n = 16), but fell 2.3 (2.2) mmol/l in the normonatraemic group. In contrast, among children receiving NS, mean plasma sodium was 2.4 (2.0) mmol/l higher in those hyponatraemic at baseline (n = 21) and unchanged in the initially normonatraemic children. In 16 children who were still receiving IV fluids at 24 hours, 3/8 receiving N/2 were hyponatraemic compared with 0/8 receiving NS. No child became hypernatraemic. Conclusions: In gastroenteritis treated with intravenous fluids, normal saline is preferable to hypotonic saline because it protects against hyponatraemia without causing hypernatraemia.
Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by impaired color discrimination, low visual acuity, photosensitivity, and nystagmus. To date, six genes have been ...associated with ACHM (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6), the majority of these being implicated in the cone phototransduction cascade. CNGA3 encodes the CNGA3 subunit of the cyclic nucleotide‐gated ion channel in cone photoreceptors and is one of the major disease‐associated genes for ACHM. Herein, we provide a comprehensive overview of the CNGA3 variant spectrum in a cohort of 1060 genetically confirmed ACHM patients, 385 (36.3%) of these carrying “likely disease‐causing” variants in CNGA3. Compiling our own genetic data with those reported in the literature and in public databases, we further extend the CNGA3 variant spectrum to a total of 316 variants, 244 of which we interpreted as “likely disease‐causing” according to ACMG/AMP criteria. We report 48 novel “likely disease‐causing” variants, 24 of which are missense substitutions underlining the predominant role of this mutation class in the CNGA3 variant spectrum. In addition, we provide extensive in silico analyses and summarize reported functional data of previously analyzed missense, nonsense and splicing variants to further advance the pathogenicity assessment of the identified variants.
Comprehensive overview of the CNGA3 variant spectrum extending it to 316 variants.
We examine the UV reprocessing efficiencies of warm dust and polycyclic aromatic hydrocarbons (PAHs) through an analysis of the mid- and far-infrared surface luminosity densities of 85 nearby ...Hα-selected star-forming galaxies detected by the volume-limited KPNO (Kitt Peak National Observatory) International Spectroscopic Survey (KISS). Because Hα selection is not biased towards continuum-bright objects, the KISS sample spans a wide range in stellar masses (108–1012 M⊙), as well as Hα luminosity (1039–1043 erg s−1), mid-infrared 8.0 μm luminosity (1041–1044 erg s−1), and Bw − R colour (−0.1–2.2). We find that mid-infrared PAH emission in the Spitzer InfraRed Array Camera (IRAC) 8.0 μm band correlates with star formation, and that the efficiency with which galaxies reprocess UV energy into PAH emission depends on metallicity. We also find that the relationship between far-infrared luminosity in the Spitzer Multiband Imaging Photometer for Spitzer 24 μm band pass and Hα-measured star formation rate varies from galaxy to galaxy within our sample; we do not observe a metallicity dependence in this relationship. We use optical colours and established mass-to-light relationships to determine stellar masses for the KISS galaxies; we compare these masses to those of nearby galaxies as a confirmation that the volume-limited nature of KISS avoids strong biases. We also examine the relationship between IRAC 3.6 μm luminosity and galaxy stellar mass, and find a colour-dependent correlation between the two.
The Arecibo Galaxy Environment Survey (AGES) is one of several H i surveys utilizing the new Arecibo L-band Feed Array (ALFA) fitted to the 305-m radio telescope at Arecibo. The survey is ...specifically designed to investigate various galactic environments to higher sensitivity, higher velocity resolution and higher spatial resolution than previous fully sampled, 21-cm multibeam surveys. The emphasis is on making detailed observations of nearby objects although the large system bandwidth (100 MHz) will allow us to quantify the H i properties over a large instantaneous velocity range. In this paper, we describe the survey and its goals and present the results from the precursor observations of a 5 × 1-deg2 region containing the nearby (∼10 Mpc) NGC 628 group. We have detected all the group galaxies in the region including the low-mass (MH I∼107 M⊙) dwarf, dw0137+1541. The fluxes and velocities for these galaxies compare well with previously published data. There is no intragroup neutral gas detected down to a limiting column density of 2 × 1018 cm−2. In addition to the group galaxies we have detected 22 galaxies beyond the NGC 628 group, nine of which are previously uncatalogued. We present the H i data for these objects and also SuperCOSMOS images for possible optical galaxies that might be associated with the H i signal. We have used V/Vmax analysis to model how many galaxies beyond 1000 km s−1 should be detected and compare this with our results. The predicted number of detectable galaxies varies depending on the H i mass function (HIMF) used in the analysis. Unfortunately the precursor survey area is too small to determine whether this is saying anything fundamental about the HIMF or simply highlighting the effect of low number statistics. This is just one of many questions that will be addressed by the complete AGES survey.
Summary
Background
Eosinophils in the nasal mucosa are an elemental feature of allergic rhinitis.
Objective
Our objective was to explore eosinophilic inflammation and its impact on respiratory virus ...infection at the nasal mucosa.
Methods
Inflammation in the nasal mucosae of mice was evaluated in response to repetitive stimulation with strict intranasal volumes of a filtrate of Alternaria alternata. Mice were then challenged with influenza virus.
Results
Repetitive stimulation with A. alternata resulted in eosinophil recruitment to the nasal passages in association with elevated levels of IL‐5, IL‐13 and eotaxin‐1; eosinophil recruitment was diminished in eotaxin‐1−/− mice, and abolished in Rag1−/− mice. A. alternata also resulted in elevated levels of nasal wash IgA in both wild‐type and eosinophil‐deficient ∆dblGATA mice. Interestingly, A. alternata‐treated mice responded to an influenza virus infection with profound weight loss and mortality compared to mice that received diluent alone (0% vs 100% survival, ***P < .001); the lethal response was blunted when A. alternata was heat‐inactivated. Minimal differences in virus titre were detected, and eosinophils present in the nasal passages at the time of virus inoculation provided no protection against the lethal sequelae. Interestingly, nasal wash fluids from mice treated with A. alternata included more neutrophils and higher levels of pro‐inflammatory mediators in response to virus challenge, among these, IL‐6, a biomarker for disease severity in human influenza.
Conclusions and Clinical Relevance
Repetitive administration of A. alternata resulted in inflammation of the nasal mucosae and unanticipated morbidity and mortality in response to subsequent challenge with influenza virus. Interestingly, and in contrast to findings in the lower airways, eosinophils recruited to the nasal passages provided no protection against lethal infection. As increased susceptibility to influenza virus among individuals with rhinitis has been the subject of several clinical reports, this model may be used for further exploration of these observations.
Giardia duodenalis is the most common intestinal parasite of humans in the USA, but the risk factors for sporadic (non-outbreak) giardiasis are not well described. The Centers for Disease Control and ...Prevention and the Colorado and Minnesota public health departments conducted a case-control study to assess risk factors for sporadic giardiasis in the USA. Cases (N = 199) were patients with non-outbreak-associated laboratory-confirmed Giardia infection in Colorado and Minnesota, and controls (N = 381) were matched by age and site. Identified risk factors included international travel (aOR = 13.9; 95% CI 4.9–39.8), drinking water from a river, lake, stream, or spring (aOR = 6.5; 95% CI 2.0–20.6), swimming in a natural body of water (aOR = 3.3; 95% CI 1.5–7.0), male–male sexual behaviour (aOR = 45.7; 95% CI 5.8–362.0), having contact with children in diapers (aOR = 1.6; 95% CI 1.01–2.6), taking antibiotics (aOR = 2.5; 95% CI 1.2–5.0) and having a chronic gastrointestinal condition (aOR = 1.8; 95% CI 1.1–3.0). Eating raw produce was inversely associated with infection (aOR = 0.2; 95% CI 0.1–0.7). Our results highlight the diversity of risk factors for sporadic giardiasis and the importance of non-international-travel-associated risk factors, particularly those involving person-to-person transmission. Prevention measures should focus on reducing risks associated with diaper handling, sexual contact, swimming in untreated water, and drinking untreated water.
We have determined the complete sequence of the mitochondrial genome of the scaphopod mollusk Graptacme eborea (14,492 nts) and completed the sequence of the mitochondrial genome of the bivalve ...mollusk Mytilus edulis (16,740 nts). (The name Graptacme eborea is a revision of the species formerly known as Dentalium eboreum.) G. eborea mtDNA contains the 37 genes that are typically found and has the genes divided about evenly between the two strands, but M. edulis contains an extra trnM and is missing atp8, and it has all genes on the same strand. Each has a highly rearranged gene order relative to each other and to all other studied mtDNAs. G. eborea mtDNA has almost no strand skew, but the coding strand of M. edulis mtDNA is very rich in G and T. This is reflected in differential codon usage patterns and even in amino acid compositions. G. eborea mtDNA has fewer noncoding nucleotides than any other mtDNA studied to date, with the largest noncoding region only 24 nt long. Phylogenetic analysis using 2,420 aligned amino acid positions of concatenated proteins weakly supports an association of the scaphopod with gastropods to the exclusion of Bivalvia, Cephalopoda, and Polyplacophora, but it is generally unable to convincingly resolve the relationships among major groups of the Lophotrochozoa, in contrast to the good resolution seen for several other major metazoan groups.
Corneal wound healing is impaired in diabetic cornea. The purpose of this study was to examine patients with type 1 diabetes mellitus for changes in corneal morphology and to correlate corneal ...sensitivity, subbasal nerve morphology, and degree of polyneuropathy with each other.
Forty-four eyes of 23 patients with diabetes and nine control eyes were included. Corneal sensitivity was tested with a Cochet-Bonnet esthesiometer (Luneau, Paris, France), and corneal morphology and epithelial and corneal thickness were determined by in vivo confocal microscopy. The density of subbasal nerves was evaluated by calculating the number of long subbasal nerve fiber bundles per confocal microscopic field. The degree of polyneuropathy was evaluated using the clinical part of the Michigan Neuropathy Screening Instrument (MNSI) classification, and retinopathy was evaluated using fundus photographs.
A reduction of long nerve fiber bundles per image was noted to have occurred already in patients with mild to moderate neuropathy, but corneal mechanical sensitivity was reduced only in patients with severe neuropathy. Compared with control subjects the corneal thickness was increased in patients with diabetes without neuropathy. The epithelium of patients with diabetes with severe neuropathy was significantly thinner than that of patients with diabetes without neuropathy.
Confocal microscopy appears to allow early detection of beginning neuropathy, because decreases in nerve fiber bundle counts precede impairment of corneal sensitivity. Apparently, the cornea becomes thicker in a relatively early stage of diabetes but does not further change with the degree of neuropathy. A reduction in neurotrophic stimuli in severe neuropathy may induce a thin epithelium that may lead to recurrent erosions.
PDF
