Optimal Management of Adverse Events From Copanlisib in the Treatment of Patients With Non-Hodgkin Lymphomas

INTRODUCTION: Copanlisib is a phosphoinositol 3-kinase (PI3K) inhibitor approved for the third-line treatment of follicular non-Hodgkin lymphoma. Although the drug is generally well-tolerated, it can be associated with several unique and potentially serious adverse effects (AEs). Two of the most common toxicities not seen with other PI3K inhibitors include hyperglycemia and hypertension, which primarily occur during infusion and resolve shortly thereafter, and likely relate to targeting the PI3K alpha isoform. Other toxicities less commonly observed with copanlisib than with other approved drugs in this class include non-infectious pneumonitis, infections, diarrhea and colitis, and hepatobiliary toxicity. MATERIALS AND METHODS: A panel composed of experts in lymphoma, diabetes, and hypertension convened to develop guidance pertaining to the administration of copanlisib and the management of the AEs associated with copanlisib treatment. RESULTS: Recommendations were formulated pertaining to the management of AEs associated with copanlisib treatment, particularly infusion-related hyperglycemia and hypertension, noninfectious pneumonitis, infections, diarrhea, and colitis. The recommendations herein reflect the consensus of the members of this panel, all of whom contributed to these suggested approaches to patient supportive care. CONCLUSION: There are a number of challenges associated with the use of copanlisib. Infusion-related hypertension and hyperglycemia occur frequently, although they are transient, reversible, and rarely of clinical significance; this report provides guidance as to their management

The (A)gamma-195 (C -> G) mutation in hereditary persistence of fetal hemoglobin is not associated with activation of a reporter gene in vitro

Hereditary persistence, of fetal hemoglobin is an uncommon, benign disorder in which the expression of gamma -globin genes persists into adult life. Several point mutations have been associated with the increased gamma -globin gene promoter activity. We evaluated the -195 (C-->G) mutation by a functional in vitro assay based on the luciferase reporter gene system. The results indicated that the increased promoter activity observed in vivo could not be reproduced in vitro, under the conditions employed, suggesting that other factors may be involved in the overexpression of the gamma -globin gene containing the -195 (C-->G) mutation. Furthermore: this is the first time that the -195 (C-->G) mutation of the (A)gamma -globin gene has been evaluated by in vitro gene expression.34448949

5D gravitational waves from complexified black rings

In this paper we construct and briefly study the 5D time-dependent solutions of general relativity obtained via double analytic continuation of the black hole (Myers-Perry) and of the black ring solutions with a double (Pomeransky-Senkov) and a single rotation (Emparan-Reall). The new solutions take the form of a generalized Einstein-Rosen cosmology representing gravitational waves propagating in a closed universe. In this context the rotation parameters of the rings can be interpreted as the extra wave polarizations, while it is interesting to state that the waves obtained from Myers-Perry Black holes exhibit an extra boost-rotational symmetry in higher dimensions which signals their better behavior at null infinity. The analogue to the C-energy is analyzed.Comment: 18 pages, 4 figures. References added, introduction and conclusions are amended, some issues related to singularity structure and symmetries are discussed. Matches the print version to appear in JHE

Machine-Part cell formation through visual decipherable clustering of Self Organizing Map

Machine-part cell formation is used in cellular manufacturing in order to process a large variety, quality, lower work in process levels, reducing manufacturing lead-time and customer response time while retaining flexibility for new products. This paper presents a new and novel approach for obtaining machine cells and part families. In the cellular manufacturing the fundamental problem is the formation of part families and machine cells. The present paper deals with the Self Organising Map (SOM) method an unsupervised learning algorithm in Artificial Intelligence, and has been used as a visually decipherable clustering tool of machine-part cell formation. The objective of the paper is to cluster the binary machine-part matrix through visually decipherable cluster of SOM color-coding and labelling via the SOM map nodes in such a way that the part families are processed in that machine cells. The Umatrix, component plane, principal component projection, scatter plot and histogram of SOM have been reported in the present work for the successful visualization of the machine-part cell formation. Computational result with the proposed algorithm on a set of group technology problems available in the literature is also presented. The proposed SOM approach produced solutions with a grouping efficacy that is at least as good as any results earlier reported in the literature and improved the grouping efficacy for 70% of the problems and found immensely useful to both industry practitioners and researchers.Comment: 18 pages,3 table, 4 figure

The influence of semantic and phonological factors on syntactic decisions: An event-related brain potential study

During language production and comprehension, information about a word's syntactic properties is sometimes needed. While the decision about the grammatical gender of a word requires access to syntactic knowledge, it has also been hypothesized that semantic (i.e., biological gender) or phonological information (i.e., sound regularities) may influence this decision. Event-related potentials (ERPs) were measured while native speakers of German processed written words that were or were not semantically and/or phonologically marked for gender. Behavioral and ERP results showed that participants were faster in making a gender decision when words were semantically and/or phonologically gender marked than when this was not the case, although the phonological effects were less clear. In conclusion, our data provide evidence that even though participants performed a grammatical gender decision, this task can be influenced by semantic and phonological factors

Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology.

Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form

Reduction of elasmobranch by-catch in the hake semipelagic near-bottom longline fishery in the Algarve (Southern Portugal)

Elasmobranch fish, particularly deep-sea sharks, are the most important component of the by-catch of the hake semipelagic near-bottom 'pedra-e-bola' longline fishery in the Algarve (South Portugal) and most of these fish are discarded. The effects of the removal of the lower hooks were evaluated, in terms of target and by-catch reductions, by quantifying the catches of each hook relative to the distance from the bottom. The analysis showed that most European hake (Merluccius merluccius), the target species of this fishery, were caught in the middle range of the hooks, with very few individuals caught near the bottom, whereas for sharks the situation was the opposite, with most hooked near the bottom. The removal of the lower three pairs of hooks would result in a small reduction in the catch of the target species, but a much more significant reduction in elasmobranch by-catch. In the specific case of the blackmouth catshark (Galeus melastomus), discard mortality would be further minimized due to the fact that the lower hooks capture significantly smaller animals that are always discarded compared with hooks that are more distant from the bottom

International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI protocol

Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature. There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6–7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed

Identifying people at high risk for developing sleep apnea syndrome (SAS): a cross-sectional study in a Pakistani population

<p>Abstract</p> <p>Background</p> <p>Obstructive Sleep Apnea (OSA) is associated with many cardiovascular and psychiatric diseases. Day-time sleepiness is a common consequence of sleep apnea and correlates with road-traffic accidents (RTA). Pakistan has a high prevalence of factors which predispose an individual to OSA and death from RTAs are a huge burden. However there is a dearth of prevalence studies in this regard. We aim to understand local relevance of the disease and estimate the prevalence of individuals high-risk for OSA.</p> <p>Methods</p> <p>This cross-sectional survey was conducted among 450 individuals at Aga Khan University Hospital (AKUH), which is a tertiary care teaching hospital in Pakistan. We used the BQ as our measurement tool. Based on the responses, participants were grouped into high or low-risk for OSA.</p> <p>Results</p> <p>Our study sample size was 418 with 63.2% males. Mean age of our study population was 30.4 SD +/- 12.3 years; and mean BMI was 23.2 SD +/- 5 kg/m2. Out of the total sample size 24.9% reported snoring and there were twice as many males who snored as compared to females. Forty-five individuals reported that they had nodded off to sleep while driving at least once in their lifetime. On the other hand, the highest proportion of high risk individuals 47.6% was found in the age group 60 or above. The overall prevalence of individuals who were high risk for sleep apnea was 10%.</p> <p>Conclusion</p> <p>A significant proportion of the population is at high-risk for OSA. Our study shows that despite low BMI and favorable craniofacial anatomy sleep apnea is still a locally relevant disease. Given the local relevance of OSAS, it is important to increase awareness among general population but more importantly among physicians of the developing countries, like Pakistan, about common clinical features and pertinent risk factors and complications of OSAS.</p

Quality of life in perimenopausal women working in the health and educational system

The objective of this study was to determine the association between the professional activity and the perceived quality of life in climacteric women who work in Health and Education. A descriptive and cross-sectional study was developed in a sample of 203 climacteric women, together with a correlation analysis of labor factors’ influence on health-related quality of life. Significant differences were found between working women’s quality of life and some labor conditions. The perceived quality of life in perimenopausal women who work in Education is higher than that of those working in Health (p=0.004). Nursing professionals can develop health programs that deal with the work conditions that negatively influence the perceived quality of life in climacteric women.El objetivo de este estudio fue determinar la asociación entre la actividad profesional y la calidad de vida percibida en mujeres climatéricas que trabajan en las áreas sanitaria y educativa. Se realizó un estudio descriptivo y transversal, en una muestra de 203 mujeres climatéricas, junto al análisis correlacional de la influencia de los factores laborales en la calidad de vida relacionada con la salud. Se encontraron diferencias significativas entre la calidad de vida de las trabajadoras y algunas condiciones laborales. La calidad de vida percibida por las mujeres perimenopáusicas que trabajan en educación es superior a la de las que trabajan en salud (p=0,004). Los profesionales de Enfermería pueden elaborar programas de salud, que aborden las condiciones de trabajo que influyen negativamente en la calidad de vida percibida por las mujeres climatéricas.O objetivo deste estudo foi determinar a associação entre a atividade profissional e a qualidade de vida percebida em mulheres climatéricas que trabalham nas áreas da saúde e educação. Realizou-se estudo descritivo e transversal, numa amostra de 203 mulheres climatéricas, juntamente com análise correlacional da influência dos fatores de trabalho na qualidade de vida, relacionada à saúde. Encontraram-se diferenças significativas entre a qualidade de vida das trabalhadoras e algumas variáveis laborais. A qualidade de vida percebida pelas mulheres perimenopáusicas que trabalham na área da educação é superior à daquelas que trabalham na área da saúde (p=0,004). Os profissionais de enfermagem podem elaborar programas de saúde que abordem as condições de trabalho que influenciam negativamente a qualidade de vida percebida pelas mulheres climatéricas