What do people affected by amyotrophic lateral sclerosis want from health communications? Evidence from the ALS Talk project

Introduction/aims: Health communication is central to effective, supportive amyotrophic lateral sclerosis (ALS) clinical care. Guidance for ALS communication is limited, focuses on diagnosis disclosure, and frequently relies on expert consensus and/or reviews. Patient-based evidence is needed to guide ALS health communication. We investigated how the experiences of ALS patients and family caregivers can inform effective communication practices from diagnosis to end-of-life.Methods: Data were drawn from the ALS Talk Project, an asynchronous, online focus group study. Seven focus groups and five interviews (105 participants) were conducted. Data were qualitatively analyzed using directed content analysis and the constant-comparative approach.Results: We found four primary themes: communication content, communication circumstances, information sufficiency, and communication manner. Data indicate participants relied on clinicians for medical information but also wanted practical information; health communication should attend to the circumstances within which conversations occur; information must be sufficient for individual needs, without overwhelming; and an empathetic, direct, and honest manner facilitated trust. Participants identified communication challenges and strategies to improve communication across major themes, including stepwise approaches and conversations tailored to individuals and their heterogeneous disease experiences.Discussion: Healthcare professionals should discuss patient/caregiver communication preferences early in the therapeutic relationship, co-develop a communication agreement, and update the agreement in response to changing needs and disease progression. This will foster regular discussion of information needs and promote timely discussions of challenging topics, including advance care, while giving patients and families a sense of control. Findings may have implications for other neuromuscular disease and/or seriously ill populations

Effects of environmental factors on development of Pyrenopeziza brassicae (light leaf spot) apothecia on oilseed rape debris

Publication no. P-2001-0221-01R. This article is in the public domain and not copyrightable. It may be freely reprinted with customary crediting of the source. The American Phytopathological Society, 2001The development of Pyrenopeziza brassicae (light leaf spot) apothecia was studied on petiole debris from artificially infected oilseed rape leaves incubated at temperatures from 6 to 22 degreesC under different wetness regimes and in 16 h light/8 h dark or continuous darkness. There was no significant difference between light treatments in numbers of apothecia that developed. Mature apothecia developed at temperatures from 5 to 18 degreesC but not at 22 degreesC. The rate of apothecial development decreased as temperature decreased from 18 to 5 degreesC; mature apothecia were first observed after 5 days at 18 degreesC and after 15 days at 6 degreesC. Models were fitted to estimates of the time (days) for 50% of the maximum number of apothecia to develop (t(1); model 1, t(1) = 7.6 + 55.8(0.839)(T)) and the time for 50% of the maximum number of apothecia to decay (t(2); model 2, t(2) = 24.2 + 387(0.730)(T)) at temperatures (T) from 6 to 18 degreesC. An interruption in wetness of the petiole debris for 4 days after 4, 7, or 10 days of wetness delayed the time to observation of the first mature apothecia for approximate to4 days and decreased the number of apothecia produced (by comparison with continuous wetness). A relationship was found between water content of pod debris and electrical resistance measured by a debris-wetness sensor. The differences between values of tl predicted by model 1 and observed values of t(1) were 1 to 9 days. Model 2 did not predict t(2); apothecia decayed more quickly under natural conditions than predicted by model 2.Peer reviewe

Asynchronous online focus groups for research with people living with amyotrophic lateral sclerosis and family caregivers: Usefulness, acceptability and lessons learned

Background: People with amyotrophic lateral sclerosis (ALS) face disability- and travel-related barriers to research participation. We investigate the usefulness and acceptability of asynchronous, online focus groups (AOFGs) for research involving people affected by ALS (patients and family caregivers) and outline lessons learned.Methods: The ALS Talk Project, consisting of seven AOFGs and 100 participants affected by ALS, provided context for this investigation. Hosted on the secure itracks Board™ platform, participants interacted in a threaded web forum structure. Moderators posted weekly discussion questions and facilitated discussion. Data pertaining to methodology, participant interaction and experience, and moderator technique were analyzed using itracks and NVivo 12 analytics (quantitative) and conventional content analysis and the constant-comparative approach (qualitative).Results: There was active engagement within groups, with post lengths averaging 111.48 words and a complex network of branching interactions between participants. One third of participant responses included individual reflections without further interaction. Participants affirmed their co-group members, offered practical advice, and discussed shared and differing perspectives. Moderators responded to all posts, indicating presence and probing answers. AOFGs facilitated qualitative and quantitative data-gathering and flexible response to unanticipated events. Although total participation fell below 50% after 10–12 weeks, participants valued interacting with peers in an inclusive, confidential forum. Participants used a variety of personal devices, browsers, and operating systems when interacting on the online platform.Conclusions: This methodological examination of AOFGs for patient-centred investigations involving people affected by ALS demonstrates their usefulness and acceptability, and advances knowledge of online research methodologies. Lessons learned include: early identification of research goals and participant needs is critical to selecting an AOFG platform; although duration longer than 10–12 weeks may be burdensome in this population, participants were positive about AOFGs; AOFGs offer real world flexibility enabling response to research challenges and opportunities; and, AOGFs can effectively foster safe spaces for sharing personal perspectives and discussing sensitive topics. With moderators playing an important role in fostering engagement, AOFGs facilitated rich data gathering and promoted reciprocity by fostering the exchange of ideas and interaction between peers. Findings may have implications for research involving other neurologically impaired and/or medically vulnerable populations

Quantitative Trait Locus Mapping of Winter Hardiness Metabolites in Autotetraploid Alfalfa (M. sativa)

In winter hardy alfalfa cultivars, cold acclimation occurs prior to the onset of freezing temperatures and normally is accompanied with a series of metabolic and morphological adjustments. We are studying the accumulation pattern of metabolites throughout the autumn previous to freezing and relating them to winter survival in an Fl segregating population between the cross of M. sativa subsp. sativa and subsp. falcata. Morphological components and soluble carbohydrates, protein, amino-N groups, and free fatty acids were measured in 2001 and 2002 in the field. Broad sense heritability was intermediate for shoot and root mass and height, and for metabolites, ranged from low (TNC=0.04) to high (starch=0.80). The genetic correlation between winter injury was not significant for most of the metabolites, except for soluble protein and amino-N group concentrations. The presence of allele al of MSAIC B, a cold-related gene, was positively associated with autumn plant height but negatively associated with root mass in the WISFAL-6 parent. Numerous QTL were detected for concentrations of metabolites. Our results suggest that winter injury and autumn biomass are controlled by different loci in this population

Averages of b-hadron Properties at the End of 2005

This article reports world averages for measurements on b-hadron properties obtained by the Heavy Flavor Averaging Group (HFAG) using the available results as of at the end of 2005. In the averaging, the input parameters used in the various analyses are adjusted (rescaled) to common values, and all known correlations are taken into account. The averages include lifetimes, neutral meson mixing parameters, parameters of semileptonic decays, branching fractions of B meson decays to final states with open charm, charmonium and no charm, and measurements related to CP asymmetries

Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway.

A promising new compound class for treating human malaria is the imidazolopiperazines (IZP) class. IZP compounds KAF156 (Ganaplacide) and GNF179 are effective against Plasmodium symptomatic asexual blood-stage infections, and are able to prevent transmission and block infection in animal models. But despite the identification of resistance mechanisms in P. falciparum, the mode of action of IZPs remains unknown. To investigate, we here combine in vitro evolution and genome analysis in Saccharomyces cerevisiae with molecular, metabolomic, and chemogenomic methods in P. falciparum. Our findings reveal that IZP-resistant S. cerevisiae clones carry mutations in genes involved in Endoplasmic Reticulum (ER)-based lipid homeostasis and autophagy. In Plasmodium, IZPs inhibit protein trafficking, block the establishment of new permeation pathways, and cause ER expansion. Our data highlight a mechanism for blocking parasite development that is distinct from those of standard compounds used to treat malaria, and demonstrate the potential of IZPs for studying ER-dependent protein processing

Optically controlled 2D tunnelling in GaAs delta-doped p-n junction

A new type of an optically controlled tunnelling process in a specially designed Esaki diode is investigated. The additional peak appears due to tunnelling of 2D electrons accumulated at ground state of delta doped layers embedded nearby the p-n junction into the valence band of the p⁺-contact. It is found that the voltage position of an additional resonant peak shifts to lower bias voltage with increasing both incident light intensity and temperature. Our experimental data and theoretical simulations show that this shift is a result of an electrical field redistribution in the region of the p-n junction caused by non-equilibrium carriers generated with optic or thermal excitation

Elucidating the path to Plasmodium prolyl-tRNA synthetase inhibitors that overcome halofuginone resistance

© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.The development of next-generation antimalarials that are efficacious against the human liver and asexual blood stages is recognized as one of the world's most pressing public health challenges. In recent years, aminoacyl-tRNA synthetases, including prolyl-tRNA synthetase, have emerged as attractive targets for malaria chemotherapy. We describe the development of a single-step biochemical assay for Plasmodium and human prolyl-tRNA synthetases that overcomes critical limitations of existing technologies and enables quantitative inhibitor profiling with high sensitivity and flexibility. Supported by this assay platform and co-crystal structures of representative inhibitor-target complexes, we develop a set of high-affinity prolyl-tRNA synthetase inhibitors, including previously elusive aminoacyl-tRNA synthetase triple-site ligands that simultaneously engage all three substrate-binding pockets. Several compounds exhibit potent dual-stage activity against Plasmodium parasites and display good cellular host selectivity. Our data inform the inhibitor requirements to overcome existing resistance mechanisms and establish a path for rational development of prolyl-tRNA synthetase-targeted anti-malarial therapies.This work was supported by NIH R01AI143723 (R.M. and D.F.W.), NIH R01AI152533 (M.R.L. and E.A.W.), 5F31AI129412 (L.F.), and the Bill & Melinda Gates Foundation (OPP1054480, E.A.W. and D.F.W.), LEAN program of the Leducq Foundation (U.O.), Arthritis Research UK 20522 (U.O.), Cancer Research UK A23900 (U.O.). N.C.P. was supported by a National Science Foundation Graduate Research Fellowship (DGE1745303). M.R.L. was supported in part by a Ruth L. Kirschstein Institutional National Research Award from the National Institute for General Medical Sciences (T32 GM008666). This publication includes data generated at the University of California, San Diego IGM Genomics Center utilizing an Illumina NovaSeq 6000 that was purchased with funding from a National Institutes of Health SIG grant (#S10 OD026929).info:eu-repo/semantics/publishedVersio