No effect of remdesivir or betamethasone on upper respiratory tract SARS-CoV-2 RNA kinetics in hospitalised COVID-19 patients: a retrospective observational study

Background The viral kinetics of SARS-CoV-2 has been considered clinically important. While remdesivir and corticosteroids are recommended for COVID-19 patients requiring oxygen support, there is a limited number of published reports on viral kinetics in hospitalised patients with COVID-19 treated with remdesivir or corticosteroids. Methods We conducted a retrospective study by collecting longitudinal samples from the nasopharynx/throat of 123 hospitalised patients (median age 55 years, 74% male) with COVID-19, to evaluate the effects of remdesivir and corticosteroid treatment on viral RNA levels. The subjects were divided into four groups: those receiving remdesivir (n = 25), betamethasone (n = 41), both (n = 15), or neither (n = 42). Time to viral RNA clearance was analysed using Kaplan-Meier plots, categorical data were analysed using Fisher\u27s exact test, and Kruskal-Wallis for continuous data. Viral RNA decline rate was analysed using a mixed effect model. Results We found no significant difference in SARS-CoV-2 RNA decline rate or time to SARS-CoV-2 RNA clearance between the groups. Moreover, clinical status at baseline was not correlated with time to viral clearance. Conclusions Since SARS-CoV-2 RNA kinetics was not affected by treatment, repeated sampling from the upper respiratory tract cannot be used to evaluate treatment response

Spatio-temporal analysis of prostate tumors in situ suggests pre-existence of treatment-resistant clones

The molecular mechanisms underlying lethal castration-resistant prostate cancer remain poorly understood, with intratumoral heterogeneity a likely contributing factor. To examine the temporal aspects of resistance, we analyze tumor heterogeneity in needle biopsies collected before and after treatment with androgen deprivation therapy. By doing so, we are able to couple clinical responsiveness and morphological information such as Gleason score to transcriptome-wide data. Our data-driven analysis of transcriptomes identifies several distinct intratumoral cell populations, characterized by their unique gene expression profiles. Certain cell populations present before treatment exhibit gene expression profiles that match those of resistant tumor cell clusters, present after treatment. We confirm that these clusters are resistant by the localization of active androgen receptors to the nuclei in cancer cells post-treatment. Our data also demonstrates that most stromal cells adjacent to resistant clusters do not express the androgen receptor, and we identify differentially expressed genes for these cells. Altogether, this study shows the potential to increase the power in predicting resistant tumors

Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders

Background To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset. Methods SARS-CoV-2-specific IgG antibody levels were quantified using two clinically validated and widely used commercial serological assays (Architect, Abbott Laboratories and iFlash 1800, YHLO), detecting antibodies against the spike and nucleocapsid proteins. Results Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P= 0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset. Conclusions Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys

Spatially resolved clonal copy number alterations in benign and malignant tissue

Publisher Copyright: © 2022, The Author(s).Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer1. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics2 to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.Peer reviewe

Spatially resolved clonal copy number alterations in benign and malignant tissue

Publisher Copyright: © 2022, The Author(s).Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer1. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics2 to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.Peer reviewe

The effects of CSR initiatives and CSR communication on customers’ responses and satisfaction : a quantitative study examining Systembolaget’s CSR

Corporate social responsibility (CSR) has lately grown to be a well-researched area and most companies engage in social responsibilities to some extent. It has been shown that companies’ CSR and CSR communication affects consumer responses. Some of these responses have also been seen to be affected by the customers’level of support for CSR, and specific issues in particular, as well as their perceived fit between a company and a cause. The purpose of this thesis is to examine the impact CSR initiatives andCSR communication has on customers’ responses and satisfaction. Whether the customers are supportive of CSR and specific CSR issues will, along with the Perceived fit of the company and the cause, also be examined. The responses we will be examining are awareness, attitudes, attributions and perceptions. To make a practical contribution this will be executed in relation to the Government monopoly Systembolaget. This specific company does not work according to a profit maximizing motive but is depended on continued support from the Swedish population to be able to keep their mandate. Thus, they are also in need of satisfied customers and therefore the focus of this study will be on satisfaction related to the company’s CSR work.A research gap was detected,thus there are no previous research examining the factors employed in this research as a collective or of the specific company-context, i.e. a Government monopoly without an aim to profit-maximize. Hence, we could see that more research is needed on the area of consumers’perspectives regarding CSR and CSR communication, and especially in the monopoly context. In order for us to fulfill the purpose of this study, we conducted a quantitative study involving Systembolaget'scustomers. The results showed that perceived fit between the company and the supported causes had a significant positive effect on respondents’attitudes. These attitudes were in turn the factor showing the most significant, positive effect on customer satisfaction. Furthermore, the findings showed that both perceptions and awareness had a significant, positive effect on customer satisfaction, even though the effect was not as big. From our findings we could also conclude that Systembolaget have not reached their optimal level of either CSR or CSR communication. We therefore provided Systembolaget with some practical recommendations for how to proceed with their CSR work and proposed suggestions for improvement

Natura 2000-tillstånd vid bearbetningskoncession : En komplex process med parallella prövningar

Den nuvarande prövningsordningen för bearbetningskoncession bygger på ett system där Bergsstaten bedömer företrädesrätt till mineral och mark- och vattenområden. Prospektören måste senare ansöka om miljötillstånd enligt miljöbalken. Problem uppstår när de parallella prövningarna kolliderar med EU:s skydd för utpekade arter och livsmiljöer (Natura 2000). Risken med att vid ett tidigt skede i processen ansöka om Natura 2000-tillstånd är att man behöver söka nytt tillstånd senare i processen, detta om gruvverksamhetens omfattning och miljöeffekter inte var fullt klarlagda vid det första ansökningstillfället. Dessa omständigheter har resulterat i en rättsosäkerhet och att färre gruvor etableras. Arbetet har tagit utgångspunkt ifrån analyser av gällande rätt och har genom en rättsdogmatisk metod syftat till att redogöra för förutsättningarna för att erhålla bearbetningskoncession. Vidare har arbetet avsett att undersöka när i prövningsprocessen ett Natura 2000-tillstånd behöver sökas samt vilka kriterier som behöver vara uppfyllda för att erhålla tillståndet. De parallella prövningarna samt nuvarande prövningsordning har blivit ett problem som givit upphov till ett lagförslag som föreslår att ett Natura 2000-tillstånd inte längre ska vara en förutsättning för att erhålla bearbetningskoncession. Natura 2000-tillståndsprövningen ska istället interageras med miljötillståndsprövningen som sker vid ett senare tillfälle. De tilltänkta ändringarna syftar till att effektivisera prövningsprocessen samt bidra till att den ska bli mer förutsägbar och rättssäker, detta i sin tur antas leda till att investeringsviljan ökar. Lagändringen antas inte leda till några negativa effekter på miljön eftersom en koncession inte per automatik innebär tillstånd att starta en gruvverksamhet, den utgör heller ingen garanti för att verksamheten kommer godkännas i slutändan. Kraven på tillstånd enligt miljöbalken kvarstår och lagstiftarens syfte är endast att ändra när i tillståndsprövningen ansökan ska ske

The effects of CSR initiatives and CSR communication on customers’ responses and satisfaction : a quantitative study examining Systembolaget’s CSR

Corporate social responsibility (CSR) has lately grown to be a well-researched area and most companies engage in social responsibilities to some extent. It has been shown that companies’ CSR and CSR communication affects consumer responses. Some of these responses have also been seen to be affected by the customers’level of support for CSR, and specific issues in particular, as well as their perceived fit between a company and a cause. The purpose of this thesis is to examine the impact CSR initiatives andCSR communication has on customers’ responses and satisfaction. Whether the customers are supportive of CSR and specific CSR issues will, along with the Perceived fit of the company and the cause, also be examined. The responses we will be examining are awareness, attitudes, attributions and perceptions. To make a practical contribution this will be executed in relation to the Government monopoly Systembolaget. This specific company does not work according to a profit maximizing motive but is depended on continued support from the Swedish population to be able to keep their mandate. Thus, they are also in need of satisfied customers and therefore the focus of this study will be on satisfaction related to the company’s CSR work.A research gap was detected,thus there are no previous research examining the factors employed in this research as a collective or of the specific company-context, i.e. a Government monopoly without an aim to profit-maximize. Hence, we could see that more research is needed on the area of consumers’perspectives regarding CSR and CSR communication, and especially in the monopoly context. In order for us to fulfill the purpose of this study, we conducted a quantitative study involving Systembolaget'scustomers. The results showed that perceived fit between the company and the supported causes had a significant positive effect on respondents’attitudes. These attitudes were in turn the factor showing the most significant, positive effect on customer satisfaction. Furthermore, the findings showed that both perceptions and awareness had a significant, positive effect on customer satisfaction, even though the effect was not as big. From our findings we could also conclude that Systembolaget have not reached their optimal level of either CSR or CSR communication. We therefore provided Systembolaget with some practical recommendations for how to proceed with their CSR work and proposed suggestions for improvement