Renowned for his influence as a political philosopher, a writer, and an autobiographer, Jean-Jacques Rousseau is known also for his lifelong interest in music. He composed operas and other musical ...pieces, invented a system of numbered musical notation, engaged in public debates about music, and wrote at length about musical theory. Critical analysis of Rousseau’s work in music has been principally the domain of musicologists, rarely involving the work of scholars of political theory or literary studies. In Rousseau Among the Moderns, Julia Simon puts forth fresh interpretations of The Social Contract, the Discourse on the Origin of Inequality, and the Confessions, as well as other texts. She links Rousseau’s understanding of key concepts in music, such as tuning, harmony, melody, and form, to the crucial problem of the individual’s relationship to the social order. The choice of music as the privileged aesthetic object enables Rousseau to gain insight into the role of the aesthetic realm in relation to the social and political body in ways often associated with later thinkers. Simon argues that much of Rousseau’s “modernism” resides in the unique role that he assigns to music in forging communal relations.
Genetics of Cushing's disease Simon, Julia; Theodoropoulou, Marily
Journal of neuroendocrinology,
August 2022, Volume:
34, Issue:
8
Journal Article
Peer reviewed
Open access
Corticotroph tumours are primarily sporadic monoclonal neoplasms and only rarely found in genetic syndromes. Recurrent mutations in the ubiquitin specific protease 8 (USP8) gene are found in around ...half of cases. Mutations in other genes such as USP48 and NR3C1 are less frequent, found in less than ~20% of cases. TP53 and ATXR mutations are reported in up to one out of four cases, when focusing in USP8 wild type or aggressive corticotroph tumours and carcinomas. At present, USP8 mutations are the primary driver alterations in sporadic corticotroph tumours, TP53 and ATXR mutations may indicate transition to more aggressive tumour phenotype. Next generation sequencing efforts have identified additional genomic alterations, whose role and importance in corticotroph tumorigenesis remains to be elucidated.
Abstract
Background
Long COVID is defined as the persistence of symptoms beyond 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To better understand the ...long-term course and etiology of symptoms we analyzed a cohort of patients with COVID-19 prospectively.
Methods
Patients were included at 5 months after acute COVID-19 in this prospective, noninterventional, follow-up study. Patients followed until 12 months after COVID-19 symptom onset (n = 96; 32.3% hospitalized, 55.2% females) were included in this analysis of symptoms, quality of life (based on an SF-12 survey), laboratory parameters including antinuclear antibodies (ANAs), and SARS-CoV-2 antibody levels.
Results
At month 12, only 22.9% of patients were completely free of symptoms and the most frequent symptoms were reduced exercise capacity (56.3%), fatigue (53.1%), dyspnea (37.5%), and problems with concentration (39.6%), finding words (32.3%), and sleeping (26.0%). Females showed significantly more neurocognitive symptoms than males. ANA titers were ≥1:160 in 43.6% of patients at 12 months post–COVID-19 symptom onset, and neurocognitive symptom frequency was significantly higher in the group with an ANA titer ≥1:160 versus <1:160. Compared with patients without symptoms, patients with ≥1 long-COVID symptom at 12 months did not differ significantly with respect to their SARS-CoV-2 antibody levels but had a significantly reduced physical and mental life quality compared with patients without symptoms.
Conclusions
Neurocognitive long-COVID symptoms can persist ≥1 year after COVID-19 symptom onset and reduce life quality significantly. Several neurocognitive symptoms were associated with ANA titer elevations. This may indicate autoimmunity as a cofactor in etiology of long COVID.
Neurocognitive long-COVID symptoms can persist at least for 1 year after acute COVID-19 and reduce life quality significantly. Several neurocognitive symptoms were associated with ANA titer elevations. This may indicate autoimmunity as a cofactor in the etiology of long COVID.
Despite a multitude of p53 immunohistochemistry (IHC) studies, data on the combined effect of nuclear p53 protein accumulation and TP53 genomic inactivation are lacking for prostate cancer. A tissue ...microarray including 11,152 prostate cancer samples was analyzed by p53 IHC and fluorescence in situ hybridization. Nuclear p53 accumulation was found in 10.1% of patients including 1.4% with high‐level and 8.7% with low‐level immunostaining. TP53 sequencing revealed that 17 of 22 (77%) cases with high‐level p53 immunostaining, but only 3% (1 of 31) low‐level p53 cases carried putative dominant‐negative mutations. TP53 deletions occurred in 14.8% of cancers. Both deletions and protein accumulation were linked to unfavorable tumor phenotype and prostate specific antigen (PSA) recurrence (p < 0.0001 each). The combination of both methods revealed subgroups with remarkable differences in their clinical course. Tumors with either TP53 deletion (14%) or low‐level p53 positivity (8.7%) had identical risks of PSA recurrence, which were markedly higher than in cancers without p53 alterations (p < 0.0001). Tumors with both p53 deletion and low‐level p53 positivity (1.5%) had a worse prognosis than patients with only one of these alterations (p < 0.0001). Tumors with strong p53 immunostaining or homozygous inactivation through deletion of one allele and disrupting translocation involving the second allele had the worst outcome, independent from clinical and pathological parameters. These data demonstrate a differential clinical impact of various TP53 alterations in prostate cancer. Strong p53 immunostaining—most likely accompanying dominant negative or oncogenic p53 mutation—has independent prognostic relevance and may thus represent a clinical useful molecular feature of prostate cancer.
What's New?
Despite a multitude of p53 immunohistochemistry studies, data on the combined effect of nuclear p53 protein accumulation and TP53 genomic inactivation are lacking for prostate cancer. Here, a tissue microarray including 11,000 prostate cancer samples was analyzed by p53 immunohistochemistry and fluorescence in‐situ hybridization. The data demonstrate that different types of TP53 defects impact the clinical course of the disease differently. Strong nuclear p53 protein accumulation, or complete genomic inactivation through deletion of one allele and breakage of the second, characterized a patient subgroup with inferior outcome independently from other established prognostic parameters, thus potentially representing clinically useful molecular parameters.
Background
The authors developed a pain monitoring app offering educational information, and real‐time health care professional feedback on clinically significant pain (>4 numeric rating scale ...NRS‐11) for children with cancer to reduce pain at home.
Methods
This monocenter, nonblinded randomized controlled trial enrolled Dutch children (0–18 years old) receiving cancer treatment (≥3 months after diagnosis, ≥2 months treatment remaining). Children were randomly assigned to use the app or receive usual care (two parallel groups). We assessed whether use of the app yielded less clinically significant pain (aim 1) and whether it affected pain severity, duration, interference, pain management strategies, and parental emotional well‐being (aim 2). The app was also evaluated by families (aim 3).
Results
A total of 94 children were randomized to use the app (15 drop‐outs), and 90 were to receive care as usual (11 drop‐outs). The app group (n = 79, mean age: 7.5 5.1 years, 48% girls, 63% hemato‐oncology diagnosis) reported significantly less clinically significant pain compared to usual care (n = 79, mean age: 7.5 5.4 years, 52% girls, 65% hemato‐oncology diagnosis) (odds ratio OR, 0.38; 95% confidence interval CI, 0.198–0.734) (aim 1), as well as significantly lower pain severity (β = –0.27; 95% CI, –0.407 to –0.142). No differences were found for duration, interference, or management strategies. Parents in the app group reported significantly less distress compared to usual care (β = –0.84; 95% CI, –1.61 to –0.03) (aim 2). Families generally evaluated the app positively (aim 3).
Conclusions
Use of the app resulted in less clinically significant pain at home. The exact working mechanisms of the app should be further elucidated.
Use of a pain monitoring app with educational information on pain (management) and real‐time health care professional feedback reduced clinically significant pain in children with cancer at home.
Purpose
This study assessed adherence to, feasibility of, and barriers and facilitators of implementation of an app developed to monitor and follow-up with pain in children with cancer at home.
...Methods
Children (8–18 years) receiving cancer treatment (all diagnoses) or their parents (of children aged 0–7 years) used the KLIK Pain Monitor app for 3 weeks. Pain was assessed twice daily using an 11-point numeric rating scale (NRS-11) (ranging from 0 to 10). Healthcare professionals (HCP’s) from the hospital’s Pediatric Pain Service were instructed to follow-up with clinically significant pain scores (≥ 4) within 120 min (scores 4–6) or 30 min (scores 7–10). Adherence, feasibility, and implementation outcomes were assessed using questionnaires, app log data, and interviews.
Results
Twenty-seven children (
M
age = 7.3 years, 51.8% male) and six HCP’s participated. Sixty-three percent (
N
= 17) of families used the app on a daily basis during three weeks, and 18.5% (
N
= 5) reported pain scores twice daily during that time (
family adherence
). Twelve out of 27 children (44.4%) reported a clinically significant pain score at least once. In 70% (14/20) of clinically significant pain scores, HCP’s followed-up with families within the set timeframe (
HCP adherence
). Outcomes reveal feasibility for the majority of app functions (i.e., positive evaluation by ≥ 70% families/HCP’s), and non-feasible aspects could be resolved. Identified barriers and facilitators were used to improve future implementation efforts.
Conclusion
Use of the KLIK Pain Monitor app seems feasible. Future research will determine its effectiveness in reducing pain in children with cancer at home.
The requirements of evidence-based content in the lesson preparation gain great significance in nursing education regarding the current trends and developments to further professionalize the nursing ...care profession. Within their daily practice, nurse practitioners are already supposed to implement evidence-based practice and take a well informed health care decision influenced by nursing science. The future available nursing education programs in Germany, determined by law, will encompass the existing vocational training and an academic study program. The central reference discipline in the education programs, as well as in the teacher study programs, will be nursing science. Consensus on mutual scientific knowledge requirements for academic planning differs due to the heterogeneous education of the nurse educators along with the current uncertain state about the classification of nursing science and the didactic intervention its discipline. The following dissertation will present, grounded to the previous stated problem how far scientific findings are implemented in the content-related lesson planning and in the tuition of nurse teachers. The presented extensive data analysis, based on the research methodology of Grounded Theory, provides a theoretical model about scientific requirements in the lesson planning in nursing education as well as recommendations to stimulate further reflection and design.
•Two latency windows emerged being sensitive to ISI change (150–170 and 210–230 ms).•TOJ thresholds correlated with amplitude change 210–230 ms post stimulus.•The “high-threshold” (low performance) ...group showed pronounced amplitude change.
The study investigated auditory temporal processing on a tens of milliseconds scale that is the interval when two consecutive stimuli are processed either together or as distinct events. Distinctiveness is defined by one’s ability to make correct order judgments of the presented sounds and is measured via the spatial temporal order judgement task (TOJ).
The study aimed to identify electrophysiological indices of the TOJ performance. Tone pairs were presented with inter-stimulus intervals (ISI) varying between 25 and 75 ms while EEG was recorded. A pronounced amplitude change in the P2 interval was found between the event-related potential (ERP) of tone pairs having ISI = 55 and 65 ms, but it was a characteristic only of the group having poor behavioral thresholds. With the two groups combined, the amplitude change between these ERPs in the P2 interval showed a medium-size correlation with the behavioral threshold.
INTRODUCTION Perhaps no rules of evidence are as contested as the rules governing character evidence.1 To ward off the danger of a fact finders mistaking evidence of character for evidence of action, ...the rules exclude much contextual information about the people at the center of the proceeding.2 This prohibition on character propensity evidence is a bedrock principle of American law.3 Yet despite its centrality, it is uncertain of both content and application.· · · 4 Contributing to this uncertainty is a definitional lacuna. In offering this framing of the problem and proposed solution, I am influenced by feminist and inter sectional feminist thinkers as well as critical race theorists who have exposed how the legal system assumes white men as the baseline.10 The past five decades of scholarly critique of the character evidence rules bear out the existence of a baseline figure. Most prominently, Rule 404 prohibits propensity evidence.20 There are some exceptions when defendants or victims put their characters at issue in a criminal case.21 And there is a glaring reversal of the prohibition for defendants accused of sexual assault.22 The rules also try to make clear that evidence that would otherwise look like character evidence is admissible for a nonpropensity purpose, such as showing that the defendant had the knowledge to commit a particular crime.23 But the character evidence rules do not stop there. Rule 404 also incorporates by reference Rule 609, which permits the impeachment of witnesses with evidence of prior convictions subject to balancing tests that have been increasingly interpreted to favor admissibility.24 Under Rule 608, also incorporated by reference in Rule 404, witnesses can be called to impeach another witness's character for truthfulness or to testify to a witness's character for truthfulness once that character has been attacked.25 No Federal Rule makes explicit reference to demeanor.
Background
Pain is a common symptom in childhood cancer. Since children spend more time at home, families are increasingly responsible for pain management. This study aimed at assessing pain at home.
...Procedure
In this longitudinal observational study (April 2016‐January 2017), pain severity and prevalence, analgesic use, and pain interference with daily life (Brief Pain Inventory Short Form) were assessed for 4 consecutive days around the time of multiple chemotherapy appointments. Descriptive statistics (frequencies and percentages) were used to report pain severity (with clinically significant pain defined as: score ≥ 4 on “worst pain” or “average pain in the last 24 h”), pain prevalence, and analgesic use. Mixed models were estimated to assess whether patient characteristics were associated with pain severity, and whether pain severity was associated with interference with daily life.
Results
Seventy‐three children (50.7% male) participated (1‐18 years). A majority (N = 57, 78%) experienced clinically significant pain at least once, and 30% reported clinically significant pain at least half the time. In 33.6% of scores ≥ 4, no medication was used. We found an association between pain severity and interference with daily life: the higher the pain, the bigger the interference (estimated regression coefficient = 1.01 95% CI 0.98‐1.13).
Conclusions
The majority of children experienced clinically significant pain at home, and families frequently indicated no medication use. A stronger focus on education and coaching of families seems essential, as well as routine screening for pain in the home setting.
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