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Dynamic face stimuli are increasingly used in face perception research, as increasing evidence shows they are perceived differently from static photographs. One popular method for creating dynamic faces is the dynamic morph, which can animate the transition between expressions by blending two photographs together. Although morphs offer increased experimental control, their unnatural motion differs from the biological facial motion captured in video recordings. This study aimed to compare ratings of emotion intensity and genuineness in video recordings, dynamic morphs, and static photographs of happy, sad, fearful, and angry expressions. We found that video recordings were perceived to have greater emotional intensity than dynamic morphs, and video recordings of happy expressions were perceived as more genuine compared to happy dynamic morphs. Unexpectedly, static photographs and video recordings had similar ratings for genuineness and intensity. Overall, these results suggest that dynamic morphs may be an inappropriate substitute for video recordings, as they may elicit misleading dynamic effects. [ABSTRACT FROM AUTHOR]

Eplontersen (Wainua™) is a ligand-conjugated antisense oligonucleotide directed to TTR, which is being developed by Ionis Pharmaceuticals and AstraZeneca for the treatment of TTR-mediated amyloidosis (ATTR). Eplontersen, which is targeted to the liver by a ligand containing three N-acetyl galactosamine residues, binds to wild-type and variant TTR mRNA, thus reducing the levels of circulating TTR protein and amyloid deposition. Subcutaneous eplontersen reduced serum TTR levels, inhibited neuropathy progression and improved health-related quality of life in patients with polyneuropathy of hereditary ATTR (ATTRv-PN; v for variant) in a phase III trial. Based on these results, eplontersen was approved in the USA for the treatment of ATTRv-PN on 21 December 2023 and is currently undergoing regulatory review for a similar indication in the EU, the UK, Switzerland and Canada. Eplontersen is also undergoing phase III development for ATTR cardiomyopathy. This article summarizes the milestones in the development of eplontersen leading to this first approval for ATTRv-PN. [ABSTRACT FROM AUTHOR]

Casirivimab/imdevimab (Ronapreve™; REGEN-COV™) is a co-packaged combination of two neutralizing immunoglobulin gamma 1 (IgG1) human monoclonal antibodies (casirivimab and imdevimab) against the spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Casirivimab/imdevimab received its first emergency use authorization for the treatment of COVID-19 in November 2020 in the USA, with similar authorizations subsequently granted in various other countries, including India, Canada, and Switzerland. In February 2021, casirivimab/imdevimab was granted a positive scientific opinion in the EU for the treatment of COVID-19. In July 2021, casirivimab/imdevimab received its first approval in Japan for the treatment of mild or moderate COVID-19, followed in August 2021 by its conditional approval for the prophylaxis and treatment of acute COVID-19 infection in the UK. The combination was also granted provisional determination in Australia in August 2021, indicating its eligibility to be considered for provisional registration for COVID-19 treatment and prevention. This article summarizes the milestones in the development of casirivimab/imdevimab leading to these first approvals for COVID-19. [ABSTRACT FROM AUTHOR]

Background: Drug survival analysis of biologic agents in psoriasis is of extreme importance, as it allows not only the evaluation of objective clinical outcomes (such as effectiveness and safety) but also of factors that are associated with patients' adherence to treatment. The aim of this study was to evaluate and compare the drug survival of the most recent biologic agents approved for the treatment of moderate-to-severe psoriasis—ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and risankizumab—and to identify clinical predictors that can influence the drug survival of these drugs. Methods: This retrospective multicentric cohort study from 16 dermatology centers in Portugal, Spain, Italy, Switzerland, Czech Republic, Canada, and the United States included patients that started IL-12/23, IL-17 (IL-17A and IL-17R) and IL-23 inhibitors for the treatment of psoriasis between January 1, 2012 and December 31, 2019. Survival analysis was performed using a Kaplan-Meier estimator, to obtain descriptive survival curves, and proportional hazard Cox regression models. Results: A total of 3312 treatment courses (total patients: 3145) were included in the study; 1118 (33.8%) with an IL-12/23 inhibitor (ustekinumab), 1678 (50.7%) with an IL-17 inhibitor [911 (27.5%) on secukinumab, 651 (19.7%) on ixekizumab, 116 (3.5%) on brodalumab], and 516 (15.5%) with an IL-23 inhibitor [398 (12.0%) on guselkumab, 118 (3.5%) on risankizumab]. At 18 months, the cumulative probability of survival was 96.4% for risankizumab, 91.1% for guselkumab, 86.3% for brodalumab, 86.1% for ustekinumab, 82.0% for ixekizumab, and 79.9% for secukinumab. Using ustekinumab as reference, drug survival of guselkumab was higher (HR 0.609; 95% CI 0.418–0.887) and that of secukinumab was lower (HR 1.490; 95% CI 1.257–1.766). In the final multivariable model, secukinumab, female sex, higher BMI, and prior exposure to biologic agents significantly increased the risk of drug discontinuation, whereas risankizumab was protective. Conclusion: In this multinational cohort with 8439 patient-years of follow-up, the cumulative probability of drug survival for all drugs was >79% at 18 months. Prescribed biologic, female sex, higher BMI, and previous exposure to biologic agents were predictors of drug discontinuation. Drug survival of guselkumab and risankizumab was higher than that of ustekinumab, and secukinumab was lower. [ABSTRACT FROM AUTHOR]

Purpose: Tizanidine, an alpha-adrenergic substance with antinociceptive and antihypertensive effects, is extensively metabolized via cytochrome P450 (CYP) 1A2. Therefore, coadministration with potent CYP1A2 inhibitors, such as ciprofloxacin, is contraindicated. However, both drugs are broadly utilized in various countries. Their concomitant use bears an inherent high risk for clinically significant symptoms, especially in multimorbid patients experiencing polypharmacy. This study aims to investigate the impact of coadministration of tizanidine and ciprofloxacin using real-world pharmacovigilance data and to raise awareness of this potentially underestimated safety issue. Methods: We conducted a retrospective study including Individual Case Safety Reports (ICSR) registered until March 1, 2017, in the World Health Organization (WHO) global database. Demographic data, drug administration information, the course of the adverse drug reaction (ADR), its severity, and outcomes were analyzed for cases reporting ciprofloxacin comedication. Results: In 91 (2.0%) of the identified 4192 worldwide ICSR on tizanidine, coadministration of ciprofloxacin was reported. Most of the patients were female (n = 59, 64.8%) with a median age of 54 years (range 13–85 years). The countries contributing most reports were the USA (n = 54, 59.3%) and Switzerland (n = 16, 17.6%). ADRs reported most often affected the nervous system and the cardiac function, especially with large tizanidine doses or drugs with CNS and cardiovascular depressant effects. In two cases, a fatal outcome was reported. Conclusion: Despite the existing formal contraindication, the concomitant use of tizanidine and ciprofloxacin can be observed in real-world clinical practice. Reactions mainly affected the central nervous and the cardiovascular system resulting in potentially severe adverse effects. The concomitant use of tizanidine and ciprofloxacin should absolutely be avoided. [ABSTRACT FROM AUTHOR]

Purpose: Increase in in situ breast cancer (BCIS) incidence has been reported across Europe and the USA. However, little is known about the trends in BCIS incidence in regions without population-based mammographic screening programs. We set out to investigate these trends in Zurich, Switzerland, where only opportunistic mammographic screening exists.Methods: Data from 989 women diagnosed with a primary BCIS between 2003 and 2014 were used in our analyses. Age-standardized incidence rates per 100,000 person-years (ASR) were computed per year. Additional analyses by BCIS subtype, by age group at diagnosis and by incidence period were conducted. Incidence trends over time were assessed using joinpoint regression analysis.Results: The overall BCIS ASR was 10.7 cases per 100,000 person-years with an increasing trend over the study period. A similar trend was observed for the ductal carcinoma in situ (DCIS) ASR, while the lobular carcinoma in situ (LCIS) ASR decreased. Age-specific analyses revealed that the 50-59 year age group had the highest BCIS ASR. The highest increase in BCIS ASR, even though not statistically significant, was observed for the < 40 year age group.Conclusions: BCIS ASR increased linearly over a 12-year period. The increase was reflected by an increase in DCIS ASR, whereas LCIS ASR decreased over time. The highest increase in BCIS ASR over the study period was observed for the < 40 year age group, even though not statistically significant. Patient and tumor characteristics of this group that may be associated with BCIS development warrant further investigation. [ABSTRACT FROM AUTHOR]

Public funding agencies largely support academic research as an effort to stimulate future product commercialization and foster broader societal benefits. Yet, translating research nurtured in academic settings into such outcomes is complex and demands functional interactions between government, academic, and industry, i.e., 'triple helix,' organizations within an innovation ecosystem. This article argues that in the spirit of responsible innovation, research funding should build bridges that extend beyond the triple helix stakeholders to connect to peripheral organizations. To support that argument, evidence from agent network analysis gathered from two case studies reveals strong and weak connections, as well as gaps within innovation ecosystems in Switzerland and metropolitan Phoenix, USA. This article offers insights on how innovation ecosystems are aligned or misaligned with responsible innovation. [ABSTRACT FROM AUTHOR]

The purpose of the study was to validate a recently proposed new grading system for ocular manifestations of chronic graft-versus-host disease (cGVHD). Diagnosis of cGVHD was based on the NIH consensus criteria. In addition, a grading scale was applied, which has been developed by the German-Austrian-Swiss Consensus Conference on Clinical Practice in cGVHD. Sixty-six patients (male n = 46, female n = 20, mean age 48 years) with ocular cGVHD were included. Application of the proposed Consensus Conference grading revealed inflammatory activity in all patients with mild (33 %), moderate (44 %), or severe inflammation (23 %). Clinical scoring by the NIH scoring system showed that 6 % of patients had mild symptoms; 59 % of patients had moderate dry eye symptoms partially affecting activities of daily living, without vision impairment; and 35 % of patients had severe dry eye symptoms significantly affecting daily activities. Clinical characterization and grading by the Consensus Conference grading scale revealed that ocular cGVHD (1) frequently leads to severe ocular surface disease based on impaired function of the lacrimal glands and involvement of cornea, conjunctiva, and lids; (2) is mostly associated with ongoing inflammatory activity; (3) often leads to functional impairment and reduced quality of life; and (4) is associated with an increased risk for severe, sight-threatening complications. [ABSTRACT FROM AUTHOR]

The diagnosis of medulloblastoma likely encompasses several distinct entities, with recent evidence for the existence of at least four unique molecular subgroups that exhibit distinct genetic, transcriptional, demographic, and clinical features. Assignment of molecular subgroup through routine profiling of high-quality RNA on expression microarrays is likely impractical in the clinical setting. The planning and execution of medulloblastoma clinical trials that stratify by subgroup, or which are targeted to a specific subgroup requires technologies that can be economically, rapidly, reliably, and reproducibly applied to formalin-fixed paraffin embedded (FFPE) specimens. In the current study, we have developed an assay that accurately measures the expression level of 22 medulloblastoma subgroup-specific signature genes (CodeSet) using nanoString nCounter Technology. Comparison of the nanoString assay with Affymetrix expression array data on a training series of 101 medulloblastomas of known subgroup demonstrated a high concordance (Pearson correlation r = 0.86). The assay was validated on a second set of 130 non-overlapping medulloblastomas of known subgroup, correctly assigning 98% (127/130) of tumors to the appropriate subgroup. Reproducibility was demonstrated by repeating the assay in three independent laboratories in Canada, the United States, and Switzerland. Finally, the nanoString assay could confidently predict subgroup in 88% of recent FFPE cases, of which 100% had accurate subgroup assignment. We present an assay based on nanoString technology that is capable of rapidly, reliably, and reproducibly assigning clinical FFPE medulloblastoma samples to their molecular subgroup, and which is highly suited for future medulloblastoma clinical trials. [ABSTRACT FROM AUTHOR]

An ombrotrophic peat core was collected in 2005 from Etang de la Gruère, Jura Mountains, Switzerland. The concentrations of nine among the U.S. Environmental Protection Agency priority polycyclic aromatic hydrocarbons (PAHs) (i.e., acenaphthene, phenanthrene, fluorene, pyrene, fluoranthene, benzo[ jbk]fluoranthene, benzo[ a]pyrene, benzo[ ghi]perylene, and indeno[1,2,3- cd]pyrene) were determined in both bulk peat and corresponding humic acids (HA) samples by gas chromatography equipped with a mass spectrometry detector (GC-MS). The maximum PAHs concentrations in peat (around 1,250 μg Σ PAHs kg−1 dry matter) were found at 28–30 cm of depth, which correspond to ca. 1920–1930, when coal inputs to Switzerland reached their maximum level. Amongst the nine PAHs analyzed in the peat samples, pyrene (Pyr) was the predominant species, accounting for ca. 20–100% of the total PAHs throughout the profile. In the HA fraction, that represents 24.7% (average value) of the bulk peat, only phenanthrene (Phe), and sporadically Pyr and fluoranthene (Fth), were detected. In particular, HA showed Phe concentrations that were ten–150 times higher than corresponding bulk peat samples, thus suggesting its preservation against biodegradation due to the incorporation into HA molecules. [ABSTRACT FROM AUTHOR]

The article covers issues related to pharmaceutical medicine as of August 2008. The U.S. Food and Drug Administration (FDA) has implemented changes to the labelling for prescription drugs as well as biological products. PricewaterhouseCoopers has regarded that the creation of a computer-simulated virtual man will help in pharmaceutical research and development. The 61st World Health Assembly held in Geneva, Switzerland has come up with a course of action to address the threats to global public health.

The baseline economic model for upper gastrointestinal (UGI) disease was developed in the context of patterns of care and resource use within the UK. It provided the opportunity to evaluate the extent to which an economic model developed in one country could be applied to meet the pharmacoeconomic information needs of decision makers in another. The choice of countries for analysis was restricted to countries within the International Gastro Primary Care Group (IGPCG) who had previously agreed on the appropriateness of the basic clinical algorithm to their domestic healthcare environment. This provided a potential sample of 9 countries (Australia, Austria, Germany, Italy, The Netherlands, Sweden, Switzerland, the UK and the USA) of which the UK, Germany, Sweden and Switzerland were chosen as providing a broad spectrum of strategic and operating environments in which to test the international transferability of the economic model. The process and results obtained provide valuable evidence of the extent to which economic analyses can be transferred across national borders. [ABSTRACT FROM AUTHOR]

The article focuses on the status of research on particle physics in the U.S. In the past, U.S. was the acknowledged leader in elementary-particle physics. But this was about to change when the Large Hadron Collider in Geneva, Switzerland starts its operation. The author suggests that the government must commit resources to bring the International Linear Collider to Fermilab to prevent the slow death of the laboratory and advance research on particle physics.

Information on the XXIII Indian Colloquium on Micropaleontology and Stratigraphy (ICMS) held during December 9-11, 2011 at the Department of Geology at the Bangalore University, Bangalore is presented. The ICMS Colloquia is held every two years at universities and national institutes across India. The conference has attracted 300 delegates from different colleges and universities across India and abroad including the U.S. and Switzerland.

Information about the World Health Organization (WHO) meeting held in Geneva, Switzerland is presented. Topics include the H5N1 avian influenza virus, a recommendation from the U.S. National Science Advisory Board for Biosecurity (NSABB) and the need for virus studies to be published in full. The meeting featured several notable people including Ron Fouchier, Yoshihiro Kawaoka and Paul Keim.

The article discusses the cancer drug DCVax-Brain and its approval process in Switzerland and the United States. The article describes how the Swiss Institute of Public Health declared that it would allow the importing and exporting of the drug even though it has not been approved. The United States Food and Drug Administration has delayed the development of the drug in order to ensure proper execution of clinical outcomes. Details are provided regarding the drug's use as a vaccine consisting in dendritic cells pulsed with antigens derived from a tumor cell lysate from a resected gioblastoma. Also discussed are the cancer drugs Provenge, Junovan, and MyVax.

The article presents the study conducted by Yanming Ma of Jilan University of China and colleagues from Switzerland, Germany, Russia, and the U.S. which found that sodium becomes transparent to visible light at pressures of about 200 gigapascals(GPa). It revealed that sodium will become back at 130 GPa and will become transparent at around 200 GPa. It concluded that there are other metals which are likely to show the same transparency under pressure.

The article reports that the race continues to discover the Higgs boson particle. Problems with a magnet have continued to delay the start of experiments using the Large Hadron Collider (LHC) particle accelerator near Geneva, Switzerland. The Tevatron collider at the Fermi National Accelerator Laboratory (Fermilab) in Illinois is also searching for the particle.

Reports on the completed sequencing of the rice genome by Switzerland-based agribusiness company, Syngenta Crop Protection Inc. in collaboration with Utah-based company, Myriad Genetics Inc. Deals between the two companies for sequencing of the rice genome; Plans of Syngenta regarding the publication of data on sequencing of the rice genome.

Reports on the departure of Basel, Switzerland-based Novartis Pharmaceuticals Inc. from its partnership with Carlsbad, California-based Isis Pharmaceuticals Inc. Changes in the financing arrangement made by Isis; Impact of development of two antisense compounds by Isis; Applications of the antisense technology.

Discusses a bill backing the involvement of the United States in the construction of Europe's planned Large Hadron Collider. Endorsement of budget for high-energy physics; Direction of United States Energy Secretary Hazel O'Leary to negotiate with the European Laboratory for Particle Physics; Conditions set for any resultant agreement.

Reports on American government policy regarding the Large Hadron Collider (LHC) at the European Laboratory for Particle Physics (CERN) in Geneva, Switzerland. Failure of science adviser John Gibbons to back the idea in a presentation to Congress; Cancellation of the Superconducting Super Collider (SSC); Estimated cost of participation in CERN.

Reports on the dispute between Carlo Rubbia, the director of the European Laboratory for Participle Physics (CERN) and researchers at the Los Alamos National Laboratory in the United States over competing claims regarding a technique in producing nuclear energy. Claim of the group from Los Alamos that they described Rubbia's concept in detail in a paper published 1992.

Reports that United States and European officials have signed an agreement under which the US will contribute funds towards the construction of the Large Hadron Collider, European Laboratory for Particle Physics (CERN), Geneva, Switzerland. Comments from US energy secretary Federico Pena; Details of US contribution; Project's completion date.

Discusses United States Representative James Sensenbrenner's acceptance of a modified agreement for United States participation in the Large Hadron Collider (LHC) project. The responsibility of Sensenbrenner as the chairman of the Science Committee in the US House of Representatives; The LHC being part of the European Laboratory for Particle Physics (CERN); The negotiations between CERN and the US Department of Energy; The objections of some US lawmakers against American involvement.

Editorial. Discusses the debate in the US Congress over whether funds will be given for participation in the Large Hadron Collider (LHC) at the European Laboratory for Particle Physics (CERN). The campaign of Joe Barton of Texas against US support; The decision by the Science Committee of the House of Representative to withhold funding pending clarifications from the US Department of Energy.

Reports on the decision by the Clinton administration to back a United States contribution towards construction of the Large Hadron Collider (LHC) at the European particle physics laboratory (CERN) in Geneva, Switzerland. The efforts of the Department of Energy; The findings of the White House Office of Management and Budget; The impact of the United States decision.