Closing in on the Cosmos: Cosmology's Rebirth and the Rise of the Dark Matter Problem

Influenced by the renaissance of general relativity that came to pass in the 1950s, the character of cosmology fundamentally changed in the 1960s as it became a well-established empirical science. Although observations went to dominate its practice, extra-theoretical beliefs and principles reminiscent of methodological debates in the 1950s kept playing an important tacit role in cosmological considerations. Specifically, belief in cosmologies that modeled a "closed universe" based on Machian insights remained influential. The rise of the dark matter problem in the early 1970s serves to illustrate this hybrid methodological character of cosmological science

How Dark Matter Came to Matter

The history of the dark matter problem can be traced back to at least the 1930s, but it was not until the early 1970s that the issue of 'missing matter' was widely recognized as problematic. In the latter period, previously separate issues involving missing mass were brought together in a single anomaly. We argue that reference to a straightforward 'accumulation of evidence' alone is inadequate to comprehend this episode. Rather, the rise of cosmological research, the accompanying renewed interest in the theory of relativity and changes in the manpower division of astronomy in the 1960s are key to understanding how dark matter came to matter. At the same time, this story may also enlighten us on the methodological dimensions of past practices of physics and cosmology.Comment: Accepted for publication in Nature Astronomy. Corrected typ

Closing in on the Cosmos: Cosmology's Rebirth and the Rise of the Dark Matter Problem

Influenced by the renaissance of general relativity that came to pass in the 1950s, the character of cosmology fundamentally changed in the 1960s as it became a well-established empirical science. Although observations went to dominate its practice, extra-theoretical beliefs and principles reminiscent of methodological debates in the 1950s kept playing an important tacit role in cosmological considerations. Specifically, belief in cosmologies that modeled a “closed universe” based on Machian insights remained influential. The rise of the dark matter problem in the early 1970s serves to illustrate this hybrid methodological character of cosmological science

Closing in on the Cosmos: Cosmology's Rebirth and the Rise of the Dark Matter Problem

Influenced by the renaissance of general relativity that came to pass in the 1950s, the character of cosmology fundamentally changed in the 1960s as it became a well-established empirical science. Although observations went to dominate its practice, extra-theoretical beliefs and principles reminiscent of methodological debates in the 1950s kept playing an important tacit role in cosmological considerations. Specifically, belief in cosmologies that modeled a "closed universe" based on Machian insights remained influential. The rise of the dark matter problem in the early 1970s serves to illustrate this hybrid methodological character of cosmological science

Test, trace, isolate:Evidence for declining SARS-CoV-2 PCR sensitivity in a clinical cohort

Real-time reverse transcription-polymerase chain reaction (RT-PCR) on upper respiratory tract (URT) samples is the primary method to diagnose SARS-CoV-2 infections and guide public health measures, with a supportive role for serology. We reinforce previous findings on limited sensitivity of PCR testing, and solidify this fact by statistically utilizing a firm basis of multiple tests per individual. We integrate stratifications with respect to several patient characteristics such as severity of disease and time since onset of symptoms. Bayesian statistical modelling was used to retrospectively determine the sensitivity of RT-PCR using SARS-CoV-2 serology in 644 COVID-19-suspected patients with varying degrees of disease severity and duration. The sensitivity of RT-PCR ranged between 80% − 95%; increasing with disease severity, it decreased rapidly over time in mild COVID-19 cases. Negative URT RT-PCR results should be interpreted in the context of clinical characteristics, especially with regard to containment of viral transmission based on ‘test, trace and isolate’

High quality of SARS-CoV-2 molecular diagnostics in a diverse laboratory landscape through supported benchmark testing and External Quality Assessment

A two-step strategy combining assisted benchmark testing (entry controls) and External Quality Assessments (EQAs) with blinded simulated clinical specimens to enhance and maintain the quality of nucleic acid amplification testing was developed. This strategy was successfully applied to 71 diagnostic laboratories in The Netherlands when upscaling the national diagnostic capacity during the SARS-CoV-2 pandemic. The availability of benchmark testing in combination with advice for improvement substantially enhanced the quality of the laboratory testing procedures for SARS-CoV-2 detection. The three subsequent EQA rounds demonstrated high quality testing with regard to specificity (99.6% correctly identified) and sensitivity (93.3% correctly identified). Even with the implementation of novel assays, changing workflows using diverse equipment and a high degree of assay heterogeneity, the overall high quality was maintained using this two-step strategy. We show that in contrast to the limited value of Cq value for absolute proxies of viral load, these Cq values can, in combination with metadata on strategies and techniques, provide valuable information for laboratories to improve their procedures. In conclusion, our two-step strategy (preparation phase followed by a series of EQAs) is a rapid and flexible system capable of scaling, improving, and maintaining high quality diagnostics even in a rapidly evolving (e.g. pandemic) situation.</p

High quality of SARS-CoV-2 molecular diagnostics in a diverse laboratory landscape through supported benchmark testing and External Quality Assessment

A two-step strategy combining assisted benchmark testing (entry controls) and External Quality Assessments (EQAs) with blinded simulated clinical specimens to enhance and maintain the quality of nucleic acid amplification testing was developed. This strategy was successfully applied to 71 diagnostic laboratories in The Netherlands when upscaling the national diagnostic capacity during the SARS-CoV-2 pandemic. The availability of benchmark testing in combination with advice for improvement substantially enhanced the quality of the laboratory testing procedures for SARS-CoV-2 detection. The three subsequent EQA rounds demonstrated high quality testing with regard to specificity (99.6% correctly identified) and sensitivity (93.3% correctly identified). Even with the implementation of novel assays, changing workflows using diverse equipment and a high degree of assay heterogeneity, the overall high quality was maintained using this two-step strategy. We show that in contrast to the limited value of Cq value for absolute proxies of viral load, these Cq values can, in combination with metadata on strategies and techniques, provide valuable information for laboratories to improve their procedures. In conclusion, our two-step strategy (preparation phase followed by a series of EQAs) is a rapid and flexible system capable of scaling, improving, and maintaining high quality diagnostics even in a rapidly evolving (e.g. pandemic) situation.</p

Deciphering dark matter: the remarkable life of Fritz Zwicky

Jaco de Swart enjoys a biography of the scientist who pioneered findings on dark matter and supernovae

Test, trace, isolate: Evidence for declining SARS-CoV-2 PCR sensitivity in a clinical cohort

Real-time reverse transcription-polymerase chain reaction (RT-PCR) on upper respiratory tract (URT) samples is the primary method to diagnose SARS-CoV-2 infections and guide public health measures, with a supportive role for serology. We reinforce previous findings on limited sensitivity of PCR testing, and solidify this fact by statistically utilizing a firm basis of multiple tests per individual. We integrate stratifications with respect to several patient characteristics such as severity of disease and time since onset of symptoms. Bayesian statistical modelling was used to retrospectively determine the sensitivity of RT-PCR using SARS-CoV-2 serology in 644 COVID-19-suspected patients with varying degrees of disease severity and duration. The sensitivity of RT-PCR ranged between 80% − 95%; increasing with disease severity, it decreased rapidly over time in mild COVID-19 cases. Negative URT RT-PCR results should be interpreted in the context of clinical characteristics, especially with regard to containment of viral transmission based on ‘test, trace and isolate’