Studying kinetochore kinases

Mitotic kinetochores are signaling network hubs that regulate chromosome movements, attachment error-correction, and the spindle assembly checkpoint. Key switches in these networks are kinases and phosphatases that enable rapid responses to changing conditions. Describing the mechanisms and dynamics of their localized activation and deactivation is therefore instrumental for understanding the spatiotemporal control of chromosome segregation

CONSORT Harms 2022 statement, explanation, and elaboration: updated guideline for the reporting of harms in randomized trials.

Randomized controlled trials remain the reference standard for healthcare research on effects of interventions, and the need to report both benefits and harms is essential. The Consolidated Standards of Reporting Trials (the main CONSORT) statement includes one item on reporting harms (i.e., all important harms or unintended effects in each group). In 2004, the CONSORT group developed the CONSORT Harms extension; however, it has not been consistently applied and needs to be updated. Here, we describe CONSORT Harms 2022, which replaces the CONSORT Harms 2004 checklist, and shows how CONSORT Harms 2022 items could be incorporated into the main CONSORT checklist. Thirteen items from the main CONSORT were modified to improve harms reporting. Three new items were added. In this article, we describe CONSORT Harms 2022 and how it was integrated into the main CONSORT checklist and elaborate on each item relevant to complete reporting of harms in randomized controlled trials. Until future work from the CONSORT group produces an updated checklist, authors, journal reviewers, and editors of randomized controlled trials should use the integrated checklist presented in this paper

Intramedullary melanotic schwannoma

We present a case of an intramedullary melanotic schwannoma (IMS) of the thoracic spinal cord. To our knowledge, this is the seventh reported case of an IMS of the central nervous system. Schwannomas are benign nerve sheath tumors of neural crest origin composed entirely of well differentiated Schwann cells that typically occur in peripheral nerves. Both the intramedullary location and the melanotic component of the reported lesion make it exceedingly rare. We will present our case, theories as to the origin of these tumors, clues in radiographic identification, and current clinical follow-up recommendations

Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis

The mitotic checkpoint prevents mitotic exit until all chromosomes are attached to spindle microtubules. Aurora B kinase indirectly invokes this checkpoint by destabilizing incorrect attachments; however, a more direct role remains controversial. In contrast, activity of the kinase Mps1 is indispensible for the mitotic checkpoint. Here we show that Aurora B and Hec1 are needed for efficient Mps1 recruitment to unattached kinetochores, allowing rapid Mps1 activation at the onset of mitosis. Live monitoring of cyclin B degradation reveals that this is essential to establish the mitotic checkpoint quickly at the start of mitosis. Delayed Mps1 activation and checkpoint establishment upon Aurora B inhibition or Hec1 depletion are rescued by tethering Mps1 to kinetochores, demonstrating that Mps1 recruitment is the primary role of Aurora B and Hec1 in mitotic checkpoint signalling. These data demonstrate a direct role for Aurora B in initiating the mitotic checkpoint rapidly at the onset of mitosis

CONSORT Harms 2022 statement, explanation, and elaboration: updated guideline for the reporting of harms in randomised trials

Randomised controlled trials remain the reference standard for healthcare research on effects of interventions, and the need to report both benefits and harms is essential. The Consolidated Standards of Reporting Trials (the main CONSORT) statement includes one item on reporting harms (ie, all important harms or unintended effects in each group). In 2004, the CONSORT group developed the CONSORT Harms extension; however, it has not been consistently applied and needs to be updated. Here, we describe CONSORT Harms 2022, which replaces the CONSORT Harms 2004 checklist, and shows how CONSORT Harms 2022 items could be incorporated into the main CONSORT checklist. Thirteen items from the main CONSORT were modified to improve harms reporting. Three new items were added. In this article, we describe CONSORT Harms 2022 and how it was integrated into the main CONSORT checklist, and elaborate on each item relevant to complete reporting of harms in randomised controlled trials. Until future work from the CONSORT group produces an updated checklist, authors, journal reviewers, and editors of randomised controlled trials should use the integrated checklist presented in this paper

Chapter 8: Meta-analysis of Test Performance When There is a “Gold Standard”

Synthesizing information on test performance metrics such as sensitivity, specificity, predictive values and likelihood ratios is often an important part of a systematic review of a medical test. Because many metrics of test performance are of interest, the meta-analysis of medical tests is more complex than the meta-analysis of interventions or associations. Sometimes, a helpful way to summarize medical test studies is to provide a “summary point”, a summary sensitivity and a summary specificity. Other times, when the sensitivity or specificity estimates vary widely or when the test threshold varies, it is more helpful to synthesize data using a “summary line” that describes how the average sensitivity changes with the average specificity. Choosing the most helpful summary is subjective, and in some cases both summaries provide meaningful and complementary information. Because sensitivity and specificity are not independent across studies, the meta-analysis of medical tests is fundamentaly a multivariate problem, and should be addressed with multivariate methods. More complex analyses are needed if studies report results at multiple thresholds for positive tests. At the same time, quantitative analyses are used to explore and explain any observed dissimilarity (heterogeneity) in the results of the examined studies. This can be performed in the context of proper (multivariate) meta-regressions

CONSORT Harms 2022 statement, explanation, and elaboration: updated guideline for the reporting of harms in randomised trials

Randomised controlled trials remain the reference standard for healthcare research on effects of interventions, and the need to report both benefits and harms is essential. The Consolidated Standards of Reporting Trials (the main CONSORT) statement includes one item on reporting harms (ie, all important harms or unintended effects in each group). In 2004, the CONSORT group developed the CONSORT Harms extension; however, it has not been consistently applied and needs to be updated. Here, we describe CONSORT Harms 2022, which replaces the CONSORT Harms 2004 checklist, and shows how CONSORT Harms 2022 items could be incorporated into the main CONSORT checklist. Thirteen items from the main CONSORT were modified to improve harms reporting. Three new items were added. In this article, we describe CONSORT Harms 2022 and how it was integrated into the main CONSORT checklist, and elaborate on each item relevant to complete reporting of harms in randomised controlled trials. Until future work from the CONSORT group produces an updated checklist, authors, journal reviewers, and editors of randomised controlled trials should use the integrated checklist presented in this paper