The Association of Race, Rurality, and Neighborhood Disadvantage with Disease Severity at Initial Presentation in Cervical Spondylotic Myelopathy: A Cohort Study.

Study Design: Retrospective Cohort Study.

Objectives: To examine the impact of neighborhood-level socioeconomic factors on the delay of care and severity of disease among DCM patients at initial presentation.

Summary Of Background Data: Degenerative Cervical Myelopathy (DCM) is the most common etiology for spinal cord dysfunction among adults worldwide.

Revisiting the Last Ice Area projections from a high-resolution Global Earth System Model.

The Last Ice Area-located to the north of Greenland and the northern Canadian Arctic Archipelago-is expected to persist as the central Arctic Ocean becomes seasonally ice-free within a few decades. Projections of the Last Ice Area, however, have come from relatively low resolution Global Climate Models that do not resolve sea ice export through the waterways of the Canadian Arctic Archipelago and Nares Strait. Here we revisit Last Ice Area projections using high-resolution numerical simulations from the Community Earth System Model, which resolves these narrow waterways.

Development of a Second-Generation, Chemical Probe for PIKfyve.

We optimized our highly potent and cell-active chemical probe for phosphatidylinositol-3-phosphate 5-kinase (PIKfyve), SGC-PIKFYVE-1, resulting in compounds with improved potency and demonstrated stability. Use of an in-cell, kinome-wide selectivity panel allowed for confirmation of excellent in-cell selectivity of our lead compound, , and another promising analogue, . Evaluation of the pharmacokinetic (PK) profiles of these two compounds revealed that both are well tolerated systemically and orally bioavailable.

Diagnostic features of functional/ dissociative seizures in the first presentation of transient loss of consciousness.

Objectives: Previous studies have identified features in patient's history and seizure descriptions supporting a clinical diagnosis of functional / dissociative seizures (FDS). However, most studies involved patients with chronic seizure disorders. This study explores the value of reported features for a clinical diagnosis of FDS in an adult population with a first presentation of transient loss of consciousness (TLoC).

Targeting Oestrogen Receptor Signalling in Breast Cancer Therapy.

There has been over 130 years of research into the treatment of breast cancer using approaches that target oestrogen receptor signalling. Here, we summarise the development of the key pillars of such endocrine therapy, namely, oestrogen deprivation, achieved through ovarian suppression and/or aromatase inhibition, and oestrogen receptor blockade, through selective oestrogen receptor modulators, downregulators and novel compounds entering early phase development. The translation of these compounds from advanced to early breast cancer settings is discussed with a focus on the placebo-controlled breast cancer prevention studies to most accurately describe the side effect profiles of the main approaches.