Real-World Palbociclib Use in HR+/HER2− Advanced Breast Cancer in Canada: The IRIS Study

Background: Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor used in combination with aromatase inhibitors or fulvestrant for patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). Palbociclib was the first CDK 4/6 inhibitor approved for HR+/HER2− ABC/MBC treatment in Canada in combination with letrozole (P+L) as an initial endocrine-based therapy (approved March 2016), or with fulvestrant (P+F) following disease progression after prior endocrine therapy (approved May 2017). The Ibrance Real World Insights (IRIS) study ({"type":"clinical-trial","attrs":{"text":"NCT03159195","term_id":"NCT03159195"}}NCT03159195) collected real-world outcomes data for palbociclib-treated patients in several countries, including Canada. Methods: This retrospective chart review included women with HR+/HER2− ABC/MBC receiving P+L or P+F in Canada. Physicians reviewed medical records for up to 14 patients, abstracting demographic and clinical characteristics, treatment patterns, and clinical outcomes. Progression-free rates (PFRs) and survival rates (SRs) at 6, 12, 18, and 24 months were estimated via Kaplan–Meier analysis. Results: Thirty-three physicians examined medical records for 247 patients (P+L, n = 214; P+F, n = 33). Median follow-up was 8.8 months for P+L and 7.0 months for P+F. Most patients were initiated on palbociclib 125 mg/d (P+L, 90.2%; P+F, 84.8%). Doses were reduced in 16.6% of P+L and 14.3% of P+F patients initiating palbociclib at 125 mg/d. The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%. Conclusions: Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective.     

A Review of Machine Learning Techniques for Keratoconus Detection and Refractive Surgery Screening

ABSTRACT

Various machine learning techniques have been developed for keratoconus detection and refractive surgery screening. These techniques utilize inputs from a range of corneal imaging devices and are built with automated decision trees, support vector machines, and various types of neural networks. In general, these techniques demonstrate very good differentiation of normal and keratoconic eyes, as well as good differentiation of normal and form fruste keratoconus. However, it is difficult to directly compare these studies, as keratoconus represents a wide spectrum of disease. More importantly, no public dataset exists for research purposes. Despite these challenges, machine learning in keratoconus detection and refractive surgery screening is a burgeoning field of study, with significant potential for continued advancement as imaging devices and techniques become more sophisticated.     

Challenges for Research into Military Investigations

In cases of suspected violations of rules, regulations or the law by armed forces personnel, investigations are invariably mandatory. Military investigations differ from well-researched civilian criminal investigations. Differing from civilian police detectives, most military investigators – as disciplinary supervisors and military police personnel – have a number of tasks to accomplish, which include leading in combat and ensuring military readiness. Military investigations can lead to substantive negative or positive consequences for military readiness, including mental health, unit cohesion and subjective legal certainty. This impact on unit cohesion and mental health is influenced by any prior history of distress or trauma; military investigations are often preceded by contravention of internal disciplinary acts, complaints and traumatic events. This study explores factors in the differing military and legal systems of Germany and the United Kingdom (UK) that might help military personnel to successfully conduct investigations while ensuring deployment readiness and maintaining human rights.     

Sperm fishing: antigen-antibody complexes for the capture and enrichment of spermatozoa in mixed cell substrates

ABSTRACT

In many sexual assault cases, the most common evidence gathered comes in the form of intimate swabs. These swabs contain cells from both the female and male. In these cases the most common cell present is epithelial cells from the female with relatively few spermatozoa from the male. To produce an STR DNA profile suitable for an investigation, separation of the cell types is required to prevent a mixed profile that may complicate interpretation. While there are methods that can achieve this separation, they are labour intensive and have no guarantee of complete separation of the spermatozoa. Immunomagnetic bead separation techniques are being adapted from other scientific fields to be used in forensic biology to separate spermatozoa from mixed substrates. This study tested the binding of a Hyaluronidase PH-20 (SPAM1) antibody to spermatozoa in mixed cell samples that have been dried and stored for a short period of time. Fluorescently tagged antibodies were incubated with cellular mixtures and visualized using fluorescent microscopy. Successful binding of the antibodies to spermatozoa was observed in all samples. The SPAM1 antibody appears to be suitable for selection of spermatozoa and creates opportunities for linking with magnetic beads facilitate cell separation and DNA profiling.     

The size-weight illusion in visual form agnosic patient DF

ABSTRACT

The size-weight illusion is a perceptual illusion where smaller objects are judged as heavier than equally weighted larger objects. A previous informal report suggests that visual form agnosic patient DF does not experience the size-weight illusion when vision is the only available cue to object size. We tested this experimentally, comparing the magnitudes of DF’s visual, kinesthetic and visual-kinesthetic size-weight illusions to those of 28 similarly-aged controls. A modified t-test found that DF’s visual size-weight illusion was significantly smaller than that of controls (z_cc = ?1.7). A test of simple dissociation based on the Revised Standardized Difference Test found that the discrepancy between the magnitude of DF’s visual and kinesthetic size-weight illusions was not significantly different from that of controls (z_dcc = ?1.054), thereby failing to establish a dissociation between the visual and kinesthetic conditions. These results are consistent with previous suggestions that visual form agnosia, following ventral visual stream damage, is associated with an abnormally reduced size-weight illusion. The results, however, do not confirm that this reduction is specific to the use of visual size cues to predict object weight, rather than reflecting more general changes in the processing of object size cues or in the use of predictive strategies for lifting.