Improving biomarker assessment in breast pathology

The accuracy of prognostic and therapy-predictive biomarker assessment in breast tumours is crucial for management and therapy decision in patients with breast cancer. In this thesis, biomarkers used in clinical practice with emphasise on Ki67 and HER2 were studied using several methods including immunocytochemistry, in situ hybridisation, gene expression assays and digital image analysis, with the overall aim to improve routine biomarker evaluation and clarify the prognostic potential in early breast cancer. In paper I, we reported discordances in biomarker status from aspiration cytology and paired surgical specimens from breast tumours. The limited prognostic potential of immunocytochemistry-based Ki67 scoring demonstrated that immunohistochemistry on resected specimens is the superior method for Ki67 evaluation. In addition, neither of the methods were sufficient to predict molecular subtype. Following this in paper II, biomarker agreement between core needle biopsies and subsequent specimens was investigated, both in the adjuvant and neoadjuvant setting. Discordances in Ki67 and HER2 status between core biopsies and paired specimens suggested that these biomarkers should be re-tested on all surgical breast cancer specimens. In paper III, digital image analysis using a virtual double staining software was used to compare methods for assessment of proliferative activity, including mitotic counts, Ki67 and the alternative marker PHH3, in different tumour regions (hot spot, invasive edge and whole section). Digital image analysis using virtual double staining of hot spot Ki67 outperformed the alternative markers of proliferation, especially in discriminating luminal B from luminal A tumours. Replacing mitosis in histological grade with hot spot-scored Ki67 added significant prognostic information. Following these findings, the optimal definition of a hot spot for Ki67 scoring using virtual double staining in relation to molecular subtype and outcome was investigated in paper IV. With the growing evidence of global scoring as a superior method to improve reproducibility of Ki67 scoring, a different digital image analysis software (QuPath) was also used for comparison. Altogether, we found that automated global scoring of Ki67 using QuPath had independent prognostic potential compared to even the best virtual double staining hot spot algorithm, and is also a practical method for routine Ki67 scoring in breast pathology. In paper V, the clinical value of HER2 status was investigated in a unique trastuzumab-treated HER2-positive cohort, on the protein, mRNA and DNA levels. The results demonstrated that low levels of ERBB2 mRNA but neither HER2 copy numbers, HER2 ratio nor ER status, was associated with risk of recurrence among anti-HER2 treated breast cancer patients. In conclusion, we have identified important clinical aspects of Ki67 and HER2 evaluation and provided methods to improve the prognostic potential of Ki67 using digital image analysis. In addition to protein expression of routine biomarkers, mRNA levels by targeted gene expression assays may add further prognostic value in early breast cance

Exciton resonances quench the photoluminescence of zigzag carbon nanotubes

We show that the photoluminescence intensity of single-walled carbon nanotubes is much stronger in tubes with large chiral angles - armchair tubes - because exciton resonances make the luminescence of zigzag tubes intrinsically weak. This exciton-exciton resonance depends on the electronic structure of the tubes and is found more often in nanotubes of the +1 family. Armchair tubes do not necessarily grow preferentially with present growth techniques; they just have stronger luminescence. Our analysis allows to normalize photoluminescence intensities and find the abundance of nanotube chiralities in macroscopic samples.Comment: 4 pages and 2 supplementary pages; 6 figure

Share Your Perspective: ADHD in Our Libraries and Profession

Presentation slidesADDitude Magazine (n.d.), geared toward individuals with ADHD, rated librarianship as the 5th worst job out of 10 for those with “restless minds and creative spirits.” While some may agree that a profession which traditionally valued quiet and “keeping every Dewey Decimal in its proper place” might not be the best for neurodivergent folks struggling with inattentiveness, others see the structure and dynamic nature of librarianship as an ideal setting. National Resource Center, Children and Adults with Attention-Deficit/Hyperactivity Disorder (CHADD), list distractibility, impulsivity, hyperactivity, poor memory, boredom-blockouts, time management difficulties, procrastination, difficulty managing long-term projects, paperwork/details, and interpersonal/social skill issues being the top workplace issues for adults with ADHD but also offer specific tips to address each issue. In this facilitated discussion, we will discuss ADHD our libraries and/or as librarians with care to not disclose personal information that is not our own, and even then, only at the discretion of each participant with no disclosure preferred over participant comfort. By the end of the discussion, participants will walk away with a better understanding of how to help themselves or co-workers and patrons with ADHD

Computer-Based Cognitive Retraining for Adults with Chronic Acquired Brain Injury: A Pilot Study

This study evaluated the effectiveness of a computer-based cognitive retraining (CBCR) program on improving memory and attention deficits in individuals with a chronic acquired brain injury (ABI). Twelve adults with a chronic ABI demonstrating deficits in memory and attention were recruited from a convenience sample from the community. Using a quasi-experimental one-group pretest–posttest design, a significant improvement was found in both memory and attention scores postintervention using the cognitive screening tool. This study supported the effectiveness of CBCR programs in improving cognitive deficits in memory and attention in individuals with chronic ABI. Further research is recommended to validate these findings with a larger ABI population and to investigate transfer to improvement in occupational performance that supports daily living skills

BIOMECHANICS OF GOAL-KICKING ACCURACY IN AUSTRALIAN FOOTBALL USING AN INERTIAL MEASUREMENT SYSTEM

Accurate goal-kicking is important to a team’s success in Australian Football (AF). However, it remains a largely unexplored area in sport biomechanics. This study examined technical aspects of goal-kicking accuracy using an inertial measurement system (IMS). Two junior AF players performed 15x20m goal-kicks in the field. Kinematics were measured using the Xsens MVN link IMS (240Hz). Results showed that both players had greater support leg (p\u3c0.04; d\u3e1.0) and kick leg (d\u3e1.0) knee flexion during accurate goal-kicks. Individual differences were reported for footspeed and shank angular velocities for accurate goal-kicks. These individual differences highlight the need to conduct an individual-based analysis in goal-kicking research

Are hygiene standards useful in assessing infection risk?

We monitored the surface level cleanliness of a five-bedded surgical intensive care unit (SICU) over a ten-week period in order to evaluate proposed hygiene standards.Ten environmental sites within SICU were sampled twice weekly along with collection of clinical and patient activity data. The standards designate aerobic colony counts (ACCs) >2.5cfu/cm2 from hand-touch sites and the presence of Staphylococcus aureus as hygiene failures. Nearly a quarter of 200 samples failed the standards, mostly from hand-touch sites on curtains, beds and medical equipment. The total number of fails each week was associated with bed occupancy (p=0.04), trending towards association with SICU-acquired infections (p=0.11). Environmental S.aureus was associated with the proportion of beds occupied (p = 0.02). Indistinguishable genotypes were found between patient and environmental staphylococci, with timescales supporting staphylococcal transmission in both directions. Hygiene standards based on microbial growth levels and the presence of S.aureus reflect patient activity and provide a means to risk manage infection. They also exposed a staphylococcal reservoir that could represent a more tangible risk to patients. Standards for surface level cleanliness deserve further evaluation