Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL.

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype

Cross-Sectional Exploration of Plasma Biomarkers of Alzheimer's Disease in Down Syndrome: Early Data from the Longitudinal Investigation for Enhancing Down Syndrome Research (LIFE-DSR) Study

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer's disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ1-40, Aβ1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology

Contrasting size and fate of juvenile crown-of-thorns starfish linked to ontogenetic diet shifts

Population dynamics of organisms are shaped by the variation in phenotypic traits, often expressed even among individuals from the same cohort. For example, individual variation in the timing of ontogenetic shifts in diet and/or habitat greatly influences subsequent growth and survival of some organisms, with critical effects on population dynamics. Few studies of natural systems have, however, demonstrated that marked phenotypic variation in growth rates or body size among individuals within a modelled cohort is linked to dietary shifts and food availability. Population irruptions of the crown-of-thorns starfish are one of the foremost contributors to the global degradation of coral reefs, but causes of irruptions have been debated for decades. Here we demonstrate, based on extensive field sampling of juvenile starfish (n = 3532), that marked variation in body size among juvenile starfish is linked to an ontogenetic diet shift from coralline algae to coral. This transition in diet leads to exponential growth in juveniles and is essential for individuals to reach maturity. Because smaller individuals experience higher mortality and growth is stunted on an algal diet, the ontogenetic shift to corallivory enhances individual fitness and replenishment success. Our findings suggest that the availability of coral prey facilitates early ontogenetic diet shifts and may be fundamental in initiating population irruptions

Incidence and severity of injuries among juvenile crown-of-thorns starfish on Australia's Great Barrier Reef

Outbreaks of crown-of-thorns starfish (Acan- thaster spp.) represent a major threat to coral reef ecosystems throughout the Indo-Pacific, and there is sig- nificant interest in whether no-take marine reserves could moderate the frequency or severity of outbreaks. Herein, we investigate whether the incidence and severity of sub- lethal injuries among juvenile Pacific crown-of-thorns starfish (Acanthaster cf. solaris, max diameter = 45 mm) differs between areas that are open versus closed to fishing, between microhabitats (i.e. dead coral substratum versus live coral) and with body size. The majority (180 out of 200) of juvenile starfish had conspicuous injuries, pre- sumably caused by predation. The incidence of injuries in juvenile starfish was negatively related to body size, but links between body size and severity of injuries were only evident in individuals collected from dead coral micro- habitats. Small (3 mm radius) starfish from dead coral microhabitats had injuries to 68.06% of arms, compared to 12.00% of arms in larger (12 mm radius) starfish from the same microhabitat. Juvenile starfish associated with dead coral habitats had a higher incidence (95 vs. 87% respec- tively) and severity (i.e. the percentage of injured arms; 21 vs. 6%) of injuries, compared to those associated with live corals. Interestingly, there was no difference in the inci- dence or severity of injuries between areas that are open versus closed to fishing. Our results show that small juvenile A. cf. solaris are extremely vulnerable to sublethal, if not lethal, predation, and predation risk declines as they grow and change their microhabitat. Pre- dation during and immediately following settlement is, therefore, likely to have a major influence on population dynamics and ontogenetic changes in microhabitat use for A. cf. solaris

Habitat associations of settlement-stage crown-of-thorns starfish on Australia’s Great Barrier Reef

Population irruptions of crown-of-thorns starfish (Acanthaster spp.) contribute greatly to the degradation of coral reefs throughout the Indo-Pacific. Effective management of these population irruptions is limited, in part, by incomplete knowledge of their early life history. Importantly, there are very limited data on the distribution and abundance of newly settled crown-of-thorns starfish (0+ starfish, in their first year since settlement). Extensive sampling was conducted around the circumference of three distinct mid-shelf reefs (at 1–18 m depths) in the central Great Barrier Reef (GBR), during active population irruptions, in May–June 2017, to quantify the occurrence and densities of settlement-stage starfish (2–65 mm diameter) and relate patterns of abundance to distinct habitat features at the scale of individual reefs. Overall, 140 settlement-stage starfish were detected across 1242 quadrats (1 m2). Settlement-stage starfish were recorded from 31 out of 42 sites (73.8%) at mean densities of 0–0.77 starfish m-2. Both estimated densities and the likelihood of occurrence of settlement-stage starfish within quadrats increased overall with the proportion of coral rubble (and dead intact corals), were greatest at intermediate depths (8–14 m), but decreased with the proportion of live hard coral. At the scale of individual reefs, settlement-stage starfish occurred most frequently in south-western and northern fore reef habitats. Our results suggest that settlement and/or early post-settlement survival of crown-ofthorns starfish is greatest in relatively shallow waters of obliquely exposed fore reef habitats where there is high cover of coral rubble. The specific occurrence of these habitat types (within spur and groove systems and rubble slips) provides an opportunity to concentrate searches and increase effective sampling of settlement-stage starfish, though these habitats are relatively widespread and unlikely to constrain the population replenishment or population irruptions of crown-of-thorns starfish on the GBR