Test–retest Reliability and Minimal Detectable Change of Corticospinal Tract Integrity in Chronic Stroke

Diffusion tensor imaging (DTI) can be used to index white matter integrity of the corticospinal tract (CST) after stroke; however, the psychometric properties of DTI‐based measures of white matter integrity are unknown. The purpose of this study was to examine test–retest reliability as determined by intraclass correlation coefficients (ICC) and calculate minimal detectable change (MDC) of DTI‐based measures of CST integrity using three different approaches: a Cerebral Peduncle approach, a Probabilistic Tract approach, and a Tract Template approach. Eighteen participants with chronic stroke underwent DTI on the same magnetic resonance imaging scanner 4 days apart. For the Cerebral Peduncle approach, a researcher hand drew masks at the cerebral peduncle. For the Probabilistic Tract approach, tractography was seeded in motor areas of the cortex to the cerebral peduncle. For the Tract Template approach, a standard CST template was transformed into native space. For all approaches, the researcher performing analyses was blind to participant number and day of data collection. All three approaches had good to excellent test–retest reliability for fractional anisotropy (FA; ICCs \u3e0.786). Mean diffusivity, axial diffusivity, and radial diffusivity were less reliable than FA. The ICC values were highest and MDC values were the smallest for the most automated approach (Tract Template), followed by the combined manual/automated approach (Probabilistic Tract) then the manual approach (Cerebral Peduncle). The results of this study may have implications for how DTI‐based measures of CST integrity are used to define impairment, predict outcomes, and interpret change after stroke

Test–retest reliability and minimal detectable change of corticospinal tract integrity in chronic stroke

Diffusion tensor imaging (DTI) can be used to index white matter integrity of the corticospinal tract (CST) after stroke; however, the psychometric properties of DTI‐based measures of white matter integrity are unknown. The purpose of this study was to examine test–retest reliability as determined by intraclass correlation coefficients (ICC) and calculate minimal detectable change (MDC) of DTI‐based measures of CST integrity using three different approaches: a Cerebral Peduncle approach, a Probabilistic Tract approach, and a Tract Template approach. Eighteen participants with chronic stroke underwent DTI on the same magnetic resonance imaging scanner 4 days apart. For the Cerebral Peduncle approach, a researcher hand drew masks at the cerebral peduncle. For the Probabilistic Tract approach, tractography was seeded in motor areas of the cortex to the cerebral peduncle. For the Tract Template approach, a standard CST template was transformed into native space. For all approaches, the researcher performing analyses was blind to participant number and day of data collection. All three approaches had good to excellent test–retest reliability for fractional anisotropy (FA; ICCs \u3e0.786). Mean diffusivity, axial diffusivity, and radial diffusivity were less reliable than FA. The ICC values were highest and MDC values were the smallest for the most automated approach (Tract Template), followed by the combined manual/automated approach (Probabilistic Tract) then the manual approach (Cerebral Peduncle). The results of this study may have implications for how DTI‐based measures of CST integrity are used to define impairment, predict outcomes, and interpret change after stroke

The role of the oviduct environment in embryo survival

Context: Declining fertility is an issue in multiple mammalian species. As the site of fertilisation and early embryo development, the oviduct plays a critical role in embryo survival, yet there is a paucity of information on how the oviduct regulates this process.Aims: We hypothesised that differences in steroid hormone signalling and/or immune function would be observed in a model of poor embryo survival, the peripubertal ewe.Methods: We examined expression of steroid hormones in systemic circulation, oviductal expression of oestrogen receptor α and genes important in steroid hormone signalling, and immune function in pregnant and cyclic peripubertal and adult ewes on day 3 after oestrus.Key results: Concentrations of progesterone, but not oestradiol, were decreased in the peripubertal ewe compared to the adult ewe. Oestrogen receptor α protein expression was increased in the peripubertal ewe, but pathway analysis of gene expression revealed downregulation of the oestrogen signalling pathway compared to the adult ewe. Differential expression of several genes involved in immune function between the peripubertal and adult ewe was consistent with an unfavourable oviductal environment in the peripubertal ewe lamb. Oestradiol concentration was positively correlated with the expression of multiple genes involved in the regulation of immune function.Conclusions: Differences in the immune environment of the oviduct, potentially linked to differential modulation by steroid hormones, may partially underly the poor fertilisation and early embryo survival observed in the peripubertal ewe.Implications: A unfavourable oviductal environment may play an important role in limiting reproductive success.</p

A 70,000 year multiproxy record of climatic and environmental change from Rano Aroi peatland (Easter Island)

The Rano Aroi mire on Easter Island (also known as Rapa Nui; 27°09′S, 109°27′W, 430 m above sea level) provides a unique non-marine record in the central South Pacific Ocean for reconstructing Late Pleistocene environmental changes. The results of amultiproxy study on twocores fromthe center and margin of the Rano Aroi mire,including peat stratigraphy, facies analysis, elemental and isotope geochemistry on bulk organic matter, X-ray fluorescence (XRF) core scanning and macrofossil analysis, were used to infer past water levels and vegetation changes. The chronology was based on 18 14C AMS dates for the upper 8.7 m. The extrapolated age for the base of the sequence is 70 kyr, which implies that this record is the oldest paleolimnological record on Easter Island.The recovered Rano Aroi sequence consists of a radicel peat formed primarily from the remains of sedges,grasses and Polygonaceae that have accumulated since Marine Isotopic Stage (MIS) 4 (70 kyr BP) to the present. From 60 to 40 kyr BP (MIS 3), high precipitation/runoff events were recorded as organic mud facies with lighter δ13C, low C/N values and high Ti content, indicating higher detritic input to the mire. A gradual shift in δ13C bulk organic matter from −14% to −26%, recorded between 50 and 45 cal kyr BP, suggests a progressive change in local peat-forming vegetation from C4 to C3 plant types. Post-depositional Ca and Fe enrichment during sub-aerial peat exposure and very low sedimentation rates indicate lower water tables during Late MIS 3 (39-31 cal kyr BP). During MIS 2 (27.8-19 cal kyr BP), peat production rates were very low, most likely due to cold temperatures, as reconstructed from other Easter Island records during the Last Glacial Maximum (LGM).Geochemical and macrofossil evidence shows that peat accumulation reactivates at approximately 17.5 cal kyr BP, reaching the highest accumulation rates at 14 cal kyr BP. Peat accretion decreased from 5.0 to 2.5 cal kyr BP, coinciding with a regional Holocene aridity phase. The main hydrological and environmental changes in Rano Aroi reflect variations in the South Pacific Convergence Zone (SPCZ), Southern Westerlies (SW) storm track, and South Pacific Anticyclone (SPA) locations

Correction: Decoupling of the PI3K Pathway via Mutation Necessitates Combinatorial Treatment in HER2+ Breast Cancer.

[This corrects the article DOI: 10.1371/journal.pone.0133219.]

MYC regulates ductal-neuroendocrine lineage plasticity in pancreatic ductal adenocarcinoma associated with poor outcome and chemoresistance

Neuroendocrine differentiation of epithelial tumor cells can contribute to cancer cell resistance and survival. Here, the authors show that dysregulated c-Myc promotes neuroendocrine differentiation in pancreatic ductal adenocarcinoma, leading to poor survival and chemoresistance

Decoupling of the PI3K Pathway via Mutation Necessitates Combinatorial Treatment in HER2+ Breast Cancer

<div><p>We report here on experimental and theoretical efforts to determine how best to combine drugs that inhibit HER2 and AKT in HER2⁺ breast cancers. We accomplished this by measuring cellular and molecular responses to lapatinib and the AKT inhibitors (AKT_i) GSK690693 and GSK2141795 in a panel of 22 HER2⁺ breast cancer cell lines carrying wild type or mutant PIK3CA. We observed that combinations of lapatinib plus AKT_i were synergistic in HER2⁺/PIK3CA^mut cell lines but not in HER2⁺/PIK3CA^wtcell lines. We measured changes in phospho-protein levels in 15 cell lines after treatment with lapatinib, AKT_i or lapatinib + AKT_i to shed light on the underlying signaling dynamics. This revealed that p-S6RP levels were less well attenuated by lapatinib in HER2⁺/PIK3CA^mutcells compared to HER2⁺/PIK3CA^wt cells and that lapatinib + AKT_i reduced p-S6RP levels to those achieved in HER2⁺/PIK3CA^wt cells with lapatinib alone. We also found that that compensatory up-regulation of p-HER3 and p-HER2 is blunted in PIK3CA^mut cells following lapatinib + AKT_itreatment. Responses of HER2⁺ SKBR3 cells transfected with lentiviruses carrying control or PIK3CA^mut sequences were similar to those observed in HER2⁺/PIK3CA^mut cell lines but not in HER2⁺/PIK3CA^wtcell lines. We used a nonlinear ordinary differential equation model to support the idea that PIK3CA mutations act as downstream activators of AKT that blunt lapatinib inhibition of downstream AKT signaling and that the effects of PIK3CA mutations can be countered by combining lapatinib with an AKT_i. This combination does not confer substantial benefit beyond lapatinib in HER2⁺/PIK3CA^wt cells.</p></div