To evaluate the diagnostic performance of radiomic signatures extracted from contrast-enhanced magnetic resonance imaging (CE-MRI) for the assessment of breast cancer receptor status and molecular ...subtypes.
One hundred and forty-three patients with biopsy-proven breast cancer who underwent CE-MRI at 3 T were included in this IRB-approved HIPAA-compliant retrospective study. The training dataset comprised 91 patients (luminal A, n = 49; luminal B, n = 8; HER2-enriched, n = 11; triple negative, n = 23), while the validation dataset comprised 52 patients from a second institution (luminal A, n = 17; luminal B, n = 17; triple negative, n = 18). Radiomic analysis of manually segmented tumors included calculation of features derived from the first-order histogram (HIS), co-occurrence matrix (COM), run-length matrix (RLM), absolute gradient (GRA), autoregressive model (ARM), discrete Haar wavelet transform (WAV), and lesion geometry (GEO). Fisher, probability of error and average correlation (POE + ACC), and mutual information coefficients were used for feature selection. Linear discriminant analysis followed by k-nearest neighbor classification (with leave-one-out cross-validation) was used for pairwise radiomic-based separation of receptor status and molecular subtypes. Histopathology served as the standard of reference.
In the training dataset, radiomic signatures yielded the following accuracies > 80%: luminal B vs. luminal A, 84.2% (mainly based on COM features); luminal B vs. triple negative, 83.9% (mainly based on GEO features); luminal B vs. all others, 89% (mainly based on COM features); and HER2-enriched vs. all others, 81.3% (mainly based on COM features). Radiomic signatures were successfully validated in the separate validation dataset for luminal A vs. luminal B (79.4%) and luminal B vs. triple negative (77.1%).
In this preliminary study, radiomic signatures with CE-MRI enable the assessment of breast cancer receptor status and molecular subtypes with high diagnostic accuracy. These results need to be confirmed in future larger studies.
The pattern‐reversal visual evoked potential (prVEP) is an established routine clinical test. Its objectivity is particularly valuable for assessing visual pathway function in children. International ...standards specify at a minimum that an active electrode is placed on the occiput at Oz, but we find an additional inferior electrode at the inion (Iz) provides larger and more sensitive prVEPs in young persons. This study assesses the significance and age‐dependence of these observations. PrVEPs were recorded from 1487 patients considered ophthalmologically normal aged <20 years old, to a range of check widths including International Society for Clinical Electrophysiology of Vision (ISCEV) standard large (50′) and small (12.5′) check widths. P100 peak‐time and amplitude from both electrode sites were analysed. A subset of 256 children were studied longitudinally by fitting logistic regression models including a random effect on subjects. PrVEPs were largest over the Iz electrode for the majority of infants and children. This transitioned with age to become equal or smaller at Oz as a function of check width. For ISCEV standard large and small check widths, transition periods were ∼8 and ∼12 years of age, respectively. We estimated abnormal result classifications of 3.7% with use of an Oz electrode alone, which decreases to 0.0–0.5% when adding or using an Iz electrode. The inferior dominance of prVEP topography in children may be explained by age‐related anatomical changes altering the cortical dipole, combined with physiological maturation of the neural generators of the prVEP. We recommend the Iz electrode is used routinely in recording of prVEPs in children.
Key points
Pattern visual evoked potentials (PVEPs) are an established clinical test which provide objective assessment of visual pathway function. These are particularly valuable in providing objective information of vision in children.
International standards specify the active recording electrode should be placed at the mid‐occiput (Oz), but we find that pattern‐reversal visual evoked potential amplitudes are larger for a lower placed electrode (Iz) in young persons.
This was assessed in 1487 patients who had simultaneous PVEP recording at both electrode positions, and it was found that the majority of PVEPs in children were larger over the Iz electrode.
The developmental differences in PVEP distribution transitioned to be equal between Iz and Oz with increasing age as a function of check width, at ∼8 and ∼12 years old for large and small check widths, respectively.
These differences will improve diagnostic accuracy of paediatric PVEPs. We hypothesise these changes reflect developmental anatomical and neurophysiological changes altering the PVEP dipole.
figure legend Schematic representation of prVEP response measurement. Responses were recorded from mid‐occipital (Oz) and inion (Iz) electrodes simultaneously, referred to a mid‐frontal electrode (Fz) and ground centrally (Cz). Peak‐time was taken from stimulus onset (0 ms) to peak of the P100 component (red dashed line). Amplitude was taken from the N75 trough to P100 peak (red vertical line).
► Review to study anthelmitics. ► Physicochemical properties, fate in the environment and ecotoxicity. ► Environmental levels of anthelmintics. ► Overview of analytical methodologies and sample ...preparation.
There has been a great effort made in recent years to study the fate, the occurrence and the ecotoxicology of emerging pollutants in the environment, with a particular emphasis on pharmaceuticals. Anthelmintics comprise a large sector of the animal pharmaceutical industry.
This article examines analytical methodologies for the analysis of anthelmintics and their transformation products (TPs) in the environment. It also gives a critical overview of the current knowledge on the fate and the ecotoxicology of anthelmintics and their TPs, if known.
A subset of patients with stable asthma has prominent neutrophilic and reduced eosinophilic inflammation, which is associated with attenuated airways hyper-responsiveness (AHR). Haemophilus ...influenzae has been isolated from the airways of neutrophilic asthmatics; however, the nature of the association between infection and the development of neutrophilic asthma is not understood. Our aim was to investigate the effects of H. influenzae respiratory infection on the development of hallmark features of asthma in a mouse model of allergic airways disease (AAD). BALB/c mice were intraperitoneally sensitized to ovalbumin (OVA) and intranasally challenged with OVA 12-15 days later to induce AAD. Mice were infected with non-typeable H. influenzae during or 10 days after sensitization, and the effects of infection on the development of key features of AAD were assessed on day 16. T-helper 17 cells were enumerated by fluorescent-activated cell sorting and depleted with anti-IL-17 neutralizing antibody. We show that infection in AAD significantly reduced eosinophilic inflammation, OVA-induced IL-5, IL-13 and IFN-γ responses and AHR; however, infection increased airway neutrophil influx in response to OVA challenge. Augmented neutrophilic inflammation correlated with increased IL-17 responses and IL-17 expressing macrophages and neutrophils (early, innate) and T lymphocytes (late, adaptive) in the lung. Significantly, depletion of IL-17 completely abrogated infection-induced neutrophilic inflammation during AAD. In conclusion, H. influenzae infection synergizes with AAD to induce Th17 immune responses that drive the development of neutrophilic and suppress eosinophilic inflammation during AAD. This results in a phenotype that is similar to neutrophilic asthma. Infection-induced neutrophilic inflammation in AAD is mediated by IL-17 responses.
This article presents a case study of parents' involvement with their third-grade children. Using interviews and classroom observations, the research revealed how some black parents, deeply concerned ...about the historical legacy of discrimination against blacks in schooling, approach the school with open criticisms. Since educators seek a positive and deferential role for parents in schooling, race appears to play an independent role in parents' ability to comply with educators' requests (although social class also mediates the ways in which black parents express their concerns). The results highlight the difference between possession and activation of capital and the value accorded displays of capital in particular settings. Taken together, the findings suggest the importance of focusing on moments of inclusion and exclusion in examining how individuals activate social and cultural capital. (DIPF/orig.)
In the Netherlands, maternity care is divided into midwife-led care (for low-risk women) and obstetrician-led care (for high-risk women). Referrals from midwife-led to obstetrician-led care have ...increased over the past decade. The majority of women are referred during their pregnancy or labour. Referrals are based on a continuous risk assessment of the health and characteristics of mother and child, yet referral for non-medical factors and characteristics remain unclear. This study investigated which maternal characteristics are associated with women's referral from midwife-led to obstetrician-led care.
A retrospective cohort study in one midwife-led care practice in the Netherlands included 1096 low-risk women during January 2015-17. The primary outcomes were referral from midwife-led to obstetrician-led care in (1) the antepartum period and (2) the intrapartum period. In total, 11 maternal characteristics were identified. Logistic regression models of referral in each period were fitted and stratified by parity.
In the antepartum period, referral among nulliparous women was associated with an older maternal age (aOR, 1.07; 95%CI, 1.05-1.09), being underweight (0.45; 0.31-0.64), overweight (2.29; 1.91-2.74), or obese (2.65; 2.06-3.42), a preconception period >1 year (1.34; 1.07-1.66), medium education level (0.76; 0.58-1.00), deprivation (1.87; 1.54-2.26), and sexual abuse (1.44; 1.14-1.82). Among multiparous women, a referral was associated with being underweight (0.40; 0.26-0.60), obese (1.61; 1.30-1.98), a preconception period >1 year (1.71; 1.27-2.28), employment (1.38; 1.19-1.61), deprivation (1.23; 1.03-1.46), highest education level (0.63; 0.51-0.80), psychological problems (1.24; 1.06-1.44), and one or multiple consultations with an obstetrician (0.68; 0.58-0.80 and 0.64; 0.54-0.76, respectively). In the intrapartum period, referral among nulliparous women was associated with an older maternal age (1.02; 1.00-1.05), being underweight (1.67; 1.15-2.42), a preconception period >1 year (0.42; 0.31-0.57), medium or high level of education (2.09; 1.49-2.91 or 1.56; 1.10-2.22, respectively), sexual abuse (0.46; 0.33-0.63), and multiple consultations with an obstetrician (1.49; 1.15-1.94). Among multiparous women, referral was associated with an older maternal age (1.02; 1.00-1.04), being overweight (0.65; 0.51-0.83), a preconception period >1 year (0.33; 0.17-0.65), non-Dutch ethnicity (1.98; 1.61-2.45), smoking (0.75; 0.57-0.97), sexual abuse (1.49; 1.09-2.02), and one or multiple consultations with an obstetrician (1.34; 1.06-1.70 and 2.09; 1.63-2.69, respectively).
This exploratory study showed that several non-medical maternal characteristics of low-risk pregnant women are associated with referral from midwife-led to obstetrician-led care, and how these differ by parity and partum period.
Background Cigarette smoke–induced chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory disorder of the lung. The development of effective therapies for COPD has been ...hampered by the lack of an animal model that mimics the human disease in a short timeframe. Objectives We sought to create an early-onset mouse model of cigarette smoke–induced COPD that develops the hallmark features of the human condition in a short time-frame. We also sought to use this model to better understand pathogenesis and the roles of macrophages and mast cells (MCs) in patients with COPD. Methods Tightly controlled amounts of cigarette smoke were delivered to the airways of mice, and the development of the pathologic features of COPD was assessed. The roles of macrophages and MC tryptase in pathogenesis were evaluated by using depletion and in vitro studies and MC protease 6–deficient mice. Results After just 8 weeks of smoke exposure, wild-type mice had chronic inflammation, mucus hypersecretion, airway remodeling, emphysema, and reduced lung function. These characteristic features of COPD were glucocorticoid resistant and did not spontaneously resolve. Systemic effects on skeletal muscle and the heart and increased susceptibility to respiratory tract infections also were observed. Macrophages and tryptase-expressing MCs were required for the development of COPD. Recombinant MC tryptase induced proinflammatory responses from cultured macrophages. Conclusion A short-term mouse model of cigarette smoke–induced COPD was developed in which the characteristic features of the disease were induced more rapidly than in existing models. The model can be used to better understand COPD pathogenesis, and we show a requirement for macrophages and tryptase-expressing MCs.
Observing Waves in Sea Ice With ICESat‐2 Horvat, C.; Blanchard‐Wrigglesworth, Ed; Petty, A.
Geophysical research letters,
28 May 2020, Volume:
47, Issue:
10
Journal Article
Peer reviewed
Open access
The coupled interaction of ocean surface waves and sea ice is important in determining the thermodynamic and dynamic properties of sea ice and its relationship to the ocean and atmosphere. Wave‐ice ...interactions create the marginal ice zone (MIZ), a region critically important for ecology, transportation, and the polar energy budget. Typically, the MIZ is defined using satellite products as those regions where sea ice concentration is between 15% and 80%. Here we present a new technique to observe ocean surface waves in sea ice, leveraging NASA's ICESat‐2 satellite laser altimeter, and produce maps of wave‐affected sea ice regions in both hemispheres. Defining a new wave‐based metric for MIZ extent, we find that compared to a concentration‐based metric, wave‐based MIZ estimates are smaller. Further, the wave‐affected MIZ makes up a larger fraction of sea ice extent in winter than in summer, opposite to the seasonal cycle of concentration‐based MIZ.
Key Points
Ocean surface waves propagating through sea ice can be observed in IceSat‐2 altimetry
Filtering for areas of wave‐ice activity, we create global maps of wave‐affected sea ice regions and the marginal ice zone
Marginal ice zone extent differs in magnitude and seasonal cycle when defined by wave activity versus sea ice concentration
Severe sepsis in immunocompromised children is associated with increased mortality. This paper describes the epidemiology landscape, clinical acuity, and outcomes for severe sepsis in pediatric ...intestinal (ITx) and multi‐visceral (MVTx) transplant recipients requiring admission to the pediatric intensive care unit (PICU). Severe sepsis episodes were retrospectively reviewed in 51 ITx and MVTx patients receiving organs between 2009 and 2015. Twenty‐nine (56.8%) patients had at least one sepsis episode (total of 63 episodes) through December 2016. Bacterial etiologies accounted for 66.7% of all episodes (n = 42), occurring a median of 122.5 days following transplant (IQR 59–211.8 days). Multidrug‐resistant organisms (MDROs) accounted for 73.8% of bacterial infections; extended spectrum beta‐lactamase producers, vancomycin‐resistant enterococcus, and highly‐resistant Pseudomonas aeruginosa were the most commonly identified. Increased mechanical ventilation and vasoactive requirements were noted in MDRO episodes (OR 3.03, 95% CI 1.09–8.46 and OR 3.07, 95% CI 1.09–8.61, respectively; p < .05) compared to non‐MDRO episodes. PICU length of stay was significantly increased for MDRO episodes (7 vs. 3 days, p = .02). Graft loss was 24.1% (n = 7) and mortality was 24.1% (n = 7) in patients who experienced severe sepsis. Further attention is needed for MDRO risk mitigation and modification of sepsis treatment guidelines to ensure MDRO coverage for this population.
In pediatric intestinal and multi‐visceral transplant recipients, MDROs account for a large majority of severe sepsis episodes related to bacterial infections and are associated with an increased need for mechanical ventilation, use of vasoactive medications, and length of intensive care unit stay.
Summary
Severe, steroid‐resistant asthma is clinically and economically important since affected individuals do not respond to mainstay corticosteroid treatments for asthma. Patients with this ...disease experience more frequent exacerbations of asthma, are more likely to be hospitalized, and have a poorer quality of life. Effective therapies are urgently required, however, their development has been hampered by a lack of understanding of the pathological processes that underpin disease. A major obstacle to understanding the processes that drive severe, steroid‐resistant asthma is that the several endotypes of the disease have been described that are characterized by different inflammatory and immunological phenotypes. This heterogeneity makes pinpointing processes that drive disease difficult in humans. Clinical studies strongly associate specific respiratory infections with severe, steroid‐resistant asthma. In this review, we discuss key findings from our studies where we describe the development of representative experimental models to improve our understanding of the links between infection and severe, steroid‐resistant forms of this disease. We also discuss their use in elucidating the mechanisms, and their potential for developing effective therapeutic strategies, for severe, steroid‐resistant asthma. Finally, we highlight how the immune mechanisms and therapeutic targets we have identified may be applicable to obesity‐or pollution‐associated asthma.
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