Applying dynamical systems techniques to real ocean drifters

This paper presents the first comprehensive comparison of several different dynamical-systems-based measures of stirring and Lagrangian coherence, computed from real ocean drifters. Seven commonly used methods (finite-time Lyapunov exponent (FTLE), trajectory path length, trajectory correlation dimension, trajectory encounter volume, Lagrangian-averaged vorticity deviation, dilation, and spectral clustering) were applied to 144 surface drifters in the Gulf of Mexico in order to map out the dominant Lagrangian coherent structures. Among the detected structures were regions of hyperbolic nature resembling stable manifolds from classical examples, divergent and convergent zones, and groups of drifters that moved more coherently and stayed closer together than the rest of the drifters. Many methods highlighted the same structures, but there were differences too. Overall, five out of seven methods provided useful information about the geometry of transport within the domain spanned by the drifters, whereas the path length and correlation dimension methods were less useful than others.</p

The Mediating Role of Commitment and Relationship Satisfaction on Socioeconomic-Status and Stability

Abstract Predicting relationship stability has been studied in a multitude of ways; however, few articles examined the extent to which socioeconomic status, relationship satisfaction, and commitment associate with relationship stability guided by the investment model. Thus, using secondary data (N=331), Andrew Hayes’s PROCESS was used to assess whether relationship satisfaction and commitment mediated the relationship between socioeconomic status and stability while controlling for relevant relational and demographic characteristics. Results suggest that socioeconomic status was negatively related to commitment but not relationship satisfaction. Relationship satisfaction and commitment were both positively related to stability, but only commitment mediated the relationship between socioeconomic status and stability. Implications are discussed. Keywords: Stability, Mediation, Commitment, Socioeconomic Statues, Relationship Satisfactio

Cumulative Burden of Morbidity Among Testicular Cancer Survivors After Standard Cisplatin-Based Chemotherapy: A Multi-Institutional Study

Purpose In this multicenter study, we evaluated the cumulative burden of morbidity (CBM) among > 1,200 testicular cancer survivors and applied factor analysis to determine the co-occurrence of adverse health outcomes (AHOs). Patients and Methods Participants were ≤ 55 years of age at diagnosis, finished first-line chemotherapy ≥ 1 year previously, completed a comprehensive questionnaire, and underwent physical examination. Treatment data were abstracted from medical records. A CBM score encompassed the number and severity of AHOs, with ordinal logistic regression used to assess associations with exposures. Nonlinear factor analysis and the nonparametric dimensionality evaluation to enumerate contributing traits procedure determined which AHOs co-occurred. Results Among 1,214 participants, approximately 20% had a high (15%) or very high/severe (4.1%) CBM score, whereas approximately 80% scored medium (30%) or low/very low (47%). Increased risks of higher scores were associated with four cycles of either ifosfamide, etoposide, and cisplatin (odds ratio [OR], 1.96; 95% CI, 1.04 to 3.71) or bleomycin, etoposide, and cisplatin (OR, 1.44; 95% CI, 1.04 to 1.98), older attained age (OR, 1.18; 95% CI, 1.10 to 1.26), current disability leave (OR, 3.53; 95% CI, 1.57 to 7.95), less than a college education (OR, 1.44; 95% CI, 1.11 to 1.87), and current or former smoking (OR, 1.28; 95% CI, 1.02 to 1.63). CBM score did not differ after either chemotherapy regimen ( P = .36). Asian race (OR, 0.41; 95% CI, 0.23 to 0.72) and vigorous exercise (OR, 0.68; 95% CI, 0.52 to 0.89) were protective. Variable clustering analyses identified six significant AHO clusters (χ2 P < .001): hearing loss/damage, tinnitus (OR, 16.3); hyperlipidemia, hypertension, diabetes (OR, 9.8); neuropathy, pain, Raynaud phenomenon (OR, 5.5); cardiovascular and related conditions (OR, 5.0); thyroid disease, erectile dysfunction (OR, 4.2); and depression/anxiety, hypogonadism (OR, 2.8). Conclusion Factors associated with higher CBM may identify testicular cancer survivors in need of closer monitoring. If confirmed, identified AHO clusters could guide the development of survivorship care strategies

Multicolor Monitoring of Dysregulated Protein Kinases in Chronic Myelogenous Leukemia

The Bcr-Abl and Lyn protein tyrosine kinases have been separately linked to the emergence of imatinib resistance in patients with chronic myelogenous leukemia. We have developed fluorescent sensors for these kinases that are enzymatically and photophysically distinct, allowing us to simultaneously, yet separately, visualize the tyrosine kinase activities of both Abl and Lyn. Multicolor monitoring revealed that an imatinib resistant cell line (MYL-R) displays a remarkable 13-fold enhancement in Lyn kinase activity relative to its imatinib sensitive counterpart (MYL). By contrast, both cell lines display nearly identical Abl activities. The upregulation of Lyn kinase phosphotransferase activity in MYL-R cells is linked to an overexpression of the Lyn B isoform. Furthermore, MYL-R cells possess a 4-fold higher level of activated Lyn and 5-fold lower level of autoinhibited Lyn than MYL cells. Furthermore, studies with an activating SH2 ligand revealed that Lyn from imatinib-resistant MYL-R cells is primed and active, whereas Lyn from imatinib-sensitive cells is dependent upon phosphorylated SH2 ligands for activity

Latent Class Analysis of Victimization Patterns and Associated Protective Factors among LGBTQ Youth

Youth victimization in schools remains a fervent public health issue, despite increased awareness of this issue, and this is especially true for marginalized populations like lesbian, gay, bisexual, transgender, and queer (LGBTQ) youth. Youth violence has been studied widely, but less research has sought to understand factors protective of violence victimization, particularly protective factors shared across multiple forms of violence. In the current study, we utilized latent class analysis to test patterns of three types of victimization: peer victimization (PV), homophobic name-calling victimization (HNCV), and sexual harassment victimization (SHV). In addition, we tested protective factors associated with experiencing these types of violence. Our sample included 4778 9–11th graders in the United States, of which about 15% identified as LGBTQ. Three unique classes of victimization emerged, suggesting that concurrent forms of violence occur among some groups of adolescents. LGBTQ youth were more likely to be members of classes which demonstrated higher levels of victimization. Consistent with previous literature, medical access, counseling access, family support, peer support, and spirituality emerged as significant protective factors associated with a lower risk of victimization. We discuss the implications of our findings with specific attention to protecting the wellbeing of SGM youth

Measuring the impact of maternal critical care admission on short- and longer-term maternal and birth outcomes

PurposeFactors increasing the risk of maternal critical illness are rising in prevalence in maternity populations. Studies of general critical care populations highlight that severe illness is associated with longer-term physical and psychological morbidity. We aimed to compare short- and longer-term outcomes between women who required critical care admission during pregnancy/puerperium and those who did not. MethodsA cohort study including all women delivering in Scottish hospitals between 01/01/2005-31/12/2018, using national healthcare databases. The primary exposure was Intensive Care Unit (ICU) admission, whilst secondary exposures included High Dependency Unit admission. Outcomes included hospital readmission (1-year post-hospital discharge, 1-year mortality, psychiatric hospital admission, stillbirth and neonatal critical care admission). Multivariable Cox and logistic regression were used to report hazard ratios (HR) and odds ratios (OR) of association between ICU admission and outcomes. ResultsOf 762,918 deliveries, 1,449 (0.18%) women were admitted to ICU, most commonly due to post-partum haemorrhage (225, 15.5%) followed by eclampsia/pre-eclampsia (133, 9.2%). Over-half (53.8%) required mechanical ventilation. One-year hospital readmission was more frequent in women admitted to ICU compared with non-ICU populations (24.5% (n=299) vs 8.9% (n=68,029)). This association persisted after confounder adjustment (HR=1.93, 95%CI 1.33, 2.81, p&lt;0.001). Furthermore, maternal ICU admission was associated with increased 1-year mortality (HR=40.06, 95%CI 24.04,66.76, p&lt;0.001, stillbirth (OR=12.31, 95%CI 7.95,19.08,p&lt;0.001) and neonatal critical care admission (OR=6.99, 95%CI 5.64 ,8.67, p&lt;0.001) after confounder adjustment. ConclusionCritical care admission increases the risk of adverse short-term and long-term maternal, pregnancy and neonatal outcomes. Optimising long-term post-partum care may benefit maternal critical illness survivors.<br/

Rapid evolution of aerosol particles and their optical properties downwind of wildfires in the western US

During the first phase of the Biomass Burn Operational Project (BBOP) field campaign, conducted in the Pacific Northwest, the DOE G-1 aircraft was used to follow the time evolution of wildfire smoke from near the point of emission to locations 2-3.5 h downwind. In nine flights we made repeated transects of wildfire plumes at varying downwind distances and could thereby follow the plume\u27s time evolution. On average there was little change in dilution-normalized aerosol mass concentration as a function of downwind distance. This consistency hides a dynamic system in which primary aerosol particles are evaporating and secondary ones condensing. Organic aerosol is oxidized as a result. On all transects more than 90 % of aerosol is organic. In freshly emitted smoke aerosol, NH+4 is approximately equivalent to NO3. After 2 h of daytime aging, NH+4 increased and is approximately equivalent to the sum of Cl, SO24, and NO3. Particle size increased with downwind distance, causing particles to be more efficient scatters. Averaged over nine flights, mass scattering efficiency (MSE) increased in ∼ 2 h by 56 % and doubled in one flight. Mechanisms for redistributing mass from small to large particles are discussed. Coagulation is effective at moving aerosol from the Aitken to accumulation modes but yields only a minor increase in MSE. As absorption remained nearly constant with age, the time evolution of single scatter albedo was controlled by age-dependent scattering. Near-fire aerosol had a single scatter albedo (SSA) of 0.8-0.9. After 1 to 2 h of aging SSAs were typically 0.9 and greater. Assuming global-average surface and atmospheric conditions, the observed age dependence in SSA would change the direct radiative effect of a wildfire plume from near zero near the fire to a cooling effect downwind

Phosphorylation of Cytochrome c Threonine 28 Regulates Electron Transport Chain Activity in Kidney: Implications for AMP Kinase

Mammalian cytochrome c (Cytc) plays a key role in cellular life and death decisions, functioning as an electron carrier in the electron transport chain and as a trigger of apoptosis when released from the mitochondria. However, its regulation is not well understood. We show that the major fraction of Cytc iso- lated from kidneys is phosphorylated on Thr28, leading to a par- tial inhibition of respiration in the reaction with cytochrome c oxidase. To further study the effect of Cytc phosphorylation in vitro, we generated T28E phosphomimetic Cytc, revealing supe- rior behavior regarding protein stability and its ability to degrade reactive oxygen species compared with wild-type un- phosphorylated Cytc. Introduction of T28E phosphomimetic Cytc into Cytc knock-out cells shows that intact cell respiration, mitochondrial membrane potential (����m), and ROS levels are reduced compared with wild type. As we show by high resolu- tion crystallography of wild-type and T28E Cytc in combination with molecular dynamics simulations, Thr28 is located at a cen- tral position near the heme crevice, the most flexible epitope of the protein apart from the N and C termini. Finally, in silico prediction and our experimental data suggest that AMP kinase, which phosphorylates Cytc on Thr28 in vitro and colocalizes with Cytc to the mitochondrial intermembrane space in the kid- ney, is the most likely candidate to phosphorylate Thr28 in vivo. We conclude that Cytc phosphorylation is mediated in a tissue- specific manner and leads to regulation of electron transport chain flux via “controlled respiration,” preventing ����m hyperpolarization, a known cause of ROS and trigger of apoptosis

PPM1D Mutations Drive Clonal Hematopoiesis in Response to Cytotoxic Chemotherapy.

Clonal hematopoiesis (CH), in which stem cell clones dominate blood production, becomes increasingly common with age and can presage malignancy development. The conditions that promote ascendancy of particular clones are unclear. We found that mutations in PPM1D (protein phosphatase Mn2+/Mg2+-dependent 1D), a DNA damage response regulator that is frequently mutated in CH, were present in one-fifth of patients with therapy-related acute myeloid leukemia or myelodysplastic syndrome and strongly correlated with cisplatin exposure. Cell lines with hyperactive PPM1D mutations expand to outcompete normal cells after exposure to cytotoxic DNA damaging agents including cisplatin, and this effect was predominantly mediated by increased resistance to apoptosis. Moreover, heterozygous mutant Ppm1d hematopoietic cells outcompeted their wild-type counterparts in vivo after exposure to cisplatin and doxorubicin, but not during recovery from bone marrow transplantation. These findings establish the clinical relevance of PPM1D mutations in CH and the importance of studying mutation-treatment interactions. VIDEO ABSTRACT.This work was supported by the Center Prevention and Research Institute of Texas (CPRIT) (RP160451 and R120501) and the NIH (DK092883, DK116428, S10RR024574, AI036211, P30 CA125123, and P30 CA016672). The Welch Foundation (G-0040), MD Anderson’s MoonShot Program, the Baylor Research Advocates for Student Scientists, and the BCM MSTP program also provided support. K.T. is supported by a Khalifa Physician Scientist Award, the Physician Scientist Program at MD Anderson, and a Leukemia SPORE Career Enhancement Award. G.V. is funded by a Cancer Research UK Senior Cancer Research Fellowship (C22324/A23015), the Kay Kendall Leukaemia Fund, Bloodwise, and core funding from the Sanger Institute (WT098051). We also thank the Samuel Waxman Cancer Research Foundation