The Learning and Working During the Transition to Adulthood Rehabilitation Research and Training Center

Research and dissemination activities are singularly focused on developing knowledge for and about developmentally appropriate services that help transition Age Youth and Young Adults (TAYYA) with Serious Mental Health Conditions (SMHC) successfully complete their schooling and training and launch their adult working careers

Circulating cell free DNA during definitive chemo-radiotherapy in non-small cell lung cancer patients - initial observations.

BACKGROUND: The overall aim was to investigate the change over time in circulating cell free DNA (cfDNA) in patients with locally advanced non-small cell lung cancer (NSCLC) undergoing concurrent chemo-radiotherapy. Furthermore, to assess the possibility of detecting circulating cell free tumor DNA (ctDNA) using shallow whole genome sequencing (sWGS) and size selection. METHODS: Ten patients were included in a two-phase study. The first four patients had blood samples taken prior to a radiation therapy (RT) dose fraction and at 30 minutes, 1 hour and 2 hours after RT to estimate the short-term dynamics of cfDNA concentration after irradiation. The remaining six patients had one blood sample taken on six treatment days 30 minutes post treatment to measure cfDNA levels. Presence of ctDNA as indicated by chromosomal aberrations was investigated using sWGS. The sensitivity of this method was further enhanced using in silico size selection. RESULTS: cfDNA concentration from baseline to 120 min after therapy was stable within 95% tolerance limits of +/- 2 ng/ml cfDNA. Changes in cfDNA were observed during therapy with an apparent qualitative difference between adenocarcinoma (average increase of 0.69 ng/ml) and squamous cell carcinoma (average increase of 4.0 ng/ml). Tumor shrinkage on daily cone beam computer tomography scans during radiotherapy did not correlate with changes in concentration of cfDNA. CONCLUSION: Concentrations of cfDNA remain stable during the first 2 hours after an RT fraction. However, based on the sWGS profiles, ctDNA represented only a minor fraction of cfDNA in this group of patients. The detection sensitivity of genomic alterations in ctDNA strongly increases by applying size selection

Phase Field Model for Three-Dimensional Dendritic Growth with Fluid Flow

We study the effect of fluid flow on three-dimensional (3D) dendrite growth using a phase-field model on an adaptive finite element grid. In order to simulate 3D fluid flow, we use an averaging method for the flow problem coupled to the phase-field method and the Semi-Implicit Approximated Projection Method (SIAPM). We describe a parallel implementation for the algorithm, using Charm++ FEM framework, and demonstrate its efficiency. We introduce an improved method for extracting dendrite tip position and tip radius, facilitating accurate comparison to theory. We benchmark our results for two-dimensional (2D) dendrite growth with solvability theory and previous results, finding them to be in good agreement. The physics of dendritic growth with fluid flow in three dimensions is very different from that in two dimensions, and we discuss the origin of this behavior

Theory of Chiral Modulations and Fluctuations in Smectic-A Liquid Crystals Under an Electric Field

Chiral liquid crystals often exhibit periodic modulations in the molecular director; in particular, thin films of the smectic-C* phase show a chiral striped texture. Here, we investigate whether similar chiral modulations can occur in the induced molecular tilt of the smectic-A phase under an applied electric field. Using both continuum elastic theory and lattice simulations, we find that the state of uniform induced tilt can become unstable when the system approaches the smectic-A--smectic-C* transition, or when a high electric field is applied. Beyond that instability point, the system develops chiral stripes in the tilt, which induce corresponding ripples in the smectic layers. The modulation persists up to an upper critical electric field and then disappears. Furthermore, even in the uniform state, the system shows chiral fluctuations, including both incipient chiral stripes and localized chiral vortices. We compare these predictions with observed chiral modulations and fluctuations in smectic-A liquid crystals.Comment: 11 pages, including 9 postscript figures, uses REVTeX 3.0 and epsf.st

The Pine River Statement: Human Health Consequences of DDT Use

Objectives: Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction: We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis: Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions: Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDT.Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDThttp://dx.doi.org/10.1289/ehp.1174

Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples

Background: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting. Methodology: We developed and implemented an optimized mutation profiling platform (“OncoMap”) to interrogate ∼400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact. Conclusions: Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of “actionable” cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents

The Toronto Concussion Study: a prospective investigation of characteristics in a cohort of adults from the general population seeking care following acute concussion, 2016–2020

PurposeThere is limited research regarding the characteristics of those from the general population who seek care following acute concussion.MethodsTo address this gap, a large cohort of 473 adults diagnosed with an acute concussion (female participants = 287; male participants = 186) was followed using objective measures prospectively over 16 weeks beginning at a mean of 5.1 days post-injury.ResultsFalls were the most common mechanism of injury (MOI) (n = 137, 29.0%), followed by sports-related recreation (n = 119, 25.2%). Male participants were more likely to be injured playing recreational sports or in a violence-related incident; female participants were more likely to be injured by falling. Post-traumatic amnesia (PTA) was reported by 80 participants (16.9 %), and loss of consciousness (LOC) was reported by 110 (23.3%). In total, 54 participants (11.4%) reported both PTA and LOC. Male participants had significantly higher rates of PTA and LOC after their injury compared to their female counterparts. Higher initial symptom burden was associated with a longer duration of recovery for both male and female participants. Female participants had more symptoms and higher severity of symptoms at presentation compared to male participants. Female participants were identified to have a longer recovery duration, with a mean survival time of 6.50 weeks compared to 5.45 weeks in male participants (p < 0.0001). A relatively high proportion of female and male participants in this study reported premorbid diagnoses of depression and anxiety compared to general population characteristics.ConclusionAlthough premorbid diagnoses of depression and/or anxiety were associated with higher symptom burden at the initial visit, the duration of symptoms was not directly associated with a pre-injury history of psychological/psychiatric disturbance. This cohort of adults, from the general population, seeking care for their acute concussion attained clinical and functional recovery over a period of 4–12 weeks

Links Between Communication and Relationship Satisfaction Among Patients With Cancer and Their Spouses: Results of a Fourteen-Day Smartphone-Based Ecological Momentary Assessment Study

Cancer treatment poses significant challenges not just for those diagnosed with the disease but also for their intimate partners. Evidence suggests that couples' communication plays a major role in the adjustment of both individuals and in the quality of their relationship. Most descriptive studies linking communication to adjustment have relied on traditional questionnaire methodologies and cross-sectional designs, limiting external validity and discernment of temporal patterns. Using the systemic-transactional model of dyadic coping as a framework, we examined intra- and inter-personal associations between communication (both enacted and perceived) and relationship satisfaction (RS) among patients with stage II–IV breast or colorectal cancer and their spouses (N = 107 couples). Participants (mean age = 51, 64.5% female patients, and 37.4% female spouses) independently completed twice-daily ecological momentary assessments (EMA) via smartphone for 14 consecutive days. Items assessed RS and communication (expression of feelings, holding back from expression, support and criticism of partner, and parallel ratings of partner behavior). Linear mixed models employing an Actor Partner Interdependence Model were used to examine concurrent, time-lagged, and cross-lagged associations between communication and RS. Expressing one's feelings was unassociated with RS. Holding back from doing so, in contrast, was associated with lower RS for both patients and spouses in concurrent models. These effects were both intrapersonal and interpersonal, meaning that when individuals held back from expressing their feelings, they reported lower RS and so too did their partner. Giving and receiving support were associated with one's own higher RS for both patients and spouses in concurrent models, and for patients in lagged models. Conversely, criticizing one's partner and feeling criticized were maladaptive, associated with lower RS (own and in some cases, partner's). Cross-lagged analyses (evening RS to next-day afternoon communication) yielded virtually no effects, suggesting that communication may have a stronger influence on short-term RS than the reverse. Findings underscore the importance of responsive communication, more so than expression per se, in explaining both concurrent and later relationship adjustment. In addition, a focus on holding back from expressing feelings may enhance the understanding of RS for couples coping with cancer

Couple Communication in Cancer: Protocol for a Multi-Method Examination

Cancer and its treatment pose challenges that affect not only patients but also their significant others, including intimate partners. Accumulating evidence suggests that couples’ ability to communicate effectively plays a major role in the psychological adjustment of both individuals and the quality of their relationship. Two key conceptual models have been proposed to account for how couple communication impacts psychological and relationship adjustment: the social-cognitive processing (SCP) model and the relationship intimacy (RI) model. These models posit different mechanisms and outcomes, and thus have different implications for intervention. The purpose of this project is to test and compare the utility of these models using comprehensive and methodologically rigorous methods. Aims are: (1) to examine the overall fit of the SCP and RI models in explaining patient and partner psychological and relationship adjustment as they occur on a day-to-day basis and over the course of 1 year; (2) to examine the fit of the models for different subgroups (males vs. females, and patients vs. partners); and (3) to examine the utility of various methods of assessing communication by examining the degree to which baseline indices from different measurement strategies predict self-reported adjustment at 1-year follow up. The study employs a longitudinal, multi-method approach to examining communication processes including: standard self-report questionnaires assessing process and outcome variables collected quarterly over the course of 1 year; smartphone-based ecological momentary assessments to sample participant reports in real time; and laboratory-based couple conversations from which we derive observational measures of communicative behavior and affective expression, as well as vocal indices of emotional arousal. Participants are patients with stage II-IV breast, colon, rectal, or lung cancer and their spouses/partners, recruited from two NCI-designated comprehensive cancer centers. Results will be published in scientific journals, presented at scientific conferences, and conveyed to a larger audience through infographics and social media outlets. Findings will inform theory, measurement, and the design and implementation of efficacious interventions aimed at optimizing both patient and partner well-being