Piloting Signs of Safety : A Deaf-Accessible Toolkit for Trauma and Addiction

The Deaf community - a minority group of 500,000 Americans who use American Sign Language (ASL) - experiences trauma and addiction at rates double to the general population. Yet, there are no evidence-based treatments that have been evaluated to treat trauma, addiction, or other behavioral health conditions among Deaf people. Current evidence-based treatments fail to meet the needs of Deaf clients. One example is Seeking Safety, a well-validated therapy for people recovering from trauma and addiction. Seeking Safety includes a therapist guide and client handouts for 25 therapy sessions, each teaching clients a safe coping skill. When Seeking Safety was used with Deaf clients, unique barriers were revealed with regard to the client materials: they were presented in complex English instead of ASL, nor sensitive to Deaf people’s culture, social norms, and history of oppression. To address these barriers, Dr. Anderson assembled a team of Deaf and hearing researchers, clinicians, filmmakers, actors, artists, and Deaf people in recovery to develop Signs of Safety, a Deaf-accessible toolkit to be used with Seeking Safety. Signs of Safety is comprised of a therapist companion guide and population-specific client materials, including visual handouts and ASL teaching stories on digital video, which present key learning points via an “educational soap opera.” Dr. Anderson is currently leading a pilot study of Signs of Safety. Preliminary results show that participants are reporting symptom reduction from baseline to follow-up and high levels of satisfaction with the model, giving us the confidence to further pursue this line of research

Symptom Patterns of Posttraumatic Stress Disorder among Deaf Trauma Survivors

Details about Deaf people’s pattern of posttraumatic stress disorder (PTSD) symptoms remain relatively unknown due to inaccessible methods used in most epidemiological research. We conducted semi-structured American Sign Language interviews with 16 trauma-exposed Deaf individuals to explore their PTSD symptom patterns. Half met criteria for current PTSD, a rate higher than the general population. Underlying this disparity may be heightened rates of dissociation and psychogenic amnesia reported by many Deaf trauma survivors. Future research with large samples of Deaf survivors is needed to clarify this hypothesis, and to inform interventions that more accurately target Deaf people’s pattern of trauma symptoms

DNA repair deficiency biomarkers and the 70-gene ultra-high risk signature as predictors of veliparib/carboplatin response in the I-SPY 2 breast cancer trial.

Veliparib combined with carboplatin (VC) was an experimental regimen evaluated in the biomarker-rich neoadjuvant I-SPY 2 trial for breast cancer. VC showed improved efficacy in the triple negative signature. However, not all triple negative patients achieved pathologic complete response and some HR+HER2- patients responded. Pre-specified analysis of five DNA repair deficiency biomarkers (BRCA1/2 germline mutation; PARPi-7, BRCA1ness, and CIN70 expression signatures; and PARP1 protein) was performed on 116 HER2- patients (VC: 72 and concurrent controls: 44). We also evaluated the 70-gene ultra-high risk signature (MP1/2), one of the biomarkers used to define subtype in the trial. We used logistic modeling to assess biomarker performance. Successful biomarkers were combined using a simple voting scheme to refine the 'predicted sensitive' group and Bayesian modeling used to estimate the pathologic complete response rates. BRCA1/2 germline mutation status associated with VC response, but its low prevalence precluded further evaluation. PARPi-7, BRCA1ness, and MP1/2 specifically associated with response in the VC arm but not the control arm. Neither CIN70 nor PARP1 protein specifically predicted VC response. When we combined the PARPi-7 and MP1/2 classifications, the 42% of triple negative patients who were PARPi7-high and MP2 had an estimated pCR rate of 75% in the VC arm. Only 11% of HR+/HER2- patients were PARPi7-high and MP2; but these patients were also more responsive to VC with estimated pathologic complete response rates of 41%. PARPi-7, BRCA1ness and MP1/2 signatures may help refine predictions of VC response, thereby improving patient care

Disk and Envelope Structure in Class 0 Protostars: I. The Resolved Massive Disk in Serpens FIRS 1

We present the first results of a program to characterize the disk and envelope structure of typical Class 0 protostars in nearby low-mass star forming regions. We use Spitzer IRS mid-infrared spectra, high resolution CARMA 230 GHz continuum imaging, and 2-D radiative transfer models to constrain the envelope structure, as well as the size and mass of the circum-protostellar disk in Serpens FIRS 1. The primary envelope parameters (centrifugal radius, outer radius, outflow opening angle, and inclination) are well constrained by the spectral energy distribution (SED), including Spitzer IRAC and MIPS photometry, IRS spectra, and 1.1 mm Bolocam photometry. These together with the excellent uv-coverage (4.5-500 klam) of multiple antenna configurations with CARMA allow for a robust separation of the envelope and a resolved disk. The SED of Serpens FIRS 1 is best fit by an envelope with the density profile of a rotating, collapsing spheroid with an inner (centrifugal) radius of approximately 600 AU, and the millimeter data by a large resolved disk with Mdisk~1.0 Msun and Rdisk~300 AU. These results suggest that large, massive disks can be present early in the main accretion phase. Results for the larger, unbiased sample of Class~0 sources in the Perseus, Serpens, and Ophiuchus molecular clouds are needed to determine if relatively massive disks are typical in the Class 0 stage.Comment: Comments: 13 pages, 8 figures, 3 tables; accepted for publication in the Ap

A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila

Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol

Pharmacokinetic, neurochemical, stereological and neuropathological studies on the potential effects of paraquat in the substantia nigra pars compacta and striatum of male C57BL/6J mice

AbstractThe pharmacokinetics and neurotoxicity of paraquat dichloride (PQ) were assessed following once weekly administration to C57BL/6J male mice by intraperitoneal injection for 1, 2 or 3 weeks at doses of 10, 15 or 25mg/kg/week. Approximately 0.3% of the administered dose was taken up by the brain and was slowly eliminated, with a half-life of approximately 3 weeks. PQ did not alter the concentration of dopamine (DA), homovanillic acid (HVA) or 3,4-dihydroxyphenylacetic acid (DOPAC), or increase dopamine turnover in the striatum. There was inconsistent stereological evidence of a loss of DA neurons, as identified by chromogenic or fluorescent-tagged antibodies to tyrosine hydroxylase in the substantia nigra pars compacta (SNpc). There was no evidence that PQ induced neuronal degeneration in the SNpc or degenerating neuronal processes in the striatum, as indicated by the absence of uptake of silver stain or reduced immunolabeling of tyrosine-hydroxylase-positive (TH+) neurons. There was no evidence of apoptotic cell death, which was evaluated using TUNEL or caspase 3 assays. Microglia (IBA-1 immunoreactivity) and astrocytes (GFAP immunoreactivity) were not activated in PQ-treated mice 4, 8, 16, 24, 48, 96 or 168h after 1, 2 or 3 doses of PQ.In contrast, mice dosed with the positive control substance, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 10mg/kg/dose×4 doses, 2h apart), displayed significantly reduced DA and DOPAC concentrations and increased DA turnover in the striatum 7 days after dosing. The number of TH+ neurons in the SNpc was reduced, and there were increased numbers of degenerating neurons and neuronal processes in the SNpc and striatum. MPTP-mediated cell death was not attributed to apoptosis. MPTP activated microglia and astrocytes within 4h of the last dose, reaching a peak within 48h. The microglial response ended by 96h in the SNpc, but the astrocytic response continued through 168h in the striatum.These results bring into question previous published stereological studies that report loss of TH+ neurons in the SNpc of PQ-treated mice. This study also suggests that even if the reduction in TH+ neurons reported by others occurs in PQ-treated mice, this apparent phenotypic change is unaccompanied by neuronal cell death or by modification of dopamine levels in the striatum

Seasonal plankton dynamics in Kongsfjorden during two years of contrasting environmental conditions

Seasonal plankton time-series data are presented from Kongsfjorden from two years with contrasting environmental conditions. Kongsfjorden (west coast of Spitsbergen – 79°N) integrates inputs from Atlantic and Arctic waters, and glacier run-off, and is thus a prime location to study impacts on ecosystem dynamics of key environmental drivers that are relevant across the Arctic. Despite extensive research in Kongsfjorden, seasonally-resolved data are scarce. From late April/early May to early September 2019 and 2020, we conducted pelagic sampling at a mid-fjord station at mostly weekly to bi-weekly resolution investigating the environmental drivers of phyto- and zooplankton community composition and phenology. During spring 2019, Atlantic water masses with temperatures > 1 °C were found throughout the upper 250 m of the water column, and little sea ice occurred in the fjord. Spring 2020, in turn, was characterized by the presence of local water masses with sub-zero temperatures and relatively extensive sea-ice cover. The most striking contrast between the two years was the difference in phytoplankton spring bloom composition. In 2019, the spring bloom was dominated by the colonial stage of the haptophyte Phaeocystis pouchetii and diatoms played a minor role, while the spring bloom in 2020 was dominated by diatoms of the genus Thalassiosira succeeded by P. pouchetii. Selective grazing by large copepods and water mass structure seem to have been the decisive factors explaining the marked difference in diatom spring bloom biomass between the years while similar spring abundances of P. pouchetii in both years indicated that this species was less impacted by those factors. Our data suggest that differences in spring bloom composition impacted trophic transfer and carbon export. Recruitment of the dominant copepods Calanus finmarchicus and C. glacialis, Cirripedia and euphausiid larvae as well as the export of carbon to the seabed was more efficient during the diatom-dominated compared to the P. pouchetii–dominated spring bloom. In summer, the plankton composition shifted towards a flagellate-dominated community characterized by mixo- and heterotrophic taxa adapted to a lower nutrient regime and strong top-down control by copepod grazers. However, residual silicic acid after the P. pouchetii–dominated spring bloom fueled a late summer diatom bloom in 2019. Our data provide a first glimpse into the environmental drivers of plankton phenology and underline that high-resolution monitoring over many annual cycles is required to resolve the ephemeral variations of plankton populations against the backdrop of climate change.publishedVersio

Exoplanet Diversity in the Era of Space-based Direct Imaging Missions

This whitepaper discusses the diversity of exoplanets that could be detected by future observations, so that comparative exoplanetology can be performed in the upcoming era of large space-based flagship missions. The primary focus will be on characterizing Earth-like worlds around Sun-like stars. However, we will also be able to characterize companion planets in the system simultaneously. This will not only provide a contextual picture with regards to our Solar system, but also presents a unique opportunity to observe size dependent planetary atmospheres at different orbital distances. We propose a preliminary scheme based on chemical behavior of gases and condensates in a planet's atmosphere that classifies them with respect to planetary radius and incident stellar flux.Comment: A white paper submitted to the National Academy of Sciences Exoplanet Science Strateg

Human immune and gut microbial parameters associated with inter-individual variations in COVID-19 mRNA vaccine-induced immunity

COVID-19 mRNA vaccines induce protective adaptive immunity against SARS-CoV-2 in most individuals, but there is wide variation in levels of vaccine-induced antibody and T-cell responses. However, the mechanisms underlying this inter-individual variation remain unclear. Here, using a systems biology approach based on multi-omics analyses of human blood and stool samples, we identified several factors that are associated with COVID-19 vaccine-induced adaptive immune responses. BNT162b2-induced T cell response is positively associated with late monocyte responses and inversely associated with baseline mRNA expression of activation protein 1 (AP-1) transcription factors. Interestingly, the gut microbial fucose/rhamnose degradation pathway is positively correlated with mRNA expression of AP-1, as well as a gene encoding an enzyme producing prostaglandin E2 (PGE2), which promotes AP-1 expression, and inversely correlated with BNT162b2-induced T-cell responses. These results suggest that baseline AP-1 expression, which is affected by commensal microbial activity, is a negative correlate of BNT162b2-induced T-cell responses.journal articl

Guideline for the Management of Fever and Neutropenia in Pediatric Patients With Cancer and Hematopoietic Cell Transplantation Recipients: 2023 Update.

PURPOSE To update a clinical practice guideline (CPG) for the empiric management of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic cell transplantation recipients. METHODS The International Pediatric Fever and Neutropenia Guideline Panel reconvened to conduct the second update of this CPG. We updated the previous systematic review to identify new randomized controlled trials (RCTs) evaluating any strategy for the management of FN in pediatric patients. Using the Grading of Recommendations Assessment, Development and Evaluation framework, evidence quality was classified as high, moderate, low, or very low. The panel updated recommendations related to initial management, ongoing management, and empiric antifungal therapy. Changes from the 2017 CPG were articulated, and good practice statements were considered. RESULTS We identified 10 new RCTs in addition to the 69 RCTs identified in previous FN CPGs to inform the 2023 FN CPG. Changes from the 2017 CPG included two conditional recommendations regarding (1) discontinuation of empiric antibacterial therapy in clinically well and afebrile patients with low-risk FN if blood cultures remain negative at 48 hours despite no evidence of marrow recovery and (2) pre-emptive antifungal therapy for invasive fungal disease in high-risk patients not receiving antimold prophylaxis. The panel created a good practice statement to initiate FN CPG-consistent empiric antibacterial therapy as soon as possible in clinically unstable febrile patients. CONCLUSION The updated FN CPG incorporates important modifications on the basis of recently published trials. Future work should focus on addressing knowledge gaps, improving CPG implementation, and measuring the impact of CPG-consistent care