Childhood Trauma And Emotion Processing Neurocircuitry

Childhood trauma is one of the strongest risk factors for a range of common and debilitating neuropsychiatric disorders, including anxiety, depression, and posttraumatic stress disorder (PTSD). These emotion-related disorders have their roots in childhood and adolescence, underscoring a critical need to understand their biological bases in early life. In this dissertation, we evaluate how childhood trauma impacts emotion processing neurocircuitry in a sample of high-risk urban youth, ages 7-15. In four inter-related studies, we test neural function and functional connectivity of core emotion processing regions, including the amygdala, insula, and pregenual/subgenual anterior cingulate cortex (pgACC/sgACC). To examine the relevance of observed neurological changes, we evaluate behavioral performance on emotion processing neuropsychological tasks, as well as specific dimensions of subjective affective experience. Results indicate that, relative to matched comparison youth, trauma-exposed youth have (1) increased neural response to salient emotional cues in amygdala and insula, (2) reduced functional connectivity between amygdala and pgACC/sgACC, a pathway critical for emotion regulation, and (3) altered within- and between-network connectivity of the salience network, involved in detecting and orienting attention to salient emotional stimuli. These neurological changes are accompanied by behavioral alterations: trauma-exposed youth have a lower ability to ignore distracting emotional information, and to automatically regulate emotion. Additionally, observed neurobehavioral changes relate to a specific dimension of affective experience – reward sensitivity (RS), rather than negative affect. Moreover, trauma-exposed youth with the greatest neurobehavioral impairment report lower RS, suggesting reduced positive environmental engagement. These results suggest that RS may be a marker of stress susceptibility, a notion supported by emerging basic and clinical research. Based on our neurobehavioral findings, we discuss potential implications for intervention, and relay an emerging framework that dissociates neurological effects of different trauma types (i.e., threat/victimization vs. deprivation/neglect). In closing, we discuss future directions, including longitudinal research and evaluating the modulation of learned fear – a neurobehavioral mechanism that depends on emotion processing neurocircuitry, but has yet to be tested in trauma-exposed youth

Picoliter Solder Droplet Dispensing

A device based on ink-jet printing technology was used to produce and place molten solder droplets, approximately 25-125pm in diameter, onto substrates. The advantages of an ink-jet based system are direct production of metallic objects, no postcure, low cost, and the repeatability and resolution for small feature sizes. This paper describes the device, the supporting hardware, and experimental procedures. Results show that bump size can be varied by placing in quick succession, multiple droplets as well as by resizing the device and by altering the signal.Mechanical Engineerin

Personal Jurisdiction in Hatch-Waxman Cases

The Hatch-Waxman Act drastically altered the way pioneer and generic pharmaceutical manufacturers litigate patent infringement disputes, allowing generic manufacturers to submit an abbreviated new drug application (ANDA) to the FDA, which states that it intends make a chemical equivalent of a patent owner’s drug. When the ANDA is accompanied by a Paragraph IV certification, representing that the generic intends to market the drug before the patent’s expiration because it believes the patent is invalid or will not be infringed by the generic’s drug, the ANDA submission itself creates an “artificial” act of infringement. With the Supreme Court’s recent tightening of general personal jurisdiction, many pioneers seeking to litigate these “artificial” infringement claims relied on a theory of specific personal jurisdiction to bring suits against defendants in their chosen forums. Consequently, it is important that courts hearing these cases clearly understand how they must apply the prongs of the specific jurisdiction “minimum contacts” analysis. However, in the decades following the Supreme Court’s decision in Helicopteros, which introduced the so-called “nexus” test – the requirement that courts must determine whether the litigation “arises from or relates to” the defendant’s contacts with a forum – the Supreme Court has provided frustrating little guidance for interpreting this requirement, leaving it up to lower courts to decide their preferred approach. This lack of guidance is particularly problematic in Paragraph IV cases, because the litigation is “artificial,” arising almost out of thin air when the generic submits an ANDA. Thus, a defendant’s contacts with a forum in these cases are, by nature, much more tenuous than a typical defendant’s contacts in a typical infringement suit. This Comment reviews a recent case decided by the Federal Circuit, Acorda Therapeutics, Inc. v. Mylan Pharmaceuticals, Inc., in which the Federal Circuit considered the “nexus” requirement within the context of a Paragraph IV case, but failed to provide the type of clarity that Paragraph IV cases desperately need. Furthermore, this Comment argues that the public policy considerations behind the Hatch-Waxman Act support a permissive interpretation of the Helicopteros “nexus” requirement in Paragraph IV cases, and urges the Federal Circuit to adopt the “sliding scale” test favored in other circuits for these types of suits in the future

Sleep Timing and Neurocognitive Networks in Youth

Sleep timing, particularly later midpoint of sleep, has been linked to emotion dysregulation and psychopathology. Prior adult studies link poor sleep (e.g., shorter duration, later midpoint), to altered resting-state functional connectivity (rs-FC) within and between key neurocognitive networks, particularly the default mode network (DMN), which is involved in internal thought and rumination. Importantly, many psychiatric disorders begin during adolescence, a period of shifted sleep schedules. We explored associations between midpoint of sleep and rs-FC of the DMN and other core neurocognitive networks in youth. Sleep timing was measured in 3,798 youth (11.9±0.6 years, 47.5% female) from the Adolescent Brain Cognitive Development study using Fitbit watches (over 13.1±6.5 days). Internalizing symptoms were measured using self-report and rs-FC was measured between the DMN and three neurocognitive networks: dorsal attention network (DAN), frontoparietal network (FPN), and salience network (SN). Associations between sleep timing and rs-FC were measured using linear regressions adjusting for age, sex, race, parental education, family income, puberty, and head motion. Average midpoint of sleep was 3:35 AM (range: 12:34 AM-11:27 PM). Later midpoint of sleep was associated with increased self-reported depressive symptoms. Later midpoint of sleep was associated with lower DMN-DAN rs-FC. There were no associations between midpoint of sleep and DMN-DMN, DMN-FPN, or DMN-SN network rs-FC. These results add to and extend prior studies in youth by incorporating objective measures of sleep timing (Fitbit data), and in a large national sample. Additionally, our findings may have implications for the consideration of sleep timing when designing behavioral-health interventions in youth

The German Submarine Cables and United States Diplomacy, 1914-1927

Immediately after the outbreak of the World War, Great Britain, France and Japan cut the German submarine cables which were situated in the different oceans of the world. The study of the submarine cables during the World War and its aftermath is a complex problem. To understand the post-war negotiations, previous international agreements, treaties and the ownership, operation and financing of the cables must be understood

Specific leaf area and leaf area index in developing stands of Fagus sylvatica L. and Picea abies Karst

European beech (Fagus sylvatica L.) and Norway spruce (Picea abies Karst.) are two of the most ecologically and economically important forest tree species in Europe. These two species co-occur in many locations in Europe, leading to direct competition for canopy space. Foliage characteristics of two naturally regenerated pure stands of beech and spruce with fully closed canopies were contrasted to assess the dynamic relationship between foliage adaptability to shading, stand LAI and tree growth. We found that individual leaf size is far more conservative in spruce than in beech. Individual leaf and needle area was larger at the top than at the bottom of the canopy in both species. Inverse relationship was found for specific leaf area (SLA), highest SLA values were found at lowest light availability under the canopy. There was no difference in leaf area index (LAI) between the two stands, however LAI increased from 10.8 to 14.6 m2m-2 between 2009 and 2011. Dominant trees of both species were more efficient in converting foliage mass or area to produce stem biomass, although this relationship changed with age and was species-specific. Overall, we found larger foliage plasticity in beech than in spruce in relation to light conditions, indicating larger capacity to exploit niche openings

Attention, attention! Posttraumatic stress disorder is associated with altered attention-related brain function

Posttraumatic stress disorder (PTSD) is a debilitating condition characterized by altered arousal, mood, and cognition. Studies report attentional alterations such as threat bias in individuals with PTSD, though this work has largely been conducted within emotionally-charged contexts (e.g., threatening stimuli). Emerging behavioral evidence suggests that PTSD-related attention deficits exist even in the absence of threatening cues or anxiety triggers. However, the role and functioning of attention brain circuits as they relate to PTSD remains underexplored. In this mini review, we highlight recent work using non-emotional stimuli to investigate the neurobiology of attention and disruptions to attention-related brain function among individuals with PTSD. We then discuss gaps in the current literature, including questions pertaining to the neural circuitry of attentional alterations in PTSD, as well as the contributions that trauma exposure, PTSD symptoms, comorbidities, and pre-existing vulnerabilities may have in this relationship. Finally, we suggest future directions for this emerging area of research, which may further inform knowledge surrounding the neurobiological underpinnings of PTSD and potential treatments

Fe-EDTA-Bisamide and Fe-ADR-925, The Iron-Bound Hydrolysis Product of the Cardioprotective Agent Dexrazoxane, Cleave DNA Via the Hydroxyl Radical

Use of the antitumor drug doxorubicin is limited by cardiomyopathic side-effects which are believed to be due to iron-mediated hydroxyl radical generation. Dexrazoxane reduces this cardiotoxicity, possibly by removal of iron from doxorubicin by the EDTA-like hydrolysis product of dexrazoxane, ADR-925. However, EDTA-diimides like dexrazoxane, previously used as antitumor agents, are themselves carcinogenic, and recent studies have found that Fe-ADR-925 can also promote hydroxyl radical production. This study demonstrates that, like Fe-EDTA, Fe-ADR-925 and a related desmethyl complex can cleave plasmid DNA under Fenton conditions, and suggests by radical scavenger study that this cleavage is probably via the hydroxyl radical. Differences in DNA cleavage dependence upon concentrations of Fe-EDTA, Fe-ADR-925 and Fe-EDTA-bisamide can be explained by differences in the solution chemistry of the complexes

A virtual reality martial arts-based intervention reduces pain, drug craving, and stress in patients with opioid use disorder

Background: Some individuals with opioid use disorder (OUD) report high levels of pain, anxiety, stress and drug craving that may occasion relapse, reduce adherence to treatment, and reduce quality of life. This pilot study evaluated whether a novel martial arts-based intervention can lower self-reported and physiological markers of pain, anxiety, stress and opioid craving in individuals with OUD undergoing methadone maintenance treatment (MMT). Methods: 15 MMT patients (11 females) completed a 12-week ‘Heroes Circle’ intervention that involved twice-weekly 30-min sessions centering around martial arts-based breathing and meditative techniques using therapist-assisted virtual reality (VR). Patients self-reported on five measures (pain, drug craving, anxiety, depression, anger) using a 0-10 scale before (pre) and after (post) each session. Salivary markers of inflammation (C-reactive protein [CRP]) and stress (cortisol) were collected before and after several sessions (baseline, weeks 4, 8, and 12). Results: There were significant pre-post session reductions in rated pain, drug craving, anxiety and depression, and saliva cortisol (ps\u3c0.05). For opioid craving, there was also an effect of week such that craving decreased from weeks 1-6, increased from 7-9, and decreased again from 10-12 (ps\u3c0.05); there was also a session x week interaction such that the pre-post reduction in craving reached significance in weeks 1-3 only. There were no significant main effects or interactions for anger or CRP (ps\u3e0.05). Conclusions: These preliminary results suggest VR-based, martial-arts meditative intervention is a promising approach for reducing pain, anxiety, stress and craving levels among individuals with OUD. Further controlled studies are warranted