Publications by authors named "Victoria C Smith"

27 Publications

  • Page 1 of 1

A revised AMS and tephra chronology for the Late Middle to Early Upper Paleolithic occupations of Ortvale Klde, Republic of Georgia.

J Hum Evol 2021 Feb 25;151:102908. Epub 2020 Dec 25.

Department of Anthropology, University of Connecticut, CT, USA. Electronic address:

The nature and timing of the shift from the Late Middle Paleolithic (LMP) to the Early Upper Paleolithic (EUP) varied geographically, temporally, and substantively across the Near East and Eurasia; however, the result of this process was the archaeological disappearance of Middle Paleolithic technologies across the length and breadth of their geographic distribution. Ortvale Klde rockshelter (Republic of Georgia) contains the most detailed LMP-EUP archaeological sequence in the Caucasus, an environmentally and topographically diverse region situated between southwest Asia and Europe. Tephrochronological investigations at the site reveal volcanic ash (tephra) from various volcanic sources and provide a tephrostratigraphy for the site that will facilitate future correlations in the region. We correlate one of the cryptotephra layers to the large, caldera-forming Nemrut Formation eruption (30,000 years ago) from Nemrut volcano in Turkey. We integrate this tephrochronological constraint with new radiocarbon dates and published ages in an OxCal Bayesian age model to produce a revised chronology for the site. This model increases the ages for the end of the LMP (∼47.5-44.2 ka cal BP) and appearance of the EUP (∼46.7-43.6 ka cal BP) at Ortvale Klde, which are earlier than those currently reported for other sites in the Caucasus but similar to estimates for specific sites in southwest Asia and eastern Europe. These data, coupled with archaeological, stratigraphic, and taphonomic observations, suggest that at Ortvale Klde, (1) the appearance of EUP technologies of bone and stone has no technological roots in the preceding LMP, (2) a LMP population vacuum likely preceded the appearance of these EUP technologies, and (3) the systematic combination of tephra correlations and absolute dating chronologies promises to substantially improve our inter-regional understanding of this critical time interval of human evolution and the potential interconnectedness of hominins at different sites.
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http://dx.doi.org/10.1016/j.jhevol.2020.102908DOI Listing
February 2021

The magnitude and impact of the 431 CE Tierra Blanca Joven eruption of Ilopango, El Salvador.

Proc Natl Acad Sci U S A 2020 10 28;117(42):26061-26068. Epub 2020 Sep 28.

Gerencia de Geología del Observatorio Ambiental, Ministerio de Medio Ambiente y Recursos Naturales, San Salvador 76230, El Salvador.

The Tierra Blanca Joven (TBJ) eruption from Ilopango volcano deposited thick ash over much of El Salvador when it was inhabited by the Maya, and rendered all areas within at least 80 km of the volcano uninhabitable for years to decades after the eruption. Nonetheless, the more widespread environmental and climatic impacts of this large eruption are not well known because the eruption magnitude and date are not well constrained. In this multifaceted study we have resolved the date of the eruption to 431 ± 2 CE by identifying the ash layer in a well-dated, high-resolution Greenland ice-core record that is >7,000 km from Ilopango; and calculated that between 37 and 82 km of magma was dispersed from an eruption coignimbrite column that rose to ∼45 km by modeling the deposit thickness using state-of-the-art tephra dispersal methods. Sulfate records from an array of ice cores suggest stratospheric injection of 14 ± 2 Tg S associated with the TBJ eruption, exceeding those of the historic eruption of Pinatubo in 1991. Based on these estimates it is likely that the TBJ eruption produced a cooling of around 0.5 °C for a few years after the eruption. The modeled dispersal and higher sulfate concentrations recorded in Antarctic ice cores imply that the cooling would have been more pronounced in the Southern Hemisphere. The new date confirms the eruption occurred within the Early Classic phase when Maya expanded across Central America.
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http://dx.doi.org/10.1073/pnas.2003008117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584997PMC
October 2020

Identification of GSK3186899/DDD853651 as a Preclinical Development Candidate for the Treatment of Visceral Leishmaniasis.

J Med Chem 2019 02 20;62(3):1180-1202. Epub 2018 Dec 20.

Global Health R&D , GlaxoSmithKline , Calle Severo Ochoa, 2 , 28760 Tres Cantos , Madrid Spain.

The leishmaniases are diseases that affect millions of people across the world, in particular visceral leishmaniasis (VL) which is fatal unless treated. Current standard of care for VL suffers from multiple issues and there is a limited pipeline of new candidate drugs. As such, there is a clear unmet medical need to identify new treatments. This paper describes the optimization of a phenotypic hit against Leishmania donovani, the major causative organism of VL. The key challenges were to balance solubility and metabolic stability while maintaining potency. Herein, strategies to address these shortcomings and enhance efficacy are discussed, culminating in the discovery of preclinical development candidate GSK3186899/DDD853651 (1) for VL.
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http://dx.doi.org/10.1021/acs.jmedchem.8b01218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407917PMC
February 2019

Outcomes of early parent-child adrenocortical attunement in the high-risk offspring of depressed parents.

Dev Psychobiol 2018 05 12;60(4):468-482. Epub 2018 Mar 12.

Department of Psychology, University of Maryland, College Park, Maryland.

This study examined the impact of parent-child attunement of morning cortisol on parenting and child outcomes in dyads with and without parental depression. Participants included 142 parent-child dyads (3-5 years-old) who provided morning cortisol samples at Wave 1, and 98 dyads returned for the 3-year follow-up at Wave 2. Results indicated that for parents with a history of depression and for female children, stronger attunement predicted increases in parental hostility from Wave 1 to Wave 2. For females only, stronger attunement was related to children's depressive symptoms at Wave 1 and Wave 2. Stronger attunement was also associated with increases in children's depressive symptoms from Wave 1 to Wave 2, poorer psychosocial functioning at Wave 1, and ADHD symptoms at Wave 2. Findings highlight attunement as an important biological process related to parenting and child outcomes and suggest it may play a role in the intergenerational transmission of depression risk.
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http://dx.doi.org/10.1002/dev.21623DOI Listing
May 2018

Design and Synthesis of Brain Penetrant Trypanocidal N-Myristoyltransferase Inhibitors.

J Med Chem 2017 12 22;60(23):9790-9806. Epub 2017 Nov 22.

Drug Discovery Unit, College of Life Sciences, University of Dundee , Sir James Black Centre, Dundee DD1 5EH, U.K.

N-Myristoyltransferase (NMT) represents a promising drug target within the parasitic protozoa Trypanosoma brucei (T. brucei), the causative agent for human African trypanosomiasis (HAT) or sleeping sickness. We have previously validated T. brucei NMT as a promising druggable target for the treatment of HAT in both stages 1 and 2 of the disease. We report on the use of the previously reported DDD85646 (1) as a starting point for the design of a class of potent, brain penetrant inhibitors of T. brucei NMT.
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http://dx.doi.org/10.1021/acs.jmedchem.7b01255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734605PMC
December 2017

Replicate in Bone Marrow-Derived CD11c Cells but Not in Dendritic Cells Isolated from the Murine Gastrointestinal Tract.

J Immunol 2017 12 20;199(11):3789-3797. Epub 2017 Oct 20.

Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536

Recent fate-mapping studies and gene-expression profiles suggest that commonly used protocols to generate bone marrow-derived cultured dendritic cells yield a heterogeneous mixture, including some CD11c cells that may not have a bona fide counterpart in vivo. In this study, we provide further evidence of the discordance between ex vivo-isolated and in vitro-cultured CD11c cells by analyzing an additional phenotype, the ability to support cytosolic growth of the facultative intracellular bacterial pathogen Two days after foodborne infection of mice with GFP-expressing , a small percentage of CD103 and CD103 conventional dendritic cells (cDC) in the intestinal lamina propria and mesenteric lymph nodes were GFP However, in vitro infection of the same subsets of cells harvested from naive mice resulted in inefficient invasion by the bacteria (<0.1% of the inoculum). The few intracellular bacteria detected survived for only a few hours. In contrast, cultured CD103CD11c cells induced by GM-CSF readily supported exponential growth of Flt3 ligand-induced cultures yielded CD103CD11c cells that more closely resembled cDC, with only a modest level of replication. For both culture protocols, the longer the cells were maintained in vitro, the more readily they supported intracellular growth. The results of this study suggest that cDC are not a niche for intracellular growth of during intestinal infection of mice.
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http://dx.doi.org/10.4049/jimmunol.1700970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698106PMC
December 2017

Discovery and Optimization of 5-Amino-1,2,3-triazole-4-carboxamide Series against Trypanosoma cruzi.

J Med Chem 2017 09 27;60(17):7284-7299. Epub 2017 Aug 27.

Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee , Sir James Black Centre, Dundee DD1 5EH, U.K.

Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, is the most common cause of cardiac-related deaths in endemic regions of Latin America. There is an urgent need for new safer treatments because current standard therapeutic options, benznidazole and nifurtimox, have significant side effects and are only effective in the acute phase of the infection with limited efficacy in the chronic phase. Phenotypic high content screening against the intracellular parasite in infected VERO cells was used to identify a novel hit series of 5-amino-1,2,3-triazole-4-carboxamides (ATC). Optimization of the ATC series gave improvements in potency, aqueous solubility, and metabolic stability, which combined to give significant improvements in oral exposure. Mitigation of a potential Ames and hERG liability ultimately led to two promising compounds, one of which demonstrated significant suppression of parasite burden in a mouse model of Chagas' disease.
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http://dx.doi.org/10.1021/acs.jmedchem.7b00463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601362PMC
September 2017

Parental depression and parent and child stress physiology: Moderation by parental hostility.

Dev Psychobiol 2017 12 23;59(8):997-1009. Epub 2017 Aug 23.

Department of Psychology, University of Maryland, College Park, Maryland.

This study examined the moderating role of parental hostility on the associations between parental depression and the cortisol awakening response (CAR) and morning cortisol levels of both parents and children. 148 parents and 148 preschool-aged children provided salivary cortisol samples at waking, 30 and 45 min post-waking on two consecutive days. Parental depression was assessed using a clinical interview, and parental hostility was assessed using an observational parent-child interaction task. Results indicated that the combination of parental lifetime depression and high parental hostility was associated with lower morning cortisol levels in both parents and children. This interactive effect was present in children regardless of their exposure to parental depression. In addition, the combination of higher levels of parents' current depressive symptoms and parental hostility was associated with lower parent CAR. Lastly, parents' and children's lower morning cortisol levels were associated with parent-reported child externalizing symptoms. Findings demonstrate that parents and children have similar stress system functioning related to parental depression and the parenting context, as well as children's behavioral problems, which may play a role in the intergenerational transmission of risk for psychopathology.
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http://dx.doi.org/10.1002/dev.21556DOI Listing
December 2017

Stability and Predictive Validity of the Parent-Child Sleep Interactions Scale: A Longitudinal Study Among Preschoolers.

J Clin Child Adolesc Psychol 2018 May-Jun;47(3):382-396. Epub 2017 Aug 17.

a Department of Psychology , University of Maryland.

Little research has examined the processes underlying children's persistent sleep problems and links with later psychopathology. The current study examined the stability of parent-child sleep interactions as assessed with the parent-reported Parent-Child Sleep Interactions Scale (PSIS) and examined whether sleep interactions in preschool-age children predict sleep problems and psychiatric symptoms later in childhood. Participants included 108 preschool-age children (50% female) and their parents. Parents completed the PSIS when children were 3-5 years (T1) and again when they were 6-9 years (T2). The PSIS includes three subscales-Sleep Reinforcement (reassurance of child sleep behaviors), Sleep Conflict (parent-child conflict at bedtime), Sleep Dependence (difficulty going to sleep without parent)-and a total score. Higher scores indicate more problematic bedtime interactions. Children's sleep problems and psychiatric symptoms at T1 and T2 were assessed with a clinical interview. PSIS scores were moderately stable from T1 to T2, and the factor structure of the PSIS remained relatively consistent over time. Higher total PSIS scores at T1 predicted increases in children's sleep problems at T2. Higher PSIS Sleep Conflict scores at T1 predicted increases in oppositional defiant disorder symptoms at T2. Children with more sleep problems and higher PSIS Sleep Reinforcement scores at T1 showed increases in attention deficit/hyperactivity disorder, depressive, and anxiety symptoms at T2. These findings provide evidence for the predictive validity of the PSIS and highlight the importance of early parent-child sleep interactions in the development of sleep and psychiatric symptoms in childhood. Parent-child sleep interactions may serve as a useful target for interventions.
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http://dx.doi.org/10.1080/15374416.2017.1357125DOI Listing
May 2019

Exacerbation of alopecia areata: A possible complication of sodium tetradecyl sulphate foam sclerotherapy treatment for varicose veins.

SAGE Open Med Case Rep 2017 2;5:2050313X17712643. Epub 2017 Jun 2.

Absolute Aesthetics, Guildford, UK.

A 40-year-old woman with a history of alopecia areata related to stress or hormonal changes was treated for bilateral primary symptomatic varicose veins (CEAP clinical score C2S) of pelvic origin, using a staged procedure. Her first procedure entailed pelvic vein embolisation of three pelvic veins using 14 coils and including foam sclerotherapy of the tributaries, using 3% sodium tetradecyl sulphate. Following this procedure, she had an exacerbation of alopecia areata with some moderate shedding of hair. Subsequently, she underwent endovenous laser ablation under local anaesthetic without incident. Seven months after the pelvic vein embolisation, she underwent foam sclerotherapy of leg and labial varicose veins using sodium tetradecyl sulphate. Two days following this procedure, she had a severe exacerbation of alopecia areata with gross shedding of hair. These two episodes of exacerbation of alopecia areata appear to be associated with sodium tetradecyl sulphate foam sclerotherapy of veins.
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http://dx.doi.org/10.1177/2050313X17712643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459345PMC
June 2017

Parent-child adrenocortical concordance in early childhood: The moderating role of parental depression and child temperament.

Biol Psychol 2017 03 29;124:100-110. Epub 2017 Jan 29.

University of Maryland College Park, USA. Electronic address:

This study examined biological concordance between parent and child morning cortisol and whether parent and child-level risk factors for depression moderated this association. Participants included 136 parents and their preschool-aged children. Parents and children obtained salivary cortisol samples at waking, and 30 and 45min post-waking across two days to assess the cortisol awakening response. Parental lifetime depression was assessed using a clinical interview and child temperamental negative emotionality (NE) and positive emotionality (PE) were assessed using an observational laboratory-based assessment. Results indicated significant parent-child concordance between both average cortisol levels and cortisol fluctuations across waking. Greater concordance was observed for dyads with parents with a lifetime history of depression and with children high in NE and PE. These parent- and child-level moderators were associated with different indices of concordance. Findings highlight the need to examine the role of parent and child risk factors for depression on parent-child adrenocortical concordance.
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http://dx.doi.org/10.1016/j.biopsycho.2017.01.013DOI Listing
March 2017

Magma reservoir dynamics at Toba caldera, Indonesia, recorded by oxygen isotope zoning in quartz.

Sci Rep 2017 01 25;7:40624. Epub 2017 Jan 25.

Department of Geological Sciences, University of Oregon, Oregon, USA.

Quartz is a common phase in high-silica igneous rocks and is resistant to post-eruptive alteration, thus offering a reliable record of magmatic processes in silicic magma systems. Here we employ the 75 ka Toba super-eruption as a case study to show that quartz can resolve late-stage temporal changes in magmatic δO values. Overall, Toba quartz crystals exhibit comparatively high δO values, up to 10.2‰, due to magma residence within, and assimilation of, local granite basement. However, some 40% of the analysed quartz crystals display a decrease in δO values in outermost growth zones compared to their cores, with values as low as 6.7‰ (maximum ∆ = 1.8‰). These lower values are consistent with the limited zircon record available for Toba, and the crystallisation history of Toba quartz traces an influx of a low-δO component into the magma reservoir just prior to eruption. Here we argue that this late-stage low-δO component is derived from hydrothermally-altered roof material. Our study demonstrates that quartz isotope stratigraphy can resolve magmatic events that may remain undetected by whole-rock or zircon isotope studies, and that assimilation of altered roof material may represent a viable eruption trigger in large Toba-style magmatic systems.
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http://dx.doi.org/10.1038/srep40624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264179PMC
January 2017

Children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood.

Dev Psychobiol 2016 12 2;58(8):1019-1033. Epub 2016 Jun 2.

Department of Psychology, University of Maryland College Park, College Park, Maryland.

This study examined the stability of children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood. Ninety-six children (51 males) completed stress-inducing laboratory tasks and provided five salivary cortisol samples in early (W1) and middle (W2) childhood. Although W1 cortisol responses did not predict W2 cortisol responses, children's cortisol responses demonstrated change: compared to their W1 cortisol responses, children's W2 cortisol responses demonstrated an increased slope and more negative quadratic curvature. Furthermore, child psychiatric symptoms at W1 moderated the stability of children's cortisol responses. Children with fewer preschool psychiatric symptoms demonstrated greater inter-individual and intra-individual stability, whereas children with higher preschool psychiatric symptoms and comorbidity demonstrated systematic inter-individual and intra-individual instability in cortisol responses over time. Findings suggest a developmental shift toward increasing cortisol stress responses from early to middle childhood and highlight preschool psychopathology as a moderator of stability in children's cortisol responses over time.
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http://dx.doi.org/10.1002/dev.21435DOI Listing
December 2016

Upstream or downstream?

Authors:
Victoria C Smith

Med J Aust 2015 Nov;203(10):412-3.e1

Monash University, Melbourne, VIC

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http://dx.doi.org/10.5694/mja15.00718DOI Listing
November 2015

Physiological and Behavioral Vulnerability Markers Increase Risk to Early Life Stress in Preschool-Aged Children.

J Abnorm Child Psychol 2016 07;44(5):859-70

Department of Psychology, University of Maryland, College Park, MD, 20742, USA.

The study examined whether child physiological (cortisol reactivity) and behavioral (negative emotionality) risk factors moderate associations between the early rearing environment, as measured by child exposure to maternal depression and stressful life events, and preschool psychopathology and psychosocial functioning. A sample of 156 preschool-aged children (77 boys, 79 girls; age M = 49.80 months, SD = 9.57, range: 36-71) participated in an observational assessment of temperament and was exposed to a stress-inducing laboratory task, during which we obtained five salivary cortisol samples. Parents completed clinical interviews to assess child and parent psychopathology and stressful life events. Results indicated that the combination of a blunted pattern of cortisol reactivity and recent stressful life events was associated with higher levels of preschoolers' externalizing symptoms and lower psychosocial functioning. In addition, greater life stress was associated with higher levels of preschoolers' internalizing symptoms. Lastly, children with high levels of negative emotionality and who were exposed to maternal depression had the lowest social competence. Our findings highlight the critical role of the early environment, particularly for children with identified risk factors, and add to our understanding of pathways involved in early emerging psychopathology and impairment.
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http://dx.doi.org/10.1007/s10802-015-0087-7DOI Listing
July 2016

Preschool irritability predicts child psychopathology, functional impairment, and service use at age nine.

J Child Psychol Psychiatry 2015 Sep 27;56(9):999-1007. Epub 2015 Feb 27.

Department of Psychology, Stony Brook University, Stony Brook, NY, USA.

Background: Little is known about the predictive validity and clinical significance of chronic irritability during early childhood. This prospective, longitudinal study examined associations of preschool chronic irritability with psychiatric disorders, functional impairment, and service use at age nine in a large community sample.

Methods: Four hundred and forty-six children were assessed at age three and again at age nine. Child psychopathology and functional impairment were assessed at age three with the Preschool Age Psychiatric Assessment (PAPA) with parents and at age nine with the Kiddie-Schedule of Affective Disorders and Schizophrenia (K-SADS) with parents and children. Items from the PAPA were used to create a dimensional measure of chronic irritability at age three. At age nine, mothers, fathers, and youth completed the Child Depression Inventory (CDI) and the Screen for Anxiety Related Disorders (SCARED).

Results: Chronic irritability at age three predicted any current and lifetime anxiety disorders at age nine, current and lifetime generalized anxiety disorder, and current separation anxiety, after controlling for baseline anxiety disorders. In addition, preschool irritability predicted increases in anxiety and disruptive behavior disorder symptoms on the K-SADS, and maternal and paternal reports of depressive and anxiety symptoms on the CDI and SCARED. Lastly, preschool irritability predicted greater functional impairment and outpatient treatment use, even after controlling for all psychiatric disorders at baseline.

Conclusions: Findings underscore the central role of irritability in developmental psychopathology and support the importance of early detection and interventions targeting preschool irritability.
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http://dx.doi.org/10.1111/jcpp.12403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531384PMC
September 2015

"It takes two": the interaction between parenting and child temperament on parents' stress physiology.

Dev Psychobiol 2015 Apr 18;57(3):336-48. Epub 2015 Mar 18.

Department of Psychology, University of Maryland, College Park, 20742, MD.

The biological basis of parenting has received recent attention given the profound effects of parenting on both child and parent health outcomes. This study examined the moderating role of child temperamental effortful control on the association between observed parental hostility and parents' cortisol awakening response (CAR), a critical index of stress system functioning. Participants included 149 parents and their preschool-aged children. Parents obtained salivary cortisol samples at waking, and 30 and 45 min post-waking across two consecutive days. Parental hostility was assessed during an observational parent-child interaction task, and child effortful control was assessed using parent report. Parental hostility was associated with parents' lower cortisol levels at 30 and 45 min post-waking and lower CAR. Moreover, results demonstrated an interaction between parenting and child temperament on parent CAR. The findings highlight the need to examine the interplay between parenting and child temperament on parents' stress physiology.
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http://dx.doi.org/10.1002/dev.21301DOI Listing
April 2015

Lead optimization of a pyrazole sulfonamide series of Trypanosoma brucei N-myristoyltransferase inhibitors: identification and evaluation of CNS penetrant compounds as potential treatments for stage 2 human African trypanosomiasis.

J Med Chem 2014 Dec 20;57(23):9855-69. Epub 2014 Nov 20.

Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee , Sir James Black Centre, Dundee DD1 5EH, U.K.

Trypanosoma brucei N-myristoyltransferase (TbNMT) is an attractive therapeutic target for the treatment of human African trypanosomiasis (HAT). From previous studies, we identified pyrazole sulfonamide, DDD85646 (1), a potent inhibitor of TbNMT. Although this compound represents an excellent lead, poor central nervous system (CNS) exposure restricts its use to the hemolymphatic form (stage 1) of the disease. With a clear clinical need for new drug treatments for HAT that address both the hemolymphatic and CNS stages of the disease, a chemistry campaign was initiated to address the shortfalls of this series. This paper describes modifications to the pyrazole sulfonamides which markedly improved blood-brain barrier permeability, achieved by reducing polar surface area and capping the sulfonamide. Moreover, replacing the core aromatic with a flexible linker significantly improved selectivity. This led to the discovery of DDD100097 (40) which demonstrated partial efficacy in a stage 2 (CNS) mouse model of HAT.
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http://dx.doi.org/10.1021/jm500809cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269550PMC
December 2014

Construct validity of the parent-child sleep interactions scale (PSIS): associations with parenting, family stress, and maternal and child psychopathology.

Sleep Med 2014 Aug 2;15(8):942-51. Epub 2014 May 2.

Department of Psychology, University of Maryland, College Park, MD 20742, USA.

Study Objectives: Using a multi-method design, this study examined the construct validity of the Parent-Child Sleep Interactions Scale (PSIS; Alfano et al., 2013), which measures sleep-related parenting behaviors and interactions that contribute to preschoolers' sleep problems.

Methods: Participants included a community sample of 155 preschoolers (ages 3-5years; 51.6% female). Primary caregivers completed the PSIS. Parenting styles and behaviors were assessed with laboratory observations and parent reports. Parent and child psychopathology and family life stress were assessed with clinical interviews and parent reports.

Results: Bivariate correlations revealed significant associations between the PSIS and a number of variables, including lower observed parental support and quality of instruction; higher observed parental intrusiveness; authoritative, authoritarian, and permissive parenting styles; current maternal depressive and/or anxiety disorders and depressive symptomatology; increased stressful life events; lower marital satisfaction; and higher child depressive, anxiety, attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD) symptoms. The patterns of association varied based on the specific PSIS scale.

Conclusions: The PSIS demonstrates meaningful associations with parenting, maternal psychopathology, family stress, and child psychopathology and functioning. Findings suggest that the PSIS is a valid measure for assessing sleep-related parent/child behaviors and interactions among preschoolers, suited to real-world settings.
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http://dx.doi.org/10.1016/j.sleep.2014.04.002DOI Listing
August 2014

Preschool irritability: longitudinal associations with psychiatric disorders at age 6 and parental psychopathology.

J Am Acad Child Adolesc Psychiatry 2013 Dec 26;52(12):1304-13. Epub 2013 Sep 26.

University of Maryland-College Park. Electronic address:

Objective: There is increasing scientific and clinical attention to chronic irritability in youth. However, little is known about the predictive validity and clinical significance of chronic irritability during early childhood. This prospective, longitudinal study examined associations of chronic irritability with psychiatric disorders and parental psychopathology in a large community sample of preschoolers.

Method: Four hundred sixty-two preschool-age children were assessed at 3 and 6 years of age. Child psychopathology was assessed at baseline (3 years) and follow-up (6 years) using a diagnostic interview, the Preschool Age Psychiatric Assessment, with parents. Items from the Preschool Age Psychiatric Assessment were used to create a dimensional measurement of chronic irritability. Parental psychopathology was assessed with a diagnostic interview at baseline.

Results: Chronic irritability was concurrently associated with a wide range of psychiatric disorders and functional impairment at 3 and 6 years of age. Irritability at 3 years predicted depression, oppositional defiant disorder, and functional impairment at 6 years after controlling for baseline disorders. Irritability also was associated with parental depression and anxiety.

Conclusions: Findings underscore the central role of irritability in early-emerging mental health problems. They are consistent with longitudinal studies in older youth indicating that chronic irritability predicts later depression and anxiety and support the importance of early detection and interventions targeting preschool irritability.
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http://dx.doi.org/10.1016/j.jaac.2013.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3860177PMC
December 2013

The Parent-Child Sleep Interactions Scale (PSIS) for preschoolers: factor structure and initial psychometric properties.

J Clin Sleep Med 2013 Nov 15;9(11):1153-60. Epub 2013 Nov 15.

Department of Psychology, University of Houston, Houston, TX.

Study Objectives: Given the high prevalence of sleep problems in early childhood and the significant impact of parenting on children's sleep, the current study aimed to determine the factor structure and psychometric properties of a new measure for assessing sleep-related parenting behaviors and interactions among preschool-aged children-The Parent-Child Sleep Interactions Scale (PSIS).

Methods: Data was collected among parents of 209 preschool-aged children in two diverse metropolitan areas. All parents completed demographic questionnaires, the Parent-Child Sleep Interaction Scale (PSIS), and the Child Behavior Checklist (CBCL). A subset of parents completed structured interviews using the Preschool Age Psychiatric Assessment (PAPA). Following data reduction procedures, exploratory factor analysis (EFA) using principal axis extraction and oblique rotation was conducted, and internal consistency was assessed. Associations between PSIS scores and sleep problems based on the CBCL and PAPA as well as child sleep problems during infancy were examined. Differences based on demographic variables including race/ethnicity were also investigated.

Results: EFA revealed a three-factor solution explaining 60% of the variance in total PSIS scores. Individual factors based on 12 items were labeled Sleep Reinforcement, Sleep Conflict, and Sleep Dependence. Internal consistency for all subscales and total PSIS scores was acceptable. PSIS subscales were positively correlated with both CBCL and PAPA Sleep Problems. Sleep problems during the first year of life were associated with Sleep Conflict and total PSIS scores. Significant differences in PSIS scores based on race/ ethnicity were found.

Conclusions: The PSIS shows promise as a valid measure of sleep-related parent/child behaviors and interactions among preschoolers.
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http://dx.doi.org/10.5664/jcsm.3156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3805800PMC
November 2013

Noisy spit: parental noncompliance with child salivary cortisol sampling.

Dev Psychobiol 2014 May 10;56(4):647-56. Epub 2013 Jun 10.

Department of Psychology, University of Maryland, College Park, MD, 20742.

Studies assessing hypothalamic-pituitary-adrenal (HPA) axis functioning in young children commonly involve parental collection of salivary cortisol in ambulatory settings. However, no data are available on the compliance of parents in collecting ambulatory measures of children's salivary cortisol. This study examined the effects of parental compliance on the cortisol awakening response (CAR) and diurnal cortisol slopes in a sample of preschool-age children (ages 3-5). Eighty-one parents were instructed to collect their child's salivary cortisol samples upon their child's waking, 30 and 45 min post-waking and before bedtime on two weekdays. Subjective parental compliance was assessed using parent-report, and objective parental compliance was assessed using an electronic monitoring device. Rates of compliance were higher based on parent-report than electronic monitoring. Parental noncompliance as indicated by electronic monitoring was associated with higher waking cortisol and lower CAR. Findings suggest the need to incorporate electronic monitoring of parental compliance into developmental neuroendocrine research, especially when assessing the CAR.
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http://dx.doi.org/10.1002/dev.21133DOI Listing
May 2014

Early exposure to parental depression and parenting: associations with young offspring's stress physiology and oppositional behavior.

J Abnorm Child Psychol 2013 Nov;41(8):1299-310

Department of Psychology, University of Maryland College Park, College Park, MD, 20742, USA,

Hypothalamic-pituitary-adrenal (HPA) axis reactivity to stress is posited to play a role in the intergenerational transmission of risk for psychopathology and other negative outcomes in the offspring of depressed parents. We tested the hypothesis that the joint, interactive effects of exposure to parental depression during early childhood and parental hostility impact the development of young children's stress physiology and early emerging behavior problems. A sample of 165 preschool-age children (81 boys, 84 girls), of whom 103 had a parent with a history of depression, was exposed to a stress-inducing laboratory task, and five salivary cortisol samples were obtained. Parents completed clinical interviews and an observational parent-child interaction task. We found that the offspring exposed to maternal depression during early childhood and whose parents displayed hostile parenting behaviors during an observational task evidenced high and increasing cortisol levels in response to a laboratory stressor. In addition, the total amount of exposure to maternal depression over the child's life exerted a dose-response effect on the positive relation between parental hostility and child observed oppositional behavior. This study underscores the importance of the early rearing environment on young children's stress physiology and early emerging behavior problems.
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http://dx.doi.org/10.1007/s10802-013-9763-7DOI Listing
November 2013

Maternal psychopathology and early child temperament predict young children's salivary cortisol 3 years later.

J Abnorm Child Psychol 2013 May;41(4):531-42

Department of Psychology, University of Maryland, College Park, MD 20742, USA.

Neuroendocrine dysfunction is hypothesized to be an early emerging vulnerability marker for depression. We tested whether the main and interactive effects of maternal psychopathology and early child temperamental vulnerability for depression assessed at age three predicted offspring's basal cortisol function at age 6 years. 228 (122 males) children participated in the baseline and follow-up assessments. At age three, maternal lifetime psychopathology was assessed with a diagnostic clinical interview, and child temperamental positive affectivity (PA) and negative affectivity (NA) were assessed using laboratory observations. At age six, children's waking and evening cortisol were assessed on 2 days. Maternal lifetime anxiety predicted offspring's higher morning cortisol at age six. Child temperamental NA at age three predicted higher evening cortisol at age six. There was a significant interaction between maternal lifetime depression and child temperamental PA at age three in predicting offspring's morning cortisol at age six. For the offspring of mothers with lifetime depression, higher PA at age 3 predicted lower morning cortisol at age 6. These findings highlight the importance of examining the main and interactive effects of maternal psychopathology and early child temperamental vulnerability in predicting the development of offspring's stress physiology. Findings hold significance in identifying etiological mechanisms of risk and delineating the complex developmental pathways to psychopathology.
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http://dx.doi.org/10.1007/s10802-012-9703-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874814PMC
May 2013

Volcanic ash layers illuminate the resilience of Neanderthals and early modern humans to natural hazards.

Proc Natl Acad Sci U S A 2012 Aug 23;109(34):13532-7. Epub 2012 Jul 23.

Department of Geography, Royal Holloway University of London, Surrey, United Kingdom.

Marked changes in human dispersal and development during the Middle to Upper Paleolithic transition have been attributed to massive volcanic eruption and/or severe climatic deterioration. We test this concept using records of volcanic ash layers of the Campanian Ignimbrite eruption dated to ca. 40,000 y ago (40 ka B.P.). The distribution of the Campanian Ignimbrite has been enhanced by the discovery of cryptotephra deposits (volcanic ash layers that are not visible to the naked eye) in archaeological cave sequences. They enable us to synchronize archaeological and paleoclimatic records through the period of transition from Neanderthal to the earliest anatomically modern human populations in Europe. Our results confirm that the combined effects of a major volcanic eruption and severe climatic cooling failed to have lasting impacts on Neanderthals or early modern humans in Europe. We infer that modern humans proved a greater competitive threat to indigenous populations than natural disasters.
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http://dx.doi.org/10.1073/pnas.1204579109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427068PMC
August 2012

Discovery of a novel class of orally active trypanocidal N-myristoyltransferase inhibitors.

J Med Chem 2012 Jan 7;55(1):140-52. Epub 2011 Dec 7.

Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee, DD1 5EH, U.K.

N-Myristoyltransferase (NMT) represents a promising drug target for human African trypanosomiasis (HAT), which is caused by the parasitic protozoa Trypanosoma brucei. We report the optimization of a high throughput screening hit (1) to give a lead molecule DDD85646 (63), which has potent activity against the enzyme (IC(50) = 2 nM) and T. brucei (EC(50) = 2 nM) in culture. The compound has good oral pharmacokinetics and cures rodent models of peripheral HAT infection. This compound provides an excellent tool for validation of T. brucei NMT as a drug target for HAT as well as a valuable lead for further optimization.
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http://dx.doi.org/10.1021/jm201091tDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256935PMC
January 2012

Optimisation of the anti-Trypanosoma brucei activity of the opioid agonist U50488.

ChemMedChem 2011 Oct 10;6(10):1832-40. Epub 2011 Aug 10.

Drug Discovery Unit, College of Life Sciences, James Black Centre, University of Dundee, Dundee, DD1 5EH, Scotland, UK.

Screening of the Sigma-Aldrich Library of Pharmacologically Active Compounds (LOPAC) against cultured Trypanosoma brucei, the causative agent of African sleeping sickness, resulted in the identification of a number of compounds with selective antiproliferative activity over mammalian cells. These included (+)-(1R,2R)-U50488, a weak opioid agonist with an EC(50) value of 59 nM as determined in our T. brucei in vitro assay reported previously. This paper describes the modification of key structural elements of U50488 to investigate structure-activity relationships (SAR) and to optimise the antiproliferative activity and pharmacokinetic properties of this compound.
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http://dx.doi.org/10.1002/cmdc.201100278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229842PMC
October 2011