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Maltreatment adversely impacts the development of children across a host of domains. One way in which maltreatment may exert its deleterious effects is by becoming embedded in the activity of neurophysiological systems that regulate metabolic function. This paper reviews the literature regarding the association between childhood maltreatment and the activity of three systems: the parasympathetic nervous system, the sympathetic nervous system, and the hypothalamic–pituitary–adrenal axis. A particular emphasis is placed on the extent to which the literature supports a common account of activity across these systems under conditions of homeostasis and stress. The paper concludes with an outline of directions for future research and the implications of the literature for policy and practice.
OBJECTIVES/GOALS: To characterize the oncogenic potential of HNSCC cell lines harboring 17 non-canonical PIK3CA mutations. METHODS/STUDY POPULATION: Non-canonical PIK3CA mutant constructs generated via site-directed mutagenesis are subcloned into doxycycline-inducible vector pLVX-Puro. Serum-dependent HNSCC cell line (PCI-52-SD1) is then stably transfected with vectors and undergo doxycycline-induction. Cell survival is determined by depriving cells of fetal bovine serum for 72 hours and quantifying remaining cells with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Cell proliferation and migration is evaluated with colony formation assays and transwell assays respectively. RESULTS/ANTICIPATED RESULTS: To date, the survival behavior of eight non-canonical mutants was assessed. Three mutants – Q75E, V71I, and E970K – exhibited 18.7-26.7% greater survival rate relative to cells transfected with wild-type. Five mutants – R519G, Y606C, W328S, C905S, and M1040I – demonstrated survival rates that differed only by −4.3% to +6.6% relative to wild-type. We hypothesize the three activating mutants that exhibited increased survival will also demonstrate increased cell proliferation and migratory behavior whereas the three neutral mutants will not differ from control. DISCUSSION/SIGNIFICANCE OF IMPACT: Ongoing HNSCC PI3K inhibitor trials could be more effective if all PIK3CA hyperactivation mutations are known. Identifying non-canonical mutation effects could result in greater efficacy if drugs are restricted only to those with activating mutations. CONFLICT OF INTEREST DESCRIPTION: JRG and DEJ are co-inventors of cyclic STAT3 decoy and have financial interests in STAT3 Therapeutics, Inc. STAT3 Therapeutics, Inc. holds an interest in a cyclic STAT3 decoy oligonucleotide. The remaining authors declare no conflicts.
Hagstromite, Pb8Cu2+(Te6+O6)2(CO3)Cl4, (IMA2019-093) is a new tellurate mineral from Otto Mountain near Baker, California, USA. It occurs on quartz in association with cerussite, fuettererite and thorneite. It is a secondary oxidation zone mineral and is presumed to have formed by oxidation of earlier formed tellurides, chalcopyrite and galena. Hagstromite occurs as light yellow–green blades, up to ~100 μm long. Crystals are transparent with adamantine to silky lustre. The mineral is brittle with two cleavages providing splintery fracture; the Mohs hardness is probably between 2 and 3. The calculated density is 7.062 g cm–3. Hagstromite is optically biaxial (+), with calculated indices of refraction for α = 2.045, β = 2.066 and γ = 2.102; 2Vmeas = 76(1)°; and optical orientation X = b, Y = a and Z = c. The Raman spectrum of hagstromite exhibits similarities with those of agaite and thorneite and confirms the presence of CO32–. The electron microprobe analyses provided the empirical formula Pb8.07Cu2+0.98Te6+1.96C1.17Cl3.83O15.34. Hagstromite is orthorhombic, space group Ibam, with a = 23.688(17), b = 9.026(8), c = 10.461(8) Å, V = 2237(3) Å3 and Z = 4. The crystal structure of hagstromite (R1 = 0.0659 for 284 I > 2σI reflections) contains a novel Cu2+Te6+2O12 chain assembled of corner-sharing Cu2+O4 squares and Te6+O6 octahedra. The O atoms in the chains form bonds with Pb2+ cations, which in turn bond to Cl– and CO32– anions, thereby creating a framework structure.
Cuyaite (IMA2019-126), Ca2Mn3+As3+14O24Cl, is a new arsenite mineral from near Cuya in the Camarones Valley, Arica Province, Chile. It is associated with anhydrite, native arsenic, arsenolite, calcite, claudetite, ferrinatrite, gajardoite-3R, leiteite, magnesiocopiapite, phosphosiderite, pyrite, realgar and talmessite and formed from the oxidation of As-bearing primary phases and alteration by saline fluids derived from evaporating meteoric water under hyperarid conditions. Cuyaite occurs as pale brown thin needles (elongated on ), typically in divergent sprays and subparallel intergrowths. The streak is white. Crystals are transparent with adamantine lustre; subparallel intergrowths exhibit silky lustre. The mineral has Mohs hardness of 2½, is brittle, exhibits no cleavage and has irregular fracture. The calculated density is 4.140 g cm–3. Cuyaite is optically biaxial (–), with α = 1.87(1), β = 1.956(calc) and γ = 1.98(1), determined in white light; 2Vmeas = 60(1)°; and orientation: X = b and Y ^ a = 53° in obtuse β. Electron microprobe analyses provided the empirical formula Ca2.03Mn3+0.95(As3+13.66Sb3+0.65)Σ14.31O24Cl0.88. The six strongest powder X-ray diffraction lines are [dobs Å(I)(hkl)]: 4.73(45)(111,
14), 3.035(28)(213), 3.004(37)(204), 2.931(90)(
15, 312) and 2.779(28)(020). Cuyaite is monoclinic, Pn, a = 14.7231(6), b = 5.58709(19), c = 17.4185(12) Å, β = 112.451(8)°, V = 1324.23(14) Å3 and Z = 2. In the crystal structure of cuyaite (R1 = 0.0369 for 2095 I > 2σI reflections), AsO3 pyramids share O corners to form a ‘loose’ 3D framework; Jahn–Teller distorted Mn3+O6 octahedra and CaO8 polyhedra link by edges and corners to form columns; the columns also link by edge- and corner-sharing to the AsO3 pyramids in the framework; Cl occupies channels along  in the framework. The Raman spectrum is consistent with the presence of multiple As3+O3 groups.
Treatment resistant schizophrenia (TRS) is one of the most disabling of psychiatric disorders, affecting about 1/3 of patients. First-line treatments include both atypical and typical antipsychotics. The original atypical, clozapine, is a final option, and although it has been shown to be the only effective treatment for TRS, many patients do not respond well to clozapine. Clozapine use is related to adverse events, most notably agranulocytosis, a potentially fatal blood disorder which affects about 1% of those prescribed clozapine and requires regular blood monitoring. This as a barrier to prescription and there is a long delay in access for TRS patients, of five or more years, from first antipsychotic prescription. Better tools to predict treatment resistance and to identify risk of adverse events would allow faster and safer access to clozapine for patients who are likely to benefit from it. The CRESTAR project (www.crestar-project.eu) is a European Framework 7 collaborative project that aims to develop tools to predict i) treatment response, particularly patients who are less likely to respond to usual antipsychotics, indicating treatment with clozapine as early as possible, ii) patients who are at high or low risk of adverse events and side effects, iii) extreme TRS patients so that they can be stratified in clinical trials for novel treatments. CRESTAR has addressed these questions by examining genome-wide association data, genome sequence, epigenetic biomarkers and epidemiological data in European patient cohorts characterized for treatment response, and adverse drug reaction using data from clozapine therapeutic drug monitoring and linked National population medical and pharmacy databases, to identify predictive factors. In parallel CRESTAR will perform health economic research on potential benefits, and ethics and patient-centred research with stakeholders.
The provision of support for people with autism spectrum disorder (ASD) within the community is improving as a consequence of policy and legislative changes. However, specialist services are not currently provided in prisons.
This aim of the study was to determine the extent of ASD and co-occurring mental health problems among prisoners. We tested the hypothesis that ASD traits would be unrecognised by prison staff and would be significantly associated with increased rates of anxiety, depression and suicidality.
ASD traits were measured among 240 prisoners in a resettlement prison in London, UK using the 20-item Autism Quotient (AQ-20). Anxiety, depression and suicidality were assessed using the Mini International Neuropsychiatric Interview (MINI).
There were 39 participants (16%) with an AQ-20 score ≥10; indicating significant autistic traits. Mental health data were available for 37 ‘high autistic trait’ participants and another 101 prisoners with no/low ASD traits. There was a significant positive association between AQ-20 and suicidality scores (r=.29, p=0.001). Participants with ASD traits had significantly higher suicidality scores (means=15.1 vs. 5, p= 0.001) and chi-square analysis showed that they were more likely to have a high suicidality rating (27% vs. 8%, p=0.003) than those without ASD traits. Moreover, those with ASD were significantly more likely to be experiencing a current episode of depression (30% vs. 6%, p<0.001) or Generalised Anxiety Disorder (GAD) (27% vs. 11% p=0.019).
Our initial data suggests that severity of ASD traits is a risk factor for suicidality and common mental health problems among prisoners.
This chapter focuses on breaking down the process of using questions to gather information from others (i.e., inquiry) into its subcomponent parts to better understand the circumstances under which preschool-aged children can and will ask questions to gather information from others. We see the process of inquiry as involving at least four steps: determining when to engage in inquiry, deciding what to ask, selecting whom to question, and evaluating the information gathered to decide if inquiry should conclude or continue. In this chapter, we will briefly overview what we know about children’s ability to succeed at each of these steps during the preschool years, followed by a discussion of possible reasons for individual differences. The chapter concludes with implications for future research, including the importance of reflecting on the cost–benefit analysis children may undertake when determining whether or not to engage in each step of inquiry.
Acifluorfen is a nonsystemic PPO-inhibiting herbicide commonly used for POST Palmer amaranth control in soybean, peanut, and rice across the southern United States. Concerns have been raised regarding herbicide selection pressure and particle drift, increasing the need for application practices that optimize herbicide efficacy while mitigating spray drift. Field research was conducted in 2016, 2017, and 2018 in Mississippi and Nebraska to evaluate the influence of a range of spray droplet sizes [150 μm (Fine) to 900 μm (Ultra Coarse)], using acifluorfen to create a novel Palmer amaranth management recommendation using pulse width modulation (PWM) technology. A pooled site-year generalized additive model (GAM) analysis suggested that 150-μm (Fine) droplets should be used to obtain the greatest Palmer amaranth control and dry biomass reduction. Nevertheless, GAM models indicated that only 7.2% of the variability observed in Palmer amaranth control was due to differences in spray droplet size. Therefore, location-specific GAM analyses were performed to account for geographical differences to increase the accuracy of prediction models. GAM models suggested that 250-μm (Medium) droplets optimize acifluorfen efficacy on Palmer amaranth in Dundee, MS, and 310-μm (Medium) droplets could sustain 90% of maximum weed control. Specific models for Beaver City, NE, indicated that 150-μm (Fine) droplets provide maximum Palmer amaranth control, and 340-μm (Medium) droplets could maintain 90% of greatest weed control. For Robinsonville, MS, optimal Palmer amaranth control could be obtained with 370-μm (Coarse) droplets, and 90% maximum control could be sustained with 680 μm (Ultra Coarse) droplets. Differences in optimal droplet size across location could be a result of convoluted interactions between droplet size, weather conditions, population density, plant morphology, and soil fertility levels. Future research should adopt a holistic approach to identify and investigate the influence of environmental and application parameters to optimize droplet size recommendations.
− ESG–Agency scholars frequently use power as an explanatory variable, but often without definition or theoretical conceptualization. − Reflections on power in earth system governance research are divided between agency-centered (power to) and structure-centered (power over) perspectives, which mirrors the historic schism between liberal and critical International Relations scholars. − In the future, more comprehensive conceptualizations of power will strengthen the persuasiveness of normative arguments in ESG–Agency scholarship.
Herbicide applications performed with pulse width modulation (PWM) sprayers to deliver specific spray droplet sizes could maintain product efficacy, minimize potential off-target movement, and increase flexibility in field operations. Given the continuous expansion of herbicide-resistant Palmer amaranth populations across the southern and midwestern United States, efficacious and cost-effective means of application are needed to maximize Palmer amaranth control. Experiments were conducted in two locations in Mississippi (2016, 2017, and 2018) and one location in Nebraska (2016 and 2017) for a total of 7 site-years. The objective of this study was to evaluate the influence of a range of spray droplet sizes [150 (Fine) to 900 μm (Ultra Coarse)] on lactofen and acifluorfen efficacy for Palmer amaranth control. The results of this research indicated that spray droplet size did not influence lactofen efficacy on Palmer amaranth. Palmer amaranth control and percent dry-biomass reduction remained consistent with lactofen applied within the aforementioned droplet size range. Therefore, larger spray droplets should be used as part of a drift mitigation approach. In contrast, acifluorfen application with 300-μm (Medium) spray droplets provided the greatest Palmer amaranth control. Although percent biomass reduction was numerically greater with 300-μm (Medium) droplets, results did not differ with respect to spray droplet size, possibly as a result of initial plant injury, causing weight loss, followed by regrowth. Overall, 900-μm (Ultra Coarse) droplets could be used effectively without compromising lactofen efficacy on Palmer amaranth, and 300-μm (Medium) droplets should be used to achieve maximum Palmer amaranth control with acifluorfen.
This article surveys the emergence and usage of the redefinition of man not as animal rationale (rational animal) but as animal religiosum (religious animal) by numerous English theologians between 1650 and 1700. Across the continuum of English Protestant thought, human nature was being redescribed as unique due to its religious, not primarily its rational, capabilities. This article charts said appearance as a contribution to debates over man's relationship with God; then its subsequent incorporation into the discussion over the theological consequences of arguments in favor of animal rationality, as well as its uses in anti-atheist apologetics; and then the sudden disappearance of the definition of man as animal religiosum at the beginning of the eighteenth century. In doing so, the article hopes to make a useful contribution to our understanding of changing early modern understandings of human nature by reasserting the significance of theological writing in the dispute over the relationship between humans and beasts. As a consequence, it offers a more wide-ranging account of man as animal religiosum than the current focus on “Cambridge Platonism” and “Latitudinarianism” allows.
The mineral ‘oboyerite’, first described in 1979 from the Grand Central mine, Tombstone, Cochise County, Arizona, USA, has been re-examined. The type specimen from the Natural History Museum, London and a specimen from the Natural History Museum of Los Angeles County (traceable to S. A Williams, who first described ‘oboyerite’) were analysed in this study. The discreditation of ‘oboyerite’ as a valid mineral species has been approved by the Commission on New Minerals, Nomenclature and Classification of the International Mineralogical Association (Proposal 19-D). Single-crystal X-ray diffraction, powder X-ray diffraction, electron probe microanalysis and scanning electron microscopy were all employed to show that ‘oboyerite’ is formed of at least two distinct phases, including the lead–tellurium oxysalt minerals ottoite and plumbotellurite. During the course of the discreditation, plumbotellurite was confirmed to be identical to the synthetic compound α-Pb2+Te4+O3. Previously, in some mineralogical literature plumbotellurite was described as orthorhombic with no known crystal structure.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
A 2018 workshop on the White Mountain Apache Tribe lands in Arizona examined ways to enhance investigations into cultural property crime (CPC) through applications of rapidly evolving methods from archaeological science. CPC (also looting, graverobbing) refers to unauthorized damage, removal, or trafficking in materials possessing blends of communal, aesthetic, and scientific values. The Fort Apache workshop integrated four generally partitioned domains of CPC expertise: (1) theories of perpetrators’ motivations and methods; (2) recommended practice in sustaining public and community opposition to CPC; (3) tactics and strategies for documenting, investigating, and prosecuting CPC; and (4) forensic sedimentology—uses of biophysical sciences to link sediments from implicated persons and objects to crime scenes. Forensic sedimentology served as the touchstone for dialogues among experts in criminology, archaeological sciences, law enforcement, and heritage stewardship. Field visits to CPC crime scenes and workshop deliberations identified pathways toward integrating CPC theory and practice with forensic sedimentology’s potent battery of analytic methods.
The crystal structure of tlapallite has been determined using single-crystal X-ray diffraction and supported by electron probe micro-analysis, powder diffraction and Raman spectroscopy. Tlapallite is trigonal, space group P321, with a = 9.1219(17) Å, c = 11.9320(9) Å and V = 859.8(3) Å3, and was refined to R1 = 0.0296 for 786 reflections with I > 2σ(I). This study resulted from the discovery of well-crystallised tlapallite at the Wildcat prospect, Utah, USA. The chemical formula of tlapallite has been revised to (Ca,Pb)3CaCu6[Te4+3Te6+O12]2(Te4+O3)2(SO4)2·3H2O, or more simply (Ca,Pb)3CaCu6Te4+8Te6+2O30(SO4)2·3H2O, from H6(Ca,Pb)2(Cu,Zn)3(TeO3)4(TeO6)(SO4). The tlapallite structure consists of layers containing distorted Cu2+O6 octahedra, Te6+O6 octahedra and Te4+O4 disphenoids (which together form the new mixed-valence phyllotellurate anion [Te4+3Te6+O12]12−), Te4+O3 trigonal pyramids and CaO8 polyhedra. SO4 tetrahedra, Ca(H2O)3O6 polyhedra and H2O groups fill the space between the layers. Tlapallite is only the second naturally occurring compound containing tellurium in both the 4+ and 6+ oxidation states with a known crystal structure, the other being carlfriesite, CaTe4+2Te6+O8. Carlfriesite is the predominant secondary tellurium mineral at the Wildcat prospect. We also present an updated structure for carlfriesite, which has been refined to R1 = 0.0230 for 874 reflections with I > 2σ(I). This updated structural refinement improves upon the one reported previously by refining all atoms anisotropically and presenting models of bond valence and Te4+ secondary bonding.
Following stage 1 palliation, delayed sternal closure may be used as a technique to enhance thoracic compliance but may also prolong the length of stay and increase the risk of infection.
We reviewed all neonates undergoing stage 1 palliation at our institution between 2010 and 2017 to describe the effects of delayed sternal closure.
During the study period, 193 patients underwent stage 1 palliation, of whom 12 died before an attempt at sternal closure. Among the 25 patients who underwent primary sternal closure, 4 (16%) had sternal reopening within 24 hours. Among the 156 infants who underwent delayed sternal closure at 4 [3,6] days post-operatively, 11 (7.1%) had one or more failed attempts at sternal closure. Patients undergoing primary sternal closure had a shorter duration of mechanical ventilation and intensive care unit length of stay. Patients who failed delayed sternal closure had a longer aortic cross-clamp time (123±42 versus 99±35 minutes, p=0.029) and circulatory arrest time (39±28 versus 19±17 minutes, p=0.0009) than those who did not fail. Failure of delayed sternal closure was also closely associated with Technical Performance Score: 1.3% of patients with a score of 1 failed sternal closure compared with 18.9% of patients with a score of 3 (p=0.0028). Among the haemodynamic and ventilatory parameters studied, only superior caval vein saturation following sternal closure was different between patients who did and did not fail sternal closure (30±7 versus 42±10%, p=0.002). All patients who failed sternal closure did so within 24 hours owing to hypoxaemia, hypercarbia, or haemodynamic impairment.
When performed according to our current clinical practice, sternal closure causes transient and mild changes in haemodynamic and ventilatory parameters. Monitoring of SvO2 following sternal closure may permit early identification of patients at risk for failure.
The effect of transportation and lairage on the faecal shedding and post-slaughter contamination of carcasses with Escherichia coli O157 and O26 in young calves (4–7-day-old) was assessed in a cohort study at a regional calf-processing plant in the North Island of New Zealand, following 60 calves as cohorts from six dairy farms to slaughter. Multiple samples from each animal at pre-slaughter (recto-anal mucosal swab) and carcass at post-slaughter (sponge swab) were collected and screened using real-time PCR and culture isolation methods for the presence of E. coli O157 and O26 (Shiga toxin-producing E. coli (STEC) and non-STEC). Genotype analysis of E. coli O157 and O26 isolates provided little evidence of faecal–oral transmission of infection between calves during transportation and lairage. Increased cross-contamination of hides and carcasses with E. coli O157 and O26 between co-transported calves was confirmed at pre-hide removal and post-evisceration stages but not at pre-boning (at the end of dressing prior to chilling), indicating that good hygiene practices and application of an approved intervention effectively controlled carcass contamination. This study was the first of its kind to assess the impact of transportation and lairage on the faecal carriage and post-harvest contamination of carcasses with E. coli O157 and O26 in very young calves.
The Atypical Maternal Behavior Instrument for Assessment and Classification (AMBIANCE; Bronfman, Madigan, & Lyons-Ruth, 2009–2014; Bronfman, Parsons, & Lyons-Ruth, 1992–2004) is a widely used and well-validated measure for assessing disrupted forms of caregiver responsiveness within parent–child interactions. However, it requires evaluating approximately 150 behavioral items from videotape and extensive training to code, thus making its use impractical in most clinical contexts. Accordingly, the primary aim of the current study was to identify a reduced set of behavioral indicators most central to the AMBIANCE coding system using latent-trait item response theory (IRT) models. Observed mother–infant interaction data previously coded with the AMBIANCE was pooled from laboratories in both North America and Europe (N = 343). Using 2-parameter logistic IRT models, a reduced set of 45 AMBIANCE items was identified. Preliminary convergent and discriminant validity was evaluated in relation to classifications of maternal disrupted communication assigned using the full set of AMBIANCE indicators, to infant attachment disorganization, and to maternal sensitivity. The results supported the construct validity of the refined item set, opening the way for development of a brief screening measure for disrupted maternal communication. IRT models in clinical scale refinement and their potential for bridging clinical and research objectives in developmental psychopathology are discussed.
A comparative study is presented of the chemistry and crystallography of zinc-bearing strunzites from Hagendorf Süd, Bavaria, Germany and the Sitio do Castelo mine, Folgosinho, Portugal. Electron microprobe analyses of samples from the two localities show quite different cation substitutions. The Hagendorf Süd mineral is a Zn-bearing ferristrunzite, with compositional zoning due to Zn2+ replacing predominantly Fe3+ as well as minor Mn2+, whereas the Portugese mineral is a Zn-bearing strunzite, in which Zn2+ replaces Mn2+, with minor replacement of Fe3+ by Mn3+. Zincostrunzite, with dominant Zn in the interlayer octahedrally coordinated site, is a new strunzite-group mineral that has been characterized at both locations. Analysis of single-crystal synchrotron data for zinc-bearing ferristrunzite and zincostrunzite crystals from Hagendorf Süd show that the structures of both minerals contain zeolitic water in the interlayer region. The formula for strunzite-group minerals containing the zeolitic water is MFe23+(PO4)2(OH)2·6.5H2O, M=Fe, Mn, Zn. This formulation agrees with that found for zincostrunzite from the Sitio do Castelo mine, but differs from that reported previously for strunzite, MFe2+(PO4)2(OH)2·6H2O, which has no interlayer water. Interestingly, the zincostrunzites from the two localities differ in the location of the interlayer water molecule, with a corresponding difference in the H bonding.