Adolescents and Suicide: Restoring the Kin Network

Hogg Foundation for Mental Healt

The Relationship Development Assessment - Research Version: Preliminary validation of a clinical tool and coding schemes to measure parent-child interaction in autism.

The aim of this project was to replicate and extend findings from two recent studies on parent-child relatedness in autism (Beurkens, Hobson, & Hobson, 2013; Hobson, Tarver, Beurkens, & Hobson, 2013, under review) by adapting an observational assessment and coding schemes of parent-child relatedness for the clinical context and examining their validity and reliability. The coding schemes focussed on three aspects of relatedness: joint attentional focus (Adamson, Bakeman, & Deckner, 2004), the capacity to co-regulate an interaction and the capacity to share emotional experiences. The participants were 40 children (20 with autism, 20 without autism) aged 6-14, and their parents. Parent-child dyads took part in the observational assessment and were coded on these schemes. Comparisons were made with standardised measures of autism severity (Autism Diagnostic Observation Schedule, ADOS: Lord, Rutter, DiLavore, & Risi, 2001; Social Responsiveness Scale, SRS: Constantino & Gruber, 2005), relationship quality (Parent Child Relationship Inventory, PCRI: Gerard, 1994) and quality of parent-child interaction (Dyadic Coding Scales, DCS: Humber & Moss, 2005). Inter-rater reliability was very good and, as predicted, codes both diverged from the measure of parent-child relationship and converged with a separate measure of parent-child interaction quality. A detailed profile review revealed nuanced areas of group and individual differences which may be specific to verbally-able school-age children. The results support the utility of the Relationship Development Assessment - Research Version for clinical practice

MK-0448, a Specific Kv1.5 Inhibitor: Safety, Pharmacokinetics and Pharmacodynamic Electrophysiology in Experimental Animal Models and in Humans.

BACKGROUND: -We evaluated the viability of I(Kur) as a target for maintenance of sinus rhythm in patients with a history of atrial fibrillation through the testing of MK-0448, a novel I(Kur) inhibitor. METHODS AND RESULTS: -In vitro MK-0448 studies demonstrated strong inhibition of I(Kur) with minimal off-target activity. In vivo MK-0448 studies in normal anesthetized dogs demonstrated significant prolongation of the atrial refractory period compared with vehicle controls without affecting the ventricular refractory period. In studies of a conscious dog heart failure model, sustained AF was terminated with bolus intravenous MK-0448 doses of 0.03 and 0.1 mg/kg. These data led to a two-part first-in-human study: Part I evaluated safety and pharmacokinetics, and Part II was an invasive electrophysiologic (EP) study in healthy subjects. MK-0448 was well-tolerated with mild adverse experiences, most commonly irritation at the injection site. During the EP study, ascending doses of MK-0448 were administered, but no increases in atrial or ventricular refractoriness were detected despite achieving plasma concentrations in excess of 2 μM. Follow-up studies in normal anesthetized dogs designed to assess the influence of autonomic tone demonstrated that prolongation of atrial refractoriness with MK-0448 was markedly attenuated in the presence of vagal nerve simulation, suggesting that the effects of I(Kur) blockade on atrial repolarization may be negated by enhanced parasympathetic neural tone. CONCLUSIONS: -The contribution of I(Kur) to human atrial electrophysiology is less prominent than in preclinical models and therefore is likely to be of limited therapeutic value for the prevention of atrial fibrillation

Assessment of the relationship between stenosis severity and distribution of coronary artery stenoses on multislice computed tomographic angiography and myocardial ischemia detected by single photon emission computed tomography

The relationship between luminal stenosis measured by coronary CT angiography (CCTA) and severity of stress-induced ischemia seen on single photon emission computed tomographic myocardial perfusion imaging (SPECT-MPI) is not clearly defined. We sought to evaluate the relationship between stenosis severity assessed by CCTA and ischemia on SPECT-MPI. ECG-gated CCTA (64 slice dual source CT) and SPECT-MPI were performed within 6 months in 292 patients (ages 26-91, 73% male) with no prior history of coronary artery disease. Maximal coronary luminal narrowing, graded as 0, ≥25%, 50%, 70%, or 90% visual diameter reduction, was consensually assessed by two expert readers. Perfusion defect on SPECT-MPI was assessed by computer-assisted visual interpretation by an expert reader using the standard 17 segment, 5 point-scoring model (stress perfusion defect of ≥5% = abnormal). By SPECT-MPI, abnormal perfusion was seen in 46/292 patients. With increasing stenosis severity, positive predictive value (PPV) increased (42%, 51%, and 74%, P = .01) and negative predictive value was relatively unchanged (97%, 95%, and 91%) in detecting perfusion abnormalities on SPECT-MPI. In a receiver operator curve analysis, stenosis of 50% and 70% were equally effective in differentiating between the presence and absence of ischemia. In a multivariate analysis that included stenosis severity, multivessel disease, plaque composition, and presence of serial stenoses in a coronary artery, the strongest predictors of ischemia were stenosis of 50-89%, odds ratio (OR) 7.31, P = .001, stenosis ≥90%, OR 34.05, P = .0001, and serial stenosis ≥50% OR of 3.55, P = .006. The PPV of CCTA for ischemia by SPECT-MPI rises as stenosis severity increases. Luminal stenosis ≥90% on CCTA strongly predicts ischemia, while <50% stenosis strongly predicts the absence of ischemia. Serial stenosis of ≥50% in a vessel may offer incremental value in addition to stenosis severity in predicting ischemia

On the relevance of the mathematics curriculum to young people

In this paper we draw upon focus group data from a large study of learner trajectories through 14-19 mathematics education to think about the notion of relevance in the mathematics curriculum. Drawing on data from three socially distanced sites we explore how different emphases on what might be termed practical, process and/or professional forms of relevance affect the experiences and aspirations of learners of mathematics. We consider whether an emphasis on practical relevance in schools serving relatively disadvantaged communities might aid the reproduction of students’ social position. This leads us to suggest that a fourth category of curriculum relevance – political relevance – is largely missing from classrooms

Engaging with issues of emotionality in mathematics teacher education for social justice

This article focuses on the relationship between social justice, emotionality and mathematics teaching in the context of the education of prospective teachers of mathematics. A relational approach to social justice calls for giving attention to enacting socially-just relationships in mathematics classrooms. Emotionality and social justice in teaching mathematics variously intersect, interrelate or interweave. An intervention, usng creative action methods, with a cohort of prospective teachers addressing these issues is described to illustrate the connection between emotionality and social justice in the context of mathematics teacher education. Creative action methods involve a variety of dramatic, interactive and experiential tools that can promote personal and group engagement and embodied reflection. The intervention aimed to engage the prospective teachers with some key issues for social justice in mathematics education through dialogue about the emotionality of teaching and learning mathematics. Some of the possibilities and limits of using such methods are considered

Pre- and Posttranslational Regulation of Β-Endorphin Biosynthesis in the CNS: Effects of Chronic Naltrexone Treatment

There appear to be two anatomically distinct Β-endorphin (ΒE) pathways in the brain, the major one originating in the arcuate nucleus of the hypothalamus and a smaller one in the area of the nucleus tractus solitarius (NTS) of the caudal medulla. Previous studies have shown that these two proopiomelanocortin (POMC) systems may be differentially regulated by chronic morphine treatment, with arcuate cells down-regulated and NTS cells unaffected. In the present experiments, we examined the effects of chronic opiate antagonist treatment on ΒE biosynthesis across different CNS regions to assess whether the arcuate POMC system would be regulated in the opposite direction to that seen after opiate agonist treatment and to determine whether different ΒE-containing areas might be differentially regulated. Male adult rats were administered naltrexone (NTX) by various routes for 8 days (subcutaneous pellets, osmotic minipumps, or repeated intraperitoneal injections). Brain and spinal cord regions were assayed for total ΒE-ir, different molecular weight immunoreactive Β-endorphin (ΒE-ir) peptides, and POMC mRNA. Chronic NTX treatment, regardless of the route of administration, reduced total ΒE-ir concentrations by 30–40% in diencephalic areas (the arcuate nucleus, the remaining hypothalamus, and the thalamus) and the midbrain, but had no effect on ΒE-ir in the NTS or any region of the spinal cord. At the same time, NTX pelleting increased POMC mRNA levels in the arcuate to ∼ 140% of control values. These data suggest that arcuate POMC neurons are up-regulated after chronic NTX treatment (whereas NTS and spinal cord systems remain unaffected) and that they appear to be under tonic inhibition by endogenous opioids. Chromatographic analyses demonstrated that, after chronic NTX pelleting, the ratio of full length ΒE 1–31 to more processed ΒE-ir peptides (i.e., ΒE 1–27 and ΒE 1–26 ) tended to increase in a dose-dependent manner in diencephalic areas. Because ΒE 1–31 is the only POMC product that possesses opioid agonist properties, and ΒE 1–27 has been posited to function as an endogenous anatgonist of ΒE 1–31 , the NTX-induced changes in the relative concentrations of ΒE 1–31 and ΒE 1–27 /ΒE 1–26 may represent a novel regulatory mechanism of POMC cells to alter the opioid signal in the synapse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65603/1/j.1471-4159.1993.tb05820.x.pd

The owl spreads its wings: global and international education within the local from critical perspectives

Within an era of a New Knowledge Society, assumptions abound regarding the ‘goodness' and justice of global interconnections and distributions of knowledge through international educational organizations and structures worldwide. Just as George Bush Jr. in attempting to justify the invasion of Iraq made claim to the democratic goodness of the US ‘spreading their freedoms' in the interests of an all-encompassing democratization of the world, so the assumption that sharing educational knowledge, especially an ‘all-knowing North' with a ‘helpless South' is without question for the greater good of all humanity

Cornucopia: Temporal safety for CHERI heaps

Use-after-free violations of temporal memory safety continue to plague software systems, underpinning many high-impact exploits. The CHERI capability system shows great promise in achieving C and C++ language spatial memory safety, preventing out-of-bounds accesses. Enforcing language-level temporal safety on CHERI requires capability revocation, traditionally achieved either via table lookups (avoided for performance in the CHERI design) or by identifying capabilities in memory to revoke them (similar to a garbage-collector sweep). CHERIvoke, a prior feasibility study, suggested that CHERI’s tagged capabilities could make this latter strategy viable, but modeled only architectural limits and did not consider the full implementation or evaluation of the approach. Cornucopia is a lightweight capability revocation system for CHERI that implements non-probabilistic C/C++ temporal memory safety for standard heap allocations. It extends the CheriBSD virtual-memory subsystem to track capability flow through memory and provides a concurrent kernel-resident revocation service that is amenable to multi-processor and hardware acceleration. We demonstrate an average overhead of less than 2% and a worst-case of 8.9% for concurrent revocation on compatible SPEC CPU2006 benchmarks on a multi-core CHERI CPU on FPGA, and we validate Cornucopia against the Juliet test suite’s corpus of temporally unsafe programs. We test its compatibility with a large corpus of C programs by using a revoking allocator as the system allocator while booting multi-user CheriBSD. Cornucopia is a viable strategy for always-on temporal heap memory safety, suitable for production environments.This work was supported by the Defense Advanced Research Projects Agency (DARPA) and the Air Force Research Laboratory (AFRL), under contracts FA8750-10-C-0237 (“CTSRD”) and HR0011-18-C-0016 (“ECATS”). We also acknowledge the EPSRC REMS Programme Grant (EP/K008528/1), the ABP Grant (EP/P020011/1), the ERC ELVER Advanced Grant (789108), the Gates Cambridge Trust, Arm Limited, HP Enterprise, and Google, Inc

Preliminary Study of Prospective ECG-Gated 320-Detector CT Coronary Angiography in Patients with Ventricular Premature Beats

BACKGROUND: To study the applicability of prospective ECG-gated 320-detector CT coronary angiography (CTCA) in patients with ventricular premature beats (VPB), and determine the scanning mode that best maximizes image quality and reduces radiation dose. METHODS: 110 patients were divided into a VPB group (60 cases) and a control group (50 cases) using CTCA. All the patients then underwent coronary angiography (CAG) within one month. CAG served as a reference standard through which the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CTCA in diagnosing significant coronary artery stenosis (luminal stenosis ≥50%) could be analyzed. The two radiologists with more than 3 years' experience in cardiac CT each finished the image analysis after consultation. A personalized scanning mode was adopted to compare image quality and radiation dose between the two groups. METHODOLOGY/PRINCIPAL FINDINGS: At the coronary artery segment level, sensitivity, specificity, PPV, and NPV in the premature beat group were 92.55%, 98.21%, 88.51%, and 98.72% respectively. In the control group these values were found to be 95.79%, 98.42%, 90.11%, and 99.28% respectively. Between the two groups, specificity, sensitivity PPV, NPV was no significant difference. The two groups had no significant difference in image quality score (P>0.05). Heart rate (77.20±12.07 bpm) and radiation dose (14.62±1.37 mSv) in the premature beat group were higher than heart rate (58.72±4.73 bpm) and radiation dose (3.08±2.35 mSv) in the control group. In theVPB group, the radiation dose (34.55±7.12 mSv) for S-field scanning was significantly higher than the radiation dose (15.10±1.12 mSv) for M-field scanning. CONCLUSIONS/SIGNIFICANCE: With prospective ECG-gated scanning for VPB, the diagnostic accuracy of coronary artery stenosis is very high. Scanning field adjustment can reduce radiation dose while maintaining good image quality. For patients with slow heart rates and good rhythm, there was no statistically significant difference in image quality