Exploring different theoretical frontiers – A symposium

Providing for a praxis of uncertainty, theoretical traditions that undercover how knowledge, power, and identity are interwoven and constituted in and through socio-cultural and -political discourses characterize the sociopolitical-turn moment in mathematics education research. Researchers who work in the sociopolitical-turn moment pull from a variety of theoretical perspectives most often located in the emancipate and/or deconstruct paradigms of inquiry. In this symposium, panelists discuss how different theoretical traditions available to researchers in the sociopolitical-turn moment provide new productive ways to think and rethink mathematics teaching and learning

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

Thunderclap: Exploring Vulnerabilities in Operating System IOMMU Protection via DMA from Untrustworthy Peripherals

Direct Memory Access (DMA) attacks have been known for many years: DMA-enabled I/O peripherals have complete access to the state of a computer and can fully compromise it including reading and writing all of system memory. With the popularity of Thunderbolt 3 over USB Type-C and smart internal devices, opportunities for these attacks to be performed casually with only seconds of physical access to a computer have greatly broadened. In response, commodity hardware and operating-system (OS) vendors have incorporated support for Input-Output Memory Management Units (IOMMUs), which impose memory protection on DMA, and are widely believed to protect against DMA attacks. We investigate the state-of-the-art in IOMMU protection across OSes using a novel I/O security research platform, and find that current protections fall short when faced with a functional network peripheral that uses its complex interactions with the OS for ill intent, and demonstrate compromises against macOS, FreeBSD, and Linux, which notionally utilize IOMMUs to protect against DMA attackers. Windows only uses the IOMMU in limited cases and remains vulnerable. Using Thunderclap, an open-source FPGA research platform we built, we explore a number of novel exploit techniques to expose new classes of OS vulnerability. The complex vulnerability space for IOMMU-exposed shared memory available to DMA-enabled peripherals allows attackers to extract private data (sniffing cleartext VPN traffic) and hijack kernel control flow (launching a root shell) in seconds using devices such as USB-C projectors or power adapters. We have worked closely with OS vendors to remedy these vulnerability classes, and they have now shipped substantial feature improvements and mitigations as a result of our work.DARPA I2O FA8750-10-C-0237 ("CTSRD") DARPA MTO HR0011- 18-C-0016 ("ECATS") Arm Ltd Google Inc This work was also supported by EPSRC EP/R012458/1 (“IOSEC”)

Activated Met Signalling in the Developing Mouse Heart Leads to Cardiac Disease

BACKGROUND: The Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine involved in many physiological processes, including skeletal muscle, placenta and liver development. Little is known about its role and that of Met tyrosine kinase receptor in cardiac development. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we generated two transgenic mice with cardiac-specific, tetracycline-suppressible expression of either Hepatocyte Growth Factor (HGF) or the constitutively activated Tpr-Met kinase to explore: i) the effect of stimulation of the endogenous Met receptor by autocrine production of HGF and ii) the consequence of sustained activation of Met signalling in the heart. We first showed that Met is present in the neonatal cardiomyocytes and is responsive to exogenous HGF. Exogenous HGF starting from prenatal stage enhanced cardiac proliferation and reduced sarcomeric proteins and Connexin43 (Cx43) in newborn mice. As adults, these transgenics developed systolic contractile dysfunction. Conversely, prenatal Tpr-Met expression was lethal after birth. Inducing Tpr-Met expression during postnatal life caused early-onset heart failure, characterized by decreased Cx43, upregulation of fetal genes and hypertrophy. CONCLUSIONS/SIGNIFICANCE: Taken together, our data show that excessive activation of the HGF/Met system in development may result in cardiac damage and suggest that Met signalling may be implicated in the pathogenesis of cardiac disease

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

Intensive intervention for children and adolescents with autism in a community setting in Italy: a single-group longitudinal study

<p>Abstract</p> <p>Background</p> <p>Previous studies have shown favourable results with intensive behavioural treatment for children with autism: evidence has emerged that treatment can be successfully implemented in a community setting and in adolescent participants. The aim of this study was to describe the 2-year adaptive functioning outcome of children and adolescents with autism treated intensively within the context of special autism centres, as well as to evaluate family satisfaction with the activity of the centres.</p> <p>Methods</p> <p>Sixty participants with autism (20 females and 40 males, aged between 4 and 18 years) attending the semi-residential rehabilitation centres for autism located in the Abruzzo region (Central Italy) were followed up and their adaptive functioning was evaluated both at baseline and after one and two years using the Vineland Adaptive Behaviour Scales (VABS). Parents' satisfaction with the service was evaluated using the Orbetello Satisfaction Scale for Children and Adolescent Mental Health.</p> <p>Results</p> <p>The increase in VABS scores was significant on several domains in the different gender and age categories. It is worth noting that male children had improved a great deal (roughly, an effect size >0.20) in the domains of communication, daily living and motor skills (effect sizes 0.34, 0.45 and 0.27 respectively) whereas in male adolescents, a notable increase in VABS scores was recorded in the domain of socialization only (effect size 0.23). On the other hand, adaptive behaviour in female children increased in the domains of socialization and motor skills (effect sizes 0.27 and 0.42 respectively) whereas in female adolescents, good results were achieved in the domains of daily living, socialization and motor skills (effect sizes 0.22, 0.26 and 0.20 respectively).</p> <p>The level of satisfaction of users of the service over time was found to be substantial, even when they had recently started the program.</p> <p>Conclusions</p> <p>Our results support the implementation of special autism treatment community centres, based on a parent co-directed rehabilitative, intensive and early intervention. Further experimental research designed to document the effectiveness of services provided to children and adolescents with autism in the community is recommended.</p

The potency of the fs260 connexin43 mutant to impair keratinocyte differentiation is distinct from other disease-linked connexin43 mutants

Although there are currently 62 mutants of Cx43 (connexin43) that can cause ODDD (oculodentodigital dysplasia), only two mutants have also been reported to cause palmar plantar hyperkeratosis. To determine how mutants of Cx43 can lead to this skin disease, REKs (rat epidermal keratinocytes) were engineered to express an ODDD-associated Cx43 mutant always linked to skin disease (fs260), an ODDD-linked Cx43 mutant which has been reported to sometimes cause skin disease (fs230), Cx43 mutants which cause ODDD only (G21R, G138R), a mouse Cx43 mutant linked to ODDD (G60S), a non-disease-linked truncated Cx43 mutant that is trapped in the endoplasmic reticulum (Δ244*) or full-length Cx43. When grown in organotypic cultures, of all the mutants investigated, only the fs260-expressing REKs consistently developed a thinner stratum corneum and expressed lower levels of Cx43, Cx26 and loricrin in comparison with REKs overexpressing wild-type Cx43. REKs expressing the fs260 mutant also developed a larger organotypic vital layer after acetone-induced injury and exhibited characteristics of parakeratosis. Collectively, our results suggest that the increased skin disease burden exhibited in ODDD patients harbouring the fs260 mutant is probably due to multiple additive effects cause by the mutant during epidermal differentiation

Differential Pharmacological Actions of Methadone and Buprenorphine in Human Embryonic Kidney 293 Cells Coexpressing Human μ-Opioid and Opioid Receptor-Like 1 Receptors

Methadone and buprenorphine are used in maintenance therapy for heroin addicts. In this study, we compared their effects on adenylate cyclase (AC) activity in human embryonic kidney (HEK) 293 cells stably overexpressing human μ-opioid receptor (MOR) and nociceptin/opioid receptor-like 1 receptor (ORL1) simultaneously. After acute exposure, methadone inhibited AC activity; however, buprenorphine induced compromised AC inhibition. When naloxone was introduced after 30 min incubation with methadone, the AC activity was enhanced. This was not observed in the case of buprenorphine. Enhancement of the AC activity was more significant when the incubation lasted for 4 h, and prolonged exposure to buprenorphine elevated the AC activity as well. The removal of methadone and buprenorphine by washing also obtained similar AC superactivation as that revealed by naloxone challenge. The study demonstrated that methadone and buprenorphine exert initially different yet eventually convergent adaptive changes of AC activity in cells coexpressing human MOR and ORL1 receptors

The desmosome and pemphigus

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required