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Robin Mansell
Long Read: The Blind Spots in Digital Policy and Practice
As governments take steps towards regulating digital platforms, LSE's Professor Robin Mansell argues for more attention to the implementation of policies, and that we need to expose myths that hamper critical reflections on digital technologies and any harms they generate. This is a modified version of a Public Lecture in honour of receipt of an Honorary Doctorate from the Faculty of Economic and Social Sciences and Management, University of Fribourg, Switzerland, 16 November 2021.
Governments would like citizens to believe that achieving 'superpower' status in Artificial Intelligence (AI) innovation is the best way to assure our collective future. AI applications are expected to solve health pandemics, the global climate crisis, the spread of viral misinformation and a host of online harms. It is claimed that AI's algorithms are (or will be) trustworthy. The vision of our digital future is one where 'data is now less the trail that we leave behind us as we go through our lives, and more the medium through which we are living our lives' as the UK Information Commissioner's Office put it. Facebook's vision of a technology-enabled virtual 'multiverse' is said to be inclusive, creative, empowering and trusted. Government oversight of technology companies is expected to produce transparency, controlling for harmful outcomes. The European Union's Artificial Intelligence Regulation proposal says that AI should be a 'force for good in society'. It also says that uses of AI must be balanced so as not to restrict trade unnecessary. If regulatory 'guardrails' are not yet in place, they soon will be and corporate interests in profit will be balanced with public values of fairness, equity and democracy.
There is no absence of a more critical narrative. This narrative responds to the fact that countries are seeking first mover advantage in exploiting digital technologies. There are multiple concerns about 'deep tech' and 'smart data' which 'capitalise on data'. This is becoming the order of the day in the search for efficient optimised decision outcomes. Large digital tech companies – the GAFAM and data analytics companies such as Palantir Technologies in the US or Itransition in Belarus ‑ have lucrative contracts with military and public sector organisations and private firms. Critical assessments of AI innovation and the behaviours of these companies are linked to the observation that their primary aim is to make online 'clusters of transactions and relationships stickier' via a system of 'protocol-based control' as law professor Julie Cohen says. Their strategy is 'hypernudge'. The risks and harms for children and adults are occurring because of failures in the digital governance of capitalist markets in an era of data colonialism or surveillance capitalism.
A Crescendo of Digital Policy Measures
A crescendo of digital and AI harm mitigation measures is being put in place in the West, the global South and the East, to govern AI and digital platforms. In the Western democracies, it is being acknowledged by governments and by civil society actors that requiring people to live their lives while being tracked continuously is undermining human dignity. Four components of such measures are very prominent. One component is efforts to achieve a level market playing field to tackle what is variously called the 'significant and durable market power', 'substantial market power', 'strategic market status', 'bottleneck power' or the 'gatekeeper power' of the largest digital technology companies. In the US, the aim is to stimulate 'free and fair' competition through antitrust measures with some attention to privacy law. In the UK and Europe, the aim is to restrain the behaviour of these companies. Measures include data portability and interoperability and codes of conduct. However, each region or nation is striving – at the same time – for AI and digital technology market leadership. When the policy focus is on domestic or regional market competition, this is often confronted with scaremongering headlines such as 'Splitting up Facebook and Google would be great for China'. Toughening up approaches using competition policy may make markets more contestable, but they should not create unnecessary restrictions to trade because the competitive playing field is global.
A second set of measures is platform content moderation. The aim here is to achieve fairness, transparency and accountability of digital platforms' moderation of illegal (and, in the UK, harmful but not illegal) content. But, at the same time, the aim is to maintain favourable conditions for digital and AI innovation. A third component is data and privacy protection. The EU's General Data Protection Regulation or GDPR has been a pace setter for legislation in multiple jurisdictions, but does it not apply to anonymous and pseudo-anonymised data. This legislation has been accompanied by mounting calls for open data sharing in the UK and the EU to boost innovation and competitiveness. Last, but not the least, is ethics and ethical principles. 'High risk' AI systems will require testing in the EU before an AI system is put on the market and the UK is similarly promoting ethical AI innovation. Yet information about algorithms and complex machine learning systems requires tools and methods that are still in development: 'for policymakers and practitioners, it may be disappointing to see that many of these approaches are not 'ready to roll out'' as the Ada Lovelace Institute put it. Furthermore, political geography professor Louise Amoore insists that a high level of algorithmic transparency is not feasible to achieve. Meanwhile, while some companies are trying to demonstrate their ethical credentials, governments are concerned that ethical principles should not stand in the way of innovation.
Five Myths about Digital Policy and Regulatory Practice
Will moves to govern digital technology companies with the aim of protecting the public interest succeed in limiting digital companies' power and the harms associated with their digital systems? Digital governance requires principles and legislation, but it also requires implementation. Discussion about policy measures and regulation often neglects consideration of implementation practices associated with whatever digital governance regime is put in place – how implementation gives rise to outcomes, both expected and unexpected. This is a huge blind spot in the digital policy sphere. To understand the workings of policy and regulatory implementation, it is crucial to examine some of the myths that lead to a neglect of critical reflection on the implementation of policy and regulation.
Myth 1: individuals make well-informed rational choices about their online lives on a level market playing field
One myth is that individuals make well-informed rational choices about their online lives on a level market playing field. Each individual is assumed to be able to acquire information about the activity of all others and to adjust their behaviour accordingly. This myth pops up when it is argued that consumers need to be given a 'real choice' in the online world. It persists despite evidence that people do not read or comprehend privacy statements. An emphasis on individual 'real' choice typically leads to calls for investment in digital literacy and improved critical thinking. But as my LSE colleague Sonia Livingstone says, although it is crucial to improve digital literacy, 'we cannot teach what is unlearnable'. The myth of the level market playing field sustains claims that economic values will be balanced with citizen's fundamental rights because companies will compete by differentiating themselves in ways that are favourable to citizens. This myth biases policy and regulatory practice towards assuming there is an imagined child or adult who is motivated to – and has or will have the opportunity to – make informed choices about their mediated environment. It biases policy makers to imagine that contestable digital markets will foster the public good. Even those seeking to protect citizens' rights often succumb to this myth. For example, the UK-based 5Rights Foundation says that 'in a more competitive market, services would compete to offer better alternatives to users who prefer not to share their data, to reduce exposure to distressing material, to respond to user reports more quickly and better uphold community standards'. Yet competition can also encourage a 'race to the bottom'. The myth about rational choice and level competitive markets conceals that fact that the fully competitive market is an illusion.
Myth 2: Digital systems will allow individuals to control their online experiences in ways that are beneficial to them
A second myth is about technological fix responses to digital harms. Here the myth is that, in time, automated content moderation and algorithmic decision making will greatly reduce reliance on humans and that the costs to achieve transparency and greater individual control will decline. This myth suggests that digital systems will allow individuals to control their online experiences in ways that are beneficial to them. For example, design solutions will put users in control with 'a real choice' thanks to a variety of toolkits which let people decide what content they see and what data they release. The MyData initiative promises to yield 'market symmetry' between digital platforms and individual users. Tim Berners-Lee sees the use of 'pods' – personal online data stores – as enhancing individual control over data. These possibilities conceal the reality that people are still subject to private sector co-optation in an unlevel marketplace. Nevertheless, 'trust', 'safety' or 'privacy' by design are imagined to balance rights to privacy and freedom of expression with commercial ambitions. This myth supports claims that regulations will incentivise companies to design fairness and equity into their AI and digital systems. Yet, as these systems advance, even the designers understand less and less about what transpires between an algorithm's data inputs and its outputs. Regulatory practice is biased away from understanding that the commercial datafication model itself is the problem.
Myth 3: There will be minimal ambiguity in the interpretation of evidence concerning company practices
A third myth is about unambiguous evidence and transparency and it is connected to policy makers' claims about the capacity of legislative measures to yield regulatory certainty. It typically is suggested that there will be minimal ambiguity in the interpretation of evidence concerning company practices. Yet, for example, regarding digital harms, in evidence before the UK's House of Lords, the Minister for Digital and the Creative Industries said that its Online Safety Bill definition of psychological harm has no clinical basis. The UK government's own impact assessment of the Bill concludes that 'in some cases, it was not possible to establish a causal link between online activity and the harm'. Nevertheless, the myth is that there will be relatively little dispute about what digital operations give rise to a foreseeable risk of harm. This myth creates a bias towards assuming that research evidence will provide relatively clear guidance about what regulatory actions are needed even in the face of conflicting regulatory objectives. Regulation also depends on evidence to be available if transparency is to be achieved. Penalties levied on companies for failing to comply with information requests are assumed to be able to elicit reliable information for independent audit. The myth is that companies will be responsive to requests and that regulators (and the courts) will have a solid and relatively uncontested evidentiary basis for their decisions. Not only does this myth help to distract attention away from the fact that both quantitative and qualitative evidence are probabilistic, it also conceals the interpretative – often politicised – frameworks that policy makers and regulators bring to evidence once it is produced. It encourages the claim that the implementation of regulation will lead to certainty (and fairness) for all parties, and especially for businesses.
Myth 4: In democracies, regulatory agencies act independently of the state and companies
Myth four is about regulatory independence. In democracies, rules, procedures and safeguards are said to enable regulatory agencies to act independently of the state and companies. This myth about independence varies in detail depending on the country or region, but there are signs of erosion. For example, in the UK, the Online Safety Bill gives the Secretary of State the power to give direction to the regulator to 'reflect government policy' or for 'reasons of national security or public safety'. In practice, 'independent' regulatory institutions are dependent on the state and on companies in multiple ways. In some jurisdictions, legislation is opening the door for the state to define what is illegal (or harmful) speech. In the Western democracies, there are signs of declining, or even abandoned, procedural standards and interference by political actors in regulatory proceedings. Yet, the myth of independence persists, operating to encourage citizens to trust their political representatives to give primacy to their interests or, at least, to balance their interests with those of corporate actors through regulatory practice.
Myth 5: Once legislation is passed, it will be enforced effectively
A fifth myth is that once legislation is passed, it will be enforced effectively – capacity and skills will be upscaled to meet requirements. As an example of the need to unpack this myth, the EC's report on GDPR implementation notes that implementation is still fragmented across the member states. Budgets for data protection increased by 49% from 2016 to 2019 and staffing for data authorities grew by 42%, yet case loads continue to grow. The governments in Ireland and Luxembourg, where many tech companies are headquartered, lack the required resources to handle their cases. Meanwhile, the UK's Information Commissioner's Office found (in 2019) that the advertising industry was processing GDPR special category data without explicit consent and therefore unlawfully. Across Europe, the largest fines have been levied for security incidents with many fewer fines for privacy violations according to the EU's data. The myth of effective regulatory enforcement also persists in lower income countries which are being unevenly integrated into a datafied world. The World Bank's Data for Better Lives report acknowledges, for example, that for many lower income countries an integrated data governance system is an 'aspirational vision'. Nevertheless, discussion about digital governance in many of these countries includes repeated assertions that legislation will protect citizens from digital harms and be implemented in the public interest.
The myth about effective enforcement is robustly defended notwithstanding the fact that companies, themselves, cannot control certain online behaviours, sometimes even resorting to wholesale Internet shutdowns. They are practicing 'deplatformisation' when leading platforms shift right wing actors to the edges of the ecosystem, denying them access to their app stores or ejecting them from their cloud services. These actions are in the hands of companies, rarely regulators; and this gives rise to questions about freedom of expression and censorship. Trust marks, security devices and new codes of conduct to curtail disinformation and to protect data are being introduced and the development of the Internet of Things is seeing a lot of activity in this area. But enforcement, and the inadequacy of resources needed to achieve it, call into question assertions that legislative measures provide certainty for business and civil society stakeholder. High profile cases of illegal or harmful business behaviour are being pursued through anti-trust actions and other legislative routes and they receive much media coverage. There are instances of wins in competition policy enforcement as in the EU's case against Google's use of its own price comparison service to win unfair advantage over its European rivals. There are signs of more vigorous policy enforcement under the Biden Administration in the US against the largest digital platform companies. However, few of these developments directly tackle the fundamental underlying problem of an AI and digital platform industry that is guided, ultimately, by profit making incentives, not by public interests and values.
Why do Myths Matter?
Inquiries into blind spots in policy and practice have a long tradition in communications research. Communications professor Dallas Smythe, for example, argued in 1977 that the best way to address such blind spots is to examine the principal contradictions of capitalism. He insisted that the question that needs to be asked is about the economic function that providers of communication services serve in reproducing capitalist relations. In the case of AI and digital platforms, what functions are companies and their regulators performing in the interests of capital? What norms, beliefs and practices are shaping the implementation of regulation when it is translated from formal legislative and regulatory discourse into practice? Blind spots are maintained by myths and regression into myth is very common during periods of crisis such as the proliferation of illegal content and misinformation or biased algorithmic outcomes and ever more intrusive surveillance. Myths confer an illusory sense of mastery – for example, that we can control digital innovation in the public interest even in the face of mass exploitation of citizens' data for commercial purposes. Myths naturalise so that the basic digital and AI business models which rely on individuals' data are not fundamentally challenged.
The five myths considered here – rational choice and level competitive market playing fields, technological fixes, unambiguous evidence and transparency, regulatory independence, and effective enforcement – matter because they feed the blind spot in digital policy and regulation implementation. They sustain the argument that commercial datafication and AI applications can be operated 'for the public good' in the capitalist marketplace, subject to oversight. These myths bias regulatory practice towards favouring risk metrics and away from exposing the principal contradictions in digital and AI markets. They favour a belief that there is no alternative to the expansion of AI and commercial datafication. This is not to suggest that no change will happen as a result of legislation and regulatory action. It will happen and some of it potentially for 'good'. But the myths underpin unrealistic expectations that regulatory implementation will be able to favour citizens' interests. The blind spot about implementation ensures that the assumption that market equilibrium will eventually deliver optimal outcomes for all predominates. It sustains an all too familiar technology push agenda which flourishes as a 'social disease' as cultural studies professor Toby Miller calls it. It supports the EC's claim, that 'tracking and profiling of end users online is … not necessarily an issue' – if it is done in a controlled and transparent way. In practice, 'control' and 'transparency' are mythologised constructs that need to be subject to much more scrutiny than is evident in today's policy debates about AI and digital platform regulation.
Towards a Myth-busting agenda
It is being suggested that we need a new imaginary of our digital future; an imaginary of how technology can support, rather than undermine, democracy. For example, the UK House of Commons says, 'we need to create a vision of how technology can support rather than undermine representative parliamentary democracy'. An article in the New Yorker asks 'does tech need a new narrative?' But more than a new imaginary or a new narrative is needed. The myths sustaining the notion that citizen's interests are being protected because protective legislation has been (or is being) put in place need to be exposed. Without effective critique of the myths, new imaginaries will rest on practices guided by unrealistic assumptions about markets, individual rationality, decision making certainty, and effective regulatory implementation. Harvard Business School professor Shoshana Zuboff says 'it's not that we've failed to rein in Facebook and Google. We've not even tried'. And communication professor Mike Ananny says 'they are ours to control — if we can figure out how to do it'. Figuring out how to do it by passing legislation is one thing. But attending to how new policies and regulations are being implemented in practice is crucial. This receives much less attention and is the subject of much less research than is the race to put digital legislation and regulations in place.
Disputes about the risks and harms of technology innovation in the media and communications field are not new. Warnings about race and gender discrimination and anti-democratic norms linked to information collection and processing, for instance, have been common since the 1960s. The 1968 Council of Europe recommendation on Human Rights and Modern Scientific and Technological Developments, for instance, warned against 'newly developed techniques such as phone-tapping and eavesdropping to obtain private information, and against subliminal advertising and propaganda'. Steps were taken. If they had not been taken, citizens in Western democracies might not have the limited protections they have today. The view that it is acceptable to grant power to companies to use data as a basis for decisions that affect us all, so long as the state puts mitigating legislation in place, nonetheless, is very prominent today.
Resistance to the industry (and state) visions and business models for AI and datafication is possible, but only if myths such those outlined here can be dispelled. For researchers and policy makers, this means looking beyond the myths to critically examine promises about regulatory outcomes and the resources allocated to regulatory practice. It means examining the preferred knowledge claims that inform regulatory practice. It also means tracking instances of political interference in regulatory processes and monitoring gaps between promised regulatory outcomes and what companies do over time including their lobbying stances and their self-regulatory measures.
Well-funded research to unpack these and other myths is essential if alternative citizen rights-respecting digital futures are to have a chance of flourishing. Such evidence can help to make the case for alternatives to the dominant business models of AI innovation and commercial datafication. The space for alternatives, such as public service media platforms, non-use of tracking devices, collective institutions to finance online platforms, and governance arrangements – beyond state and market – for the public good, is constrained by the persistent promise that the private sector will deliver public benefit when it is overseen by effective regulation. But flourishing alternatives to market-driven digital and AI offerings will be a long time in coming without evidence-based myth-busting – 'technological somnambulism' will be our future.
New designs, ethical principles and codes of practice will be formulated and legislated across multiple jurisdictions. But if the myths go unchallenged, regulation of AI and digital platforms will be persistently blind to the origins of harms to citizens and to the erosion of public values. As Chris Freeman, a leading science, technology and innovation scholar said in the 1970s, if we substitute mathematics – in today's language, data analytics – for human understanding, society will be at risk of a 'reduction in social solidarity'. Social solidarity and democracy hang in the balance. They depend on whether greater attention can be given to the policy implementation blind spot.
This article gives the views of the author and does not represent the position of the Media@LSE blog, nor of the London School of Economics and Political Science.
Robin Mansell is Professor of New Media and the Internet in the Department of Media and Communications at LSE. She has training in several social science disciplines including psychology, social psychology, politics and economics and is a strong advocate of interdisciplinary research when it builds on the strengths of disciplinary inquiry. Her current research focuses on the political economy of 'platformisation' and 'datafication' and its social consequences for society and on the challenges of designing and implementing regulatory norms, rules and processes through institutions in diverse contexts around the world.
Posted In: Internet Governance
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Current and emerging brain applications of MR-guided focused ultrasound
Ying Meng ORCID: orcid.org/0000-0003-3180-24041,
Suganth Suppiah1,
Karim Mithani2,
Benjamin Solomon2,
Michael L. Schwartz1 &
Nir Lipsman1,2
Journal of Therapeutic Ultrasound volume 5, Article number: 26 (2017) Cite this article
MRI guided focused ultrasound is an emerging technique that uses acoustic energy to noninvasively treat intracranial disorders. At high frequencies, it can be used to raise tissue temperatures and ablate discrete brain targets with sub-millimeter accuracy. This application is currently under investigation for a broad range of clinical applications, including brain tumors, movement disorders, and psychiatric conditions. At low frequencies MRI guided focused ultrasound can be used to modulate neuronal activity and in conjunction with injected microbubbles, can open the blood-brain barrier to enhance the delivery of therapeutic compounds. The last decade has seen dramatic advances in the science of MRI guided focused ultrasound, helping elucidate both its mechanisms and potential in pre-clinical models, and its translational promise across myriad clinical applications. This review provides an update of current and emerging MRI guided focused ultrasound applications for intracranial disorders and describes future directions and challenges for the field.
The ability to focus acoustic energy through the intact skull on discrete brain targets has been a goal of ultrasound research for decades. Early efforts at therapeutic ultrasound in the brain, pioneered by the Fry brothers in the early 1950's, though successful, required removal of the overlying skull due to the bone's absorption and reflection of a large portion of ultrasound energy [1]. In the late 1990s, completely noninvasive treatment was realized with the development of a helmet device lined with multiple independent transducers, and the coupling of FUS to real-time magnetic resonance (MR) image guidance [2]. The MR guided FUS (MRgFUS) design allowed computer calculated and controlled steering of each element to achieve accurate targeting. The device is further coupled with thermography to allow real-time feedback on the effect of sonications. In one commercially available design, a spherical helmet device harnesses acoustic energy from over 1000 individual transducer elements operating between 650 and 720 kHz. Currently, the patient's head must be stabilized in a stereotactic frame and their hair must be shaved to allow good coupling between the transducers and scalp. Other devices may use fewer transducers, as well as the possibility to implant the system in the skull for ongoing ultrasound application [3].
Over the last decade the potential applications of MRgFUS in neurosurgery have significantly expanded. MRgFUS was recently approved by the US Food and Drug Administration (FDA) to perform thalamotomy for patients with medically refractory essential tremor (ET), and is currently under investigation for treatment of brain tumors, as well as treatment resistant psychiatric conditions (Fig. 1) [4]. Moreover, a recent cost-effective analysis suggested that MRgFUS may be cost-effective compared to other neuromodulation modalities, such as deep brain stimulation or stereotactic radiosurgery for the treatment of ET [5]. Currently, there are more than 25 focused ultrasound clinical trials publically registered for patients with neurological disorders ranging from neuro-oncology, Parkinson's disease, Alzheimer's disease, obsessive-compulsive disorder, and epilepsy (Table 1). This review provides an update of MRgFUS research in the preclinical and clinical realm within the last decade, and describes the challenges ahead and future directions for the field.
Schematic of intracranial regions targeted by MRgFUS in published human studies on an axial T1 and T2 weighted 3 Tesla MR images. OCD = obsessive compulsive disorder; MDD = major depressive disorder; PD = Parkinson's disease; ET = essential tremor; NP = neuropathic pain
Table 1 List of clinical trials investigating neurological applications of MRgFUS by disorder
The application of MRgFUS to movement disorders has been among the most promising to date. Targets for movement disorder symptoms, such as tremor, are near the geographic center of the skull in key motor relay nuclei, making these amenable to heating with minimal heating of the overlying skull. In addition, the ability to monitor patient symptoms in real-time, and evaluate the impact of a lesion on tremor, provides a powerful behavioral assay on which to base treatment decisions. To date, essential tremor (ET) and Parkinson's Disease (PD) have been the primary applications, owing in large part to the large experience with these conditions in the ablative neurosurgical literature.
Approximately 4% of people over 40 years of age are affected by essential tremor, which is marked by postural and intention tremors of about 4–7 Hz [6]. In some patients, these tremors can be severe enough to affect daily activities such as eating, drinking, and writing. 15–25% of patients are forced to retire prematurely as a result of ET, and 60% of patients do not apply for jobs or promotions due to uncontrollable shaking [7]. First-line therapy for ET is medical, typically with propranolol and primidone. However, one third of the patients will find the side effects of these medications intolerable or have refractory symptoms. Alternative treatments for ET includes surgical targeting of the ventral intermediate nucleus (Vim) of the thalamus. The Vim is part a circuit that connects the cerebellum with cortical motor pathways important for tremor. While deep brain stimulation electrodes are implanted bilaterally [8], the target contralateral to the more disabled side is treated in radiofrequency (RF) ablation to minimize severe neurological complications [9]. These two modalities are the most well-established interventions in the treatment of ET. While they are effective, both involve cranial access, which carries a risk of infection and hemorrhage. The rates of infection, seizures, and intracranial hemorrhage after DBS, which may be taken as correlates to brain penetration, are 1.7%, 1.5% and 3.9% respectively [10]. Device-related issues such as hardware breakage, mal-placement or migration, and battery depletion make life-long maintenance necessary for DBS. Gamma knife radiosurgery is another ablative technique. Despite being noninvasive, radiosurgery is less favorable because the results are variable and delayed often requiring weeks to months to become noticeable.
Two pilot studies of focused ultrasound Vim ablation were published in 2013 demonstrating promising clinical results after MRgFUS thalamotomy [11, 12]. In one study of fifteen patients, the Clinical Rating Scale for Tremor (CRST) score improved by 74% at 12 months (p = 0.001) and disability score by 85% at 12 months (p = 0.001) [11]. A subsequent multicenter randomized sham control trial in 76 patients with ET showed that MRgFUS treatment was superior to placebo with 47% improvement in hand-tremor score at 3 months and 62% reduction in disability score [4]. More recently, Zaaroor et al. reported their experience with MRgFUS thalamotomy in thirty patients with tremor across a wide-range of disorders (18 with ET, 9 with PD and 3 with ET-PD) [13]. At six-month follow-up, patients with ET had a significant decrease of CRST score from 40.7 to 8.2; patient with PD or ET-PD had a significant decrease in motor component of PDQ-39 from 38.6 to 20.6. Quality of Life in Essential Tremor (QUEST) score similarly improved. Common adverse events following MRgFUS thalamotomy include paresthesia, taste disturbances, headaches, and reported sense of imbalance. While pin site discomfort from the stereotactic frame is common, no infection has been reported so far. More serious complications such as ataxia are approximately 1.6% [5]. Zaaroor et al. reported that all neurological complications improved by three months after treatment [13].
Parkinson's disease (PD) is the second most common neurodegenerative disorder, with a prevalence of approximately 50 per 100,000 people at 65 years of age [14]. PD is characterized by motor symptoms such as tremor, bradykinesia, and rigidity, with tremor present in 50% of patients at the time of diagnosis [15]. Motor symptoms are caused by the progressive death of dopaminergic neurons in the substantia nigra pars compacta (SN) [16], and although a wide range of medications are used to manage PD, dopamine replacement is the mainstay of treatment. For patients who become refractory to medical treatment neurosurgical intervention may be appropriate, targeting critical motor nuclei that are pathophysiologically linked to the core motor symptoms of PD. Currently, the most widely practiced surgical treatment is DBS of subcortical motor structures, the globus pallidus internus (GPi) and subthalamic nucleus (STN) [10, 17]. While DBS is the gold-standard surgical approach to refractory PD that is still responsive to levodopa, the operation may not be suitable for every patient, nor every symptom. For example, older patients are often excluded from DBS, and the procedure may not be suitable for those who cannot undergo general anesthesia, or who suffer from levodopa induced dyskinesia. Accordingly, there is growing interest and experience in MRgFUS for PD, as an alternative to DBS and other open ablative procedures, such as RF pallidotomy [15]. Various targets have been proposed for MRgFUS ablation to treat tremor-dominant PD in early clinical studies, including the pallidothalamic tract [18], Vim thalamus, [13, 19, 20], and GPi [21]. The optimal target in PD is unclear, and will depend on the symptomology of the patient. Recent studies in PD patients treated with MRgFUS, report clinical significant improvement in motor symptoms after treatment ranging from 61% reduction in Unified PD Rating Scale (UPDRS) motor score at 3 months for pallidothalamic tractomy [18] to 46.2% at 6 months for Vim thalamotomy [13]. However, different methodologies and outcome measures make direct comparison difficult (For detailed discussion see Schlesinger et al. [15]). Future studies will need to compare outcomes after MRgFUS ablation compared to placebo or current surgical treatment options for tremor-dominant PD.
The potential of low intensity ultrasound in conjunction with microbubbles to safely and transiently open the blood brain barrier (BBB) has also attracted considerable interest by PD researchers. The BBB is the brain's primary defense against large (> 400 Da) and hydrophilic molecules. Small molecules and certain drugs can pass through the BBB through diffusion or receptor mediated cellular transport [22]. However, the BBB has hampered therapeutic development for various neurological disorders such as PD and Alzheimer's disease (AD) [23].
Multiple animal studies have shown that ultrasound mediated BBB disruption is temporary, reversible within hours, and safe to surrounding tissue at appropriately selected ultrasound parameters [24]. Interactions between ultrasound and pockets of gas or injected microbubbles lead to inertial cavitation, oscillations of the microbubbles, resulting in mechanical force on tight junctions and endothelial cells [25]. The extent of the BBB opening depends on the microbubbles (e.g. size, conjugates) as well as ultrasound parameters (e.g. intensity, sonication time) [26]. Preclinical studies ranging from mouse to nonhuman primates have demonstrated the safe delivery of macromolecules [27], viruses [28], and substances as large as cells [29, 30].
Randomized control trials of direct intraparenchymal inoculation of neurotrophic agents, such as glial cell-derived neurotrophic factor (GDNF), or embryonic dopamine neurons in degenerating dopaminergic pathways have largely failed to date [31,32,33]. One possible explanation could be inadequate delivery of therapeutic compounds across the blood brain barrier [34]. A growing preclinical MRgFUS literature has demonstrated increased intraparenchymal concentration of growth factors, stem cells, and gene therapy after BBB opening [30, 35,36,37]. In one study, done in a 6-OHDA model of PD, MRgFUS delivery of GDNF resulted in significantly higher levels of dopamine and less abnormal apomorphine-induced rotational behavior than after direct intraparenchymal infusion of GDNF [35].
Neuropathic pain (NP) is complex, multifactorial, and difficult to treat. NP can originate from a dysfunction in the nervous system due to disease, injury, or iatrogenic causes. Prevalence of chronic pain with neuropathic features in the general population may be as high as 8% [38]. Primary management includes tricyclic antidepressants (TCAs), selective serotonin-norepinephrine reuptake inhibitors (SSRIs), anti-epileptic medications, and opioids, which may result in intolerable side effects and tolerance over time [39]. Various surgical strategies have been developed to treat chronic pain, including cordotomy, sympathectomy, myelotomy, dorsal root entry zone lesions, mesencephalotomy, and cingulotomy, depending largely on the nature of the pain, it's location, and previous treatment attempts [40]. Ablative procedures in the thalamus have also been performed for several decades [41], and now MRgFUS offers a less invasive alternative. In one study, central lateral thalamotomy using MRgFUS in 12 patients suffering from chronic medically-refractory NP reported mean pain relief of 57% at 12 months [42]. Further clinical trials are underway to investigate the effects of MRgFUS thalamotomy for neuropathic pain (NCT01699477).
Obsessive-compulsive disorder (OCD) is among the most challenging and debilitating anxiety disorders, with an estimated lifetime prevalence of 1.6% [43]. OCD is marked by unwanted intrusive, recurrent, and persistent thoughts, images, or urges that are often accompanied by time-consuming and repetitive behaviors. OCD has been linked to various neurochemical and neuroanatomical pathways, including hypersensitivity of post-synaptic serotonin receptors, and mutations in serotonin transporter and receptor genes [44,45,46,47]. Accordingly, first-line treatment has typically focused on brain chemistry, using selective serotonin reuptake inhibitors or tricyclic antidepressants such as clomipramine, paired with psychotherapeutic interventions, such as exposure and cognitive behavioral therapy [48]. However, despite optimal care, up to 30 to 40% of patients remain significantly disabled [49, 50]. Recent imaging, preclinical, neuropsychological, and treatment studies have increasingly supported the view that OCD is a disorder of neural circuitry [51]. For treatment resistant patients, therefore, surgical approaches which target specific brain regions and circuitry, may be an emerging option.
The anterior limb of the internal capsule (ALIC) has been closely associated with the surgical management of refractory OCD [52]. The ALIC contains a rich network of fibers that connect both the prefrontal cortex and anterior cingulate cortex with the hippocampus, amygdala, and thalamus [53,54,55]. Disruption of these tracts is believed to be important in treating refractory OCD, by disrupting limbic cortico-thalamic fibers affecting depression and anxiety and influencing circuits critical for emotion and affective processing [53,54,55,56,57]. A meta-analysis of DBS and open label prospective anterior capsulotomy studies in patients with refractory OCD found a 51% reduction on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) after ablation (radiofrequency and gamma-knife radiosurgery) compared to 40% after DBS [58]. Furthermore, individuals who underwent the ablative therapy were 9% more likely to go into remission than DBS. A recent systematic review of eight observational studies with a total of 112 patients after AC showed a mean reduction of 55% on the Y-BOCS at 12 months, superior to results from meta-analysis of outcomes after dorsal anterior cingulotomy [59].
Non-invasive approaches to capsulotomy include gamma knife radiosurgery (GKRS) and MRgFUS. GKRS uses ionizing radiation for incision-less ablation, but results have a latency period of weeks to months [60]. Additional concerns about exposure to ionizing radiation include risk of neoplasm and injuries to off target structures [61]. The effect of MRgFUS is immediate, permitting real-time monitoring of the lesion and the temperature required to achieve it. Jung et al. reported the proof-of-concept study of bilateral thermal capsulotomy using MRgFUS in four patients with medically refractory OCD [62]. Gradual improvements in Y-BOCS score were noted over 6 months, with an ultimate mean improvement of 33%. These patients also had comorbid major depressive disorder. Over the same period, patients experienced sustained reductions in symptoms of depression (mean 61.1%) and anxiety (mean 69.4%). No adverse effects or significant differences in neuropsychological test scores were noted. This result is promising, but durability of the outcome, cumulative safety profile, and its value over placebo or traditional nonablative methods (e.g. DBS) and ablative methods (e.g. GKRS) will require further investigations.
The development of MRgFUS ablation as a therapy for other psychiatric illnesses are also underway. The first MRgFUS procedure for treatment-resistant major depressive disorder (MDD) showed initial safety and improvement in the Hamilton Depression Rating Scale score from 26 pre-procedure to 7 at 12 months, Beck Depression Inventory score from 26 to 12 at 12 months [63]. The lesion target for treatment-resistant MDD is also ALIC. This single case report demonstrated marked clinical improvement. Two clinical trials (NCT02348411, NCT02685488) are currently underway to further define the role of ultrasound in depression.
The most common brain tumors, metastatic and glioblastoma multiforme (GBM), have prognoses of 3 [64] and 4 months survival, respectively, if left untreated [65]. Indeed, despite advances in genetics and concerted multidisciplinary efforts in developing new therapeutics, the gains in patient survival have been modest. With modern treatment, the median overall survival of patients with GBM is only 14.6 months [66]. Tumors in eloquent or deep brain regions are poor candidates for surgical resection and, though traditionally treated with radiotherapy, may benefit from alternative modalities now under investigation, including proton beam radiation and laser interstitial thermal therapy (LITT) [67]. MRgFUS may represent an additional option.
Focused ultrasound thermoablation of bone metastases, prostate cancer, and uterine fibroids are approved by the FDA [34, 68, 69]. At temperatures above approximately 55 °C, tumor tissue shows homogenous coagulative necrosis leading to irreversible cell death [70]. Early clinical studies of MRgFUS thermoablation for brain tumors have predominantly focused on high-grade gliomas. McDannold et al. published the first experience with sonication of high-grade glioma through the intact skull [71]. While the procedure proceeded without any complications seen in previous studies (e.g. thermal injury in the pre-tumor area), coagulative necrosis was not achieved due to insufficient power. As such, the adjustments including doubling the number of transducer elements, decreasing the frequency from 650 kHz to 230 kHz and increasing the power capabilities were made to the system. Unfortunately, the fourth patient suffered a post procedure intracranial hemorrhage, which was linked to possible underlying coagulopathy and inertial cavitation. This complication highlighted the challenges of ablating a large volume and vascular neoplastic tissue as well as greater attention to patients or pathologies with increased risk of hemorrhage. Currently phase I trials (NCT01698437, NCT00147056, NCT01473485) are underway with results pending.
Targets located close to the skull are difficult to thermoablate without unacceptable rise in temperature in bone, scalp, or neighboring neurovascular structures. Recently, two proof of concept animal studies of non-thermal ablation of skull base lesions were reported. McDannold et al. demonstrated that low-duty cycle sonication at 525 kHz with intravenously injected microbubbles can produce lesions at the skull base close to the optical nerve in rats [72]. Sonicated microbubbles undergo inertial cavitation, leading to vascular injuries and ischemic necrosis in the target. Evidence from histology and evoked potential data supports preservation of the optic nerve. This study was replicated in nonhuman primates using MRgFUS operating at 220 kHz, low duty cycles and intravenous Definity® microbubble contrast [73]. However, off-target effects included unintentional BBB opening, particularly in the pre-tumor area. Further safety studies are necessary to examine the tradeoff to this approach, a greater risk of inertial cavitation along the acoustic path [74].
Blood brain barrier disruption for chemotherapy delivery
While tumor cells can break down the blood barrier, they also infiltrate into surrounding tissue resulting in angiogenesis and blood vessels with an intact BBB [75]. A majority of chemotherapies have limited bioavailability in the brain and tumor tissue. Additionally, while targeted therapies for specific cancers (e.g. trastuzumab for HER2 positive breast cancer and vemurafenib, BRAF kinase inhibitor, for melanoma) have dramatically changed the prognosis of patients without intracranial metastasis, these drugs poorly penetrate the BBB [76, 77]. As a result, several attempts have been made to couple chemotherapy with transient opening of the BBB. For example, simultaneous intra-arterial administration of mannitol and carboplatin or bevacizumab infusion has been examined in early clinical trials to treat high grade gliomas [78]. In addition to mixed and modest outcomes, patients were exposed to potential complications from the endovascular procedure and neurotoxicity from nonspecific brain uptake of the chemotherapy. MRgFUS offers a less invasive approach to open the BBB transiently with enhanced spatial and temporal specificity.
An early animal study demonstrated successful and safe delivery of trastuzumab in mouse [27]. In another study, ultrasound mediated BBB opening plus temozolomide (TMZ) administration compared to TMZ alone in rats with implanted 9 L glioma cells reduced 7-day tumor progression and extended median survival from 20 to 23 days [79]. CSF-to-plasma ratio of TMZ level was increased by 1.7 times. In another study, eight treatments of ultrasound delivered NK-95 cells in mice injected with human HER2-expressing breast tumor resulted in an increase in overall survival from approximately 50 to 150 days [29]. As the result of compelling preclinical data, a pilot trial is underway to investigate safety and feasibility of ultrasound mediated BBB disruption for patients with high-grade gliomas to deliver TMZ (NCT02343991).
Alzheimer's disease (AD) is the most common neurodegenerative disease, affecting more than five million people in the United States, and increasing. The pathologic hallmarks of AD consist of beta-amyloid plaques and neurofibrillary tangles resulting in synaptic dysfunction and neurodegeneration. Current FDA approved medications, anti-cholinesterase inhibitors and NMDA receptor antagonist, have only modest clinical benefit. Alternatively, biologic agents, such as bapineuzumab and solanezumab, aim to improve clearance of Aβ plaques and oligomers [80]. While they have proven to be effective both histologically and behaviorally in animal models and early clinical trials, there has yet to be an immunotherapy proven to be clinically effective in phase 3 clinical trials [81, 82].
As with PD and Brain tumors, the BBB is a major obstacle to the effective delivery of potential therapeutic compounds to AD brains, and MRgFUS has been explored as a possible means to overcome it. In a transgenic mouse model of AD, treated with ultrasound delivered, anti-BAM, an antibody against Ab plaque, to a single hemisphere results in a reduction of plaque number and surface area by more than 20% compared to the contralateral hemisphere after four days [83]. After treatment, transgenic animals performed as well as wild-type animals on the Y maze task, suggesting a rescue of spatial memory deficits. Surprisingly, BBB opening alone also led to a significant plaque reduction. Increased endogenous IgG and IgM antibodies bound to beta amyloid plaques and glial activation after BBB opening suggests that the influx of endogenous antibodies can lead to activation of the innate immune system against the pathologic plaques. Moreover, an increased hippocampal neurogenesis was found after sonication, which may also contribute to the memory rescue.
Reductions in plaque number and surface area after ultrasound mediated BBB opening alone were replicated by another research group in APP23 transgenic mouse line [84], along with behavioral improvement as well as a five-fold reduction of Aβ monomer and two-fold reduction of Aβ trimer, which may have an even greater role in AD pathogenesis. More recently, the same group demonstrated ultrasound delivered RN2N, an antibody to tau, reduced phosphorylated tau levels in a transgenic TauP301L mouse [85]. The presence of neurofibrillary tangles and hyper-phosphorylated tau are closely correlated with the progression of cognitive deficits in patients with AD. An ongoing phase I trial will study the feasibility and safety of BBB opening in patients with mild Alzheimer's disease (NCT02986932).
Conclusion and future directions
MRI guided focused ultrasound can be used at high and low intensities for neuroablation, opening the BBB and potentially neuromodulation. We reviewed the clinical applications of neuroablation and BBB opening that are established or currently under investigation in human studies. Although promising, several challenges exist for brain applications of MRgFUS. For example, targets close to the skull are challenging to treat with high frequencies, given the bone heating that results from the large amount 0of energy necessary to achieve coagulative necrosis. Non-thermal ablation may circumvent this problem [72], although the experience is preliminary and can be associated with unintended off-target changes (e.g. BBB opening) [6].
Further, the relative efficacy of MRgFUS ablation for tremor, and other indications such as OCD, compared to traditional open surgical approaches will need to await longer follow-up and larger clinical experiences. Current treatment times require several hours in the MRI machine, and improvements in sonication protocol and workflow are needed to decrease treatment time and enhance tolerability. Similarly, technologic advances eliminating the need for complete head shave and the use of a stereotactic frame, will contribute to making the procedure more tolerable for patients.
Basic scientists will continue to study how ultrasound interacts with tissue. Questions exist as to the chronic changes to the neurovascular unit after BBB opening and how they will affect repeat treatments. A recent study reported that ultrasound mediated BBB opening leads to a sterile inflammatory reaction [86]. Although inflammation is expected after mechanical opening of the BBB and may in fact contribute to clearance of beta amyloid plaques, further studies are needed to quantify the cellular and molecular genetics changes from BBB opening at minimal energy settings. On the clinical front, researchers are exploring the potential of combining MRgFUS mediated BBB opening with drugs or biologic agents. In doing so, FUS could be a valuable tool in treating a wide range of neurological conditions, such as neurodegenerative diseases and demyelinating diseases, but phase I studies will need to first establish the safety and feasibility of BBB opening in these populations. As research teams are poised to translate existing animal data to human studies in the next decade, there remains promise that intracranial MRgFUS can have an increasingly important role in the management of the most challenging brain conditions.
BBB:
blood brain barrier
CRST:
clinical rating scale for tremor
DBS:
FUS:
focused ultrasound
GDNF:
glial cell line derived neurotrophic factor
GKRS:
gamma knife radiosurgery
GPi:
globus pallidus interna
LITT:
laser interstitial thermal therapy
MDD:
MRgFUS:
magnetic resonance image guided focused ultrasound
QUEST:
quality of life in essential tremor
RF:
SN:
TMZ:
UPDRS:
unified Parkinson's disease rating scale
Vim:
ventral immediate nucleus of the thalamus
Y-BOCS:
Yale-Brown Obsessive Compulsive Scale
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Kovacs ZI, Kim S, Jikaria N, Qureshi F, Milo B, Lewis BK, et al. Disrupting the blood-brain barrier by focused ultrasound induces sterile inflammation. Proc Natl Acad Sci U S A. 2017;114:E75–84.
Available data and materials
No funding was used for the creation of this manuscript.
Division of Neurosurgery, Department of Surgery, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON, Canada
Ying Meng, Suganth Suppiah, Michael L. Schwartz & Nir Lipsman
Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada
Karim Mithani, Benjamin Solomon & Nir Lipsman
Ying Meng
Suganth Suppiah
Karim Mithani
Benjamin Solomon
Michael L. Schwartz
Nir Lipsman
MLS, NL, and YM conceived of the idea for this manuscript. All authors contributed to writing of the manuscript. YM, KM, and BS helped format the table and figure. All authors read and approved the final manuscript.
Correspondence to Ying Meng.
Dr. Lipsman has served as a paid consultant on expert steering committees for Focused Ultrasound Foundation, which is a non-profit organization that promotes the use of image-guided focused ultrasound. YM, SS, KM, BS, and MLS have no conflicts of interest or financial disclosures.
Meng, Y., Suppiah, S., Mithani, K. et al. Current and emerging brain applications of MR-guided focused ultrasound. J Ther Ultrasound 5, 26 (2017). https://doi.org/10.1186/s40349-017-0105-z
MRI guided focused ultrasound
MRgFUS
Neuroablation
Blood-brain barrier disruption

redpajama_set_name: RedPajamaCommonCrawl


The College has received outstanding results in the Excellence in Research for Australia (ERA) 2018 assessment.
Study at the best. ANU is ranked #1 in Australia and #20 in the world according to the QS World University Rankings 2018/19.
Be job-ready. ANU is ranked first in Australia and 21st in the world for Graduate Employability according to the Global University Employability Ranking 2017.
Be innovative. ANU offers unique, modern degrees designed to meet the challenges of the future - preparing you for success in today's changing world.
The demand for engineering and computer science graduates is growing across all industries, business and government. By studying at the College of Engineering and Computer Science you will gain the skills, knowledge and experience to successfully compete in today's evolving job market.
Conduct high-quality research under the supervision of a world-class academic. The College offers research supervision in a wide range of areas.
Join a dynamic and pioneering research environment where you can pursue your interests alongside some of the world's brightest and most innovative researchers. Get an opportunity to collaborate with an extensive network of academic, government, and industry partners in Australia and worldwide, and gain the skills to enable change in today's complex world.
Read about the latest initiatives, ground-breaking research and outstanding individuals within the College of Engineering and Computer Science. Attend an upcoming event or seminar and take part in the many opportunities available at the College.
A group of six ANU College of Engineering and Computer Science students have been announced as the winners of the ZeroCO2 Renewable Energy & Sustainability Hackathon.
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This 2,625 square foot cottage is a classic coastal home with a modern twist and a wide open floor plan. Built as a retirement home on the coast of Maine, the house was designed with a future elevator in mind and a first floor master suite. A large bank of divided light windows in the great room provide excellent views towards the ocean and a roaring fire makes the cozy dining area even more comfortable.


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Simpler Video Game Menus Are Better
Stephen Totilo
Filed to: game designFiled to: game design
yoshi's woolly world
The release of the former Wii U exclusive Yoshi's Woolly World to the Nintendo 3DS demonstrates once again that gaming menus are best when they're lists. Nothing fancier is needed. We don't need to be able to wander every which way through them.
Both versions of Woolly World are sidescrollers. They pretty much have the same levels. But the Wii U game presents its menus on a walkable 2D plane. The 3DS game presents them as straight lines. Guess which one is more convenient to use?
Here's the main menu of the Wii U version of the game. In it, you must walk Yoshi around a circular area, going from a hut for swapping Yoshis to another hut for doing Amiibo stuff and so on.
Here is the new 3DS version of that, all laid out in one nice straight line...
Another example: This is how you pick which of the game's levels you want to play. Yoshi's got to walk to each one wandering around a little field:
And here's how they do it in the 3DS version...
There no doubt that the Wii U game is prettier. Its menu areas look way nicer than the 3DS game's. But menus aren't about looking pretty. They're about showing you your options and letting you get to stuff quickly.
Sometimes 2D is better than 3D. In this case, give me a 1D menu over a 2D one any day.
Editor-in-Chief. Currently playing: Division 2, AC Odyssey, Baba Is You and Outer Wilds (need to get back to RDR2, Destiny 2, Iconoclasts, Arkham Origins, Doom, Sushi Striker, Samus Returns & Chasm)
Recent from Stephen Totilo
Assassin's Creed Odyssey's New Atlantis Expansion Is Jaw-Dropping
Okay, Seriously, Maybe VR Gaming Is About To Have Its Big Moment
The Division 2's next big content update, which includes two new story missions and a more puzzle-oriented challenge called…


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Dit is de lijst van de premiers van Noord-Korea:

Premiers van Noord-Korea (1948-heden)

Zie ook
 Lijst van staatshoofden van Noord-Korea
 Lijst van Secretarissen-Generaal van de Koreaanse Arbeiderspartij
 Lijst van voorzitters van de Nationale Defensiecommissie van de Democratische Volksrepubliek Korea

Noord-Korea

Geschiedenis van Noord-Korea
Premiers

redpajama_set_name: RedPajamaWikipedia


Emily Carlaw's work employs printmaking and watercolours to explore ideas of femininity through the juxtaposition of fragility and grace with power and purpose. Her works pays homage to the past, evoking a feeling of nostalgia that is heavily influenced by strong and creative female role models she has encountered in her life from great women of the past, storybook characters, her grandmother, mother and younger sister.
Her current series Floral Fables shares stories of coming of age while celebrating sisterhood and friendship along with a touch of romance. You can find Emily and more of her work in her small shop called Freckles and Porcelain which is located in St Peters, PEI.
Please drop into Artisan on Main Souris to see and purchase Emily's work.


¡Hola y bienvenidos a la página de web de Señora O'Donnell. This website is designed to give Conemaugh Township students information about their Spanish courses throughout the school year. This website will be updated on a weekly basis, providing important information regarding homework, classwork, upcoming tests, and quizzes.


Did you know that the average American now consumes a whopping 50 gallons per person per year of sugar- sweetened beverages? This is the second highest consumption rate in the world (after Mexico), equivalent to approximately 1.5 cans of soda per person per day!
Sugar sweetened beverages are the leading source of added sugar in the American diet. Besides having no nutritional value, SSBs displace healthier beverage options. They are cheap and readily avaialble, and they are one of the most widely advertised products, particularly to children and low income groups. The United States in in the midst of an obesity epidemic. Americans are among the most overweight and obese population in the world.
There is a strong link between the amount and frequency of sugar consumed and dental cavities. The primary cause of dental cavities is a diet high in sugar, and the primary source of sugar in our children's diets is sugary drinks. These are products that we should prevent our children and youth from drinking.


Premium training, desirable locations and charming resort hotels designed to fulfill your CRNA continuing education requirements.
CRNA Anesthesia conferences, fully accredited by the AANA, starting as low as $250. Take a trip for both business and pleasure.
Relax & learn in beautiful Wine Country! Book your hotel early ~ it's Harvest Time!!
Cornerstone Anesthesia Conferences is based in Houston, Texas, which is home to the largest medical center in the United States and many world-renowned medical complexes. Founded in 2016 by CRNAs and for CRNAs, our mission is to serve as the foundation for excellence in continuing anesthesia education services.
Cornerstone Anesthesia Conferences focuses on offering the most up-to-date, evidence-based information, with all of our lectures pertaining to the Core Modules of the CPC Requirements. Our topics are hand-picked to correspond with all of the four Core Modules. To that end, we offer world class speakers and cutting edge topics in exciting, fun-filled locations with opportunities for networking, meeting other CRNAs, and relaxing while learning. Join us at one of our CRNA seminars today!
Are you a CRNA who wants to be at the top of your field?
Are you a CRNA who takes pride in your work?
Are you a CRNA who values continuing education?
Are you a CRNA who is uncompromising in your professional development?
If this fits your description, then... Cornerstone Anesthesia Conferences is for you!!


The rainy season has arrived, as well as the annual flood cycle that is currently taking place, especially in areas such as Jakarta. Many places into flood-prone point so that a barrier of access roads. Flooding that occurred a few days ago made a lot of motorcyclists and car experiencing similar problems, namely "strike machine". Not just about the vehicle, but the access to go to work or return back home run into obstacles, such as access roads are cut off due to flooding, the time taken for a long time and yet another vehicle died as a result of stagnant water flood into the engine. This is certainly a difficulty when it occurs in a relatively long time is not it?
When floods, exhaust motors fully submerged in a pool of water, it would not be turned back, because water has entered into the gas tank. But it is different if only a little water in, so that the engine while the vehicle is still able to neutralize these conditions. Therefore the first step is to drain the water that has entered into the motor exhaust to dry.
The cause of the motor broke down shortly be due to two things, namely, motorcycle carburetor flooding penetration of water so that the water mixes with fuel vehicles that cause the motor broke down and the motor plugs are wet, so that the spark plug that has a function as a cigarette lighter flame when exposed to flood water will strike because of wet. To perform drainage in your carburetor can open sewer gas in your motor, cast the correct amount of gasoline in the carburetor float.
Then for motorcycle spark plugs, you can take it off for a while to wipe with a dry cloth to miss the spark plugs and plug parts, so that plugs can return to function properly. Once this is done, you can re-install the spark plug and perform the manual for your motor starter, this step is to warm up the engine.
To ensure the condition of your motor really in good shape, a good idea to also check the electrical system on your bike, if there is a short circuit occurs or not. After that to maintain the performance of your motorcycle can also clean your bike dirty from all the dirt and mud attached when the floods hit.
In this case, the brake drum and brake pads plays an important role, because when braking suddenly when they want to do you can control your balance or hold the brake to break through the flood when using gear 1. Therefore, you should also clean the two components is to actually clean. However, if the condition of brake pads is up, you should immediately change your motorcycle brake pads with new ones, to keep the performance of your motorcycle to pre-flood.


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HomeQJ.NETXbox 360The agents of Crackdown
The agents of Crackdown
After the deluge of screenshots from Crackdown that we had yesterday, many may have noticed that there are various "heroes" or lead characters in the screens, ranging from a black guy, to a goth-looking character. So, we decided to take a short break to get to know these characters a bit more.
In total, there are eight types of agents to choose from, with each one changing their looks as they get stronger when the player progresses in the game. Out of the eight types, the people over at Real Time Worlds have made it a point to avoid the "typical" hero image which depicts someone who is tall, dark, handsome and white. As a result, we have the African American, Asian, Russian, Goth, Norse, Maori, Thai, and Hispanic agents, all of whom possess their own distinguishing traits.
The African American agent is inspired by the character Blade, and as an homage to the said character, this agent has the same hair style. The Russian agent on the other hand, was inspired by a character from the Highlander film, "Kurgen". The Goth agent proved to be a slight challenge as the designers didn't want him to look like a member of KISS, so they decided to go with the pasty look but use facial hair patterns instead in order to show the character's level and rank. The other agents all bear some trait which shows their heritage, even though these traits may be slightly stylized.
So, in a place like Pacific City, the last thing that you need would be an dull agent. The agents of Crackdown however, all have the personality, as well as the arsenal, to go head-to-head with whatever crime lords have got to throw at them.
Mod: Xbox 360 Nightlight
Crackdown 2 vidoc is "nothing sacred", just pure mayhem
Halo 3: the release date guessing game


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Indonesia Volcano Erupts
Volcano Erupts in Indonesia Causing Evacuation
Logan Fast, Writer
Early Sunday morning on December 4th, 2022 the Semeru volcano in Indonesia erupted causing a layer of thick gray ash to cover the entire sky for miles on the eastern part of Java Island. This ended up leaving 1,900 people evacuated and unplaced, hundreds are reported injured with the count rising. The Semeru volcano's last major eruption occurred as recently as December 2021, a disaster that killed more than 50 people and injured hundreds more.
New York Times written by The New York Times reports that local authorities from the B.N.P.B (National Agency for Disaster Countermeasure), Indonesia's disaster mitigation agency, have not received any reports of casualties but said that personnel from an array of agencies had performed search and rescue checks through Sunday evening. The B.N.P.B. said that the Center for Volcanology and Geological Hazard Mitigation had also raised the alert level for Mount Semeru to level IV, the highest possible category. More than 20,000 face masks have been handed out to mitigate respiratory health risks from volcanic ash.
CNN writers Maseru Jamaluddin and Kareem El Damanhoury, report that the agency warned all citizens to stay at least 10 miles away from the eruption site and added the fact that the ash had reached at least 7 miles away from the epicenter. Indonesia, an archipelago of 270 million people, sits on the "Ring of Fire," a band around the Pacific Ocean that sets off frequent earthquakes and volcanic activity. Standing at 3,676 meters (12,060 feet), Mount Semeru is the tallest volcano on Java — and one of its most active ones.
Also reported by CNN, a statement from PVMBG chief Hendra Gunawan said the agency saw the potential for a larger volume of magma from the eruption Sunday.
"Therefore Semeru's hot clouds could reach further (this year) and at that distance there are many residences," he said.
Semeru, also known as Mahameru, has erupted numerous times in the last 200 years. Still, as is the case with many of the 129 active volcanoes in Indonesia, tens of thousands of people continue to live right next to the volcano. Eruptions are a lot easier to predict than the past, however it can not always be relied on, according to NPR.org.
Logan Fast
Logan is a sophomore at Northmont high school. This is her first year in journalism. She plays soccer, basketball, and track.
WHAT IS THE BEST HALLOWEEN MOVIE
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A gentleman doesn't follow trends. A gentleman invests in a number of staple items that form the backbone of his wardrobe. I use the term 'invest' because I am a firm believer that increasing your budget to allow for higher quality craftsmanship and materials will always pay off in the long run.
Below I've given a succinct overview of the absolute suiting necessities any successful man has in his wardrobe.
The staple suits in a man's wardrobe are influenced by occasion just as much as the need for versatility. Formal occasions such as funerals still command a simple, single-breasted black suit. Though commonly seen as a dated and plain suit, there's nothing more timeless than a gentleman who can perfectly execute the simplest of tasks.
Versatility. The navy suits sit on the verge of casual and formal wear allowing you to move seamlessly from the office to the bar. The masculine blue colour matches perfectly with most colours and is an easy go-to option for every day use. A navy suit matched with a crisp white shirt should be a staple outfit for every man.
Like the navy, a very wearable colour commonly seen in the office. The formality of this colour is more powerful than a navy suit and a perfect way to mix up your office wardrobe, particularly on a day full of meetings.
The Double-Breasted Suit is the best example of why a suit should be tailored. A well-cut Double-Breasted hugs the waistline, giving a powerful, hour glass like figure to the gentleman who wears it. This cut is already a bold statement, so as a staple its best to keep your first Double-Breasted simple with a plain colour and subtle, or no pattern.
In the Australian climate, a lightweight suit needs to be at your disposal. Choosing a breathable fabric such as linen, cotton or seersucker will allow you to stay cool throughout the day when the heat turns up. A slightly shorter cut on the leg and the addition of a cuff allows for a pair of loafers to be worn and ultimately cool you down.
Black Tie occasions are the few times in the year where everyone is expected to look their very best. For any gentleman, this task is relatively simple, the first step is to ensure you have a perfectly cut tuxedo. We have some great customisations that give a nod to tradition but also provide a unique and personal edge.


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Toyota Drivers Claim Championship In The World Endurance Championship
Stef Schrader
Filed to:WEC
Sebastien Buemi and Anthony Davison, drivers of the number 8 Toyota TS040, were crowned LMP1 drivers' champions in the 6 Hours of Bahrain, the penultimate race of the World Endurance Championship. Congratulations, Team We're Not Audi!
The #8 car only finished in 11th place, but that was enough to give Buemi and Davison the championship.
Toyota's other LMP1, the #7 car, was driven to victory, granting driver Mike Conway his first LMP1 win. Alexander Wurz and Stephane Sarrazin rounded out the competent trio of drivers.
If you're tired of Audi domination year after year (or you just want some kind of rival), this season gives some hope for 2015. Porsche's two LMP1 cars rounded out the podium in second and third place, with Audi's cars finishing in fourth and fifth. Let's not forget how down-to-the-wire Le Mans was this year, either. Next year is going to be fun.
LMP1 wasn't the only championship that was decided in Bahrain. In GTE Pro, Gianmaria Bruni and Toni Vilander claimed the drivers' championship in the #51 AF Corse Ferrari 458. AF Corse also claimed the teams' championship at this race.
While Aston Martin Racing couldn't eke out a win over AF Corse in GTE Pro, Aston Martin drivers Kristian Poulsen and David Heinemeier-Hansson claimed a drivers championship in GTE Am.
The final round of the World Endurance Championship takes place on November 30 at Interlagos in Brazil. LMP2's titles are still up for grabs, so expect insanity there.


Body armours and special/ structured costume realization and production.
Recognised specialists in principal character costume origination, in real materials, duplicates and key front of camera costume armours.
Creating in real materials, metals, moulded leathers, linens and precious metals; plus synthetics such as urethanes and polymers, all with an emphasis on costume and tailoring, comfort, fit and a beautiful finish.


The Payroll/Personnel System (PPS) is maintained by Office of the President.
This is the production payroll system accessed through TN3270 (telnet software) installed on your computer, or through a web interface.
EDB Inquiry-only screens: View current payroll / personnel employee database information.
Entry/Update screens: Perform a variety of payroll/ personnel actions such as processing new hires, transfers, enrollment to various deductions, etc.
Online Payroll Time Reporting System (OPTRS) screens: Allows entry of time data and payroll adjustment transactions.
Only authorized users can access PPS. Access is granted based on assigned job duties and requires submission of the PPS Access/Change Application and DRS PPS Structure.
Changes need to be made in the payroll system in order to be compliant by December 1, 2016. Read more for tools and assistance with conversion.
Mon–Fri, 6 a.m. – 7 p.m.
Sat, 6 a.m. – 6 p.m.


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Former lobbyist Preston Padden looking for spectrum sellers
By Joe Flint
Former Disney and News Corp. lobbyist Preston Padden is fronting a new organization for TV station owners interested in participating in the Federal Communications Commission's efforts to buy broadcast spectrum that it can auction off to wireless companies.
So far, few broadcasters have publicly expressed a desire to sell either some or all of their spectrum. The FCC wants the spectrum because it fears there is a shortage looming given the explosion of mobile devices, especially in big cities. The spectrum has been valued at $25 billion and the potential cut for TV stations is $1.75 billion.
Many broadcasters have said there is no such shortage but the industry has agreed to take part in a voluntary spectrum auction.
The organization, dubbed the "Expanding Opportunities for Broadcasters Coalition," said its founding members "include television broadcast stations that under the right conditions, would like to participate in the auction." Padden declined to say which broadcasters he is working with, citing the confidentiality requirements of the FCC's auction process.
Padden, who retired from Walt Disney Co. in 2009 and is now a senior fellow and adjunct professor at the University of Colorado Law School, said in an interview Tuesday that he was drawn to the position because "this is going to be one of the most interesting telecom issues of the next few years."
He added that "if the auction is going to be a success, it has to be structured in a way that entices willing broadcasters to participate."
There were mumblings around Washington soon after the Padden announcement came out that the organization was in fact being funded by the wireless communications industry.
Padden called such speculation "ridiculous" and "completely made up."
ALSO:FCC votes to start spectrum auction process
FCC gets greenlight to sell spectrum
Disney lobbyist Preston Padden to step down
Follow Joe Flint on Twitter @JBFlint.
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Joe Flint is a former staff writer for the Los Angeles Times.
'Ted Lasso' isn't just a TV show. It's a vibe
From a stoned Amsterdam monologue to a pair of sports coverage TV ads to a newly beloved sitcom, 'Ted Lasso' isn't just a show. It's a vibe.
Tyler Perry and MPTF to get humanitarian award at Oscars
Filmmaker Tyler Perry and the Motion Picture and Television Fund are being honored with the Jean Hersholt Humanitarian Award, the Academy of Motion Picture Arts and Sciences said Thursday
Spike Lee had never heard of Golden Globe Ambassadors — until his kids became them
Ahead of Spike Lee accepting the American Cinematheque Award, the filmmaker tells The Times about his kids' historic Golden Globes gig and Chadwick Boseman.
SAG Awards rescheduled again: A new April date makes way for the Grammys in March
The 2021 Screen Actors Guild Awards, already postponed once, are moved to April 4 after briefly sharing a March 14 air date with the rescheduled Grammy Awards.
All the dates for 2021's trippy awards show season
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Carrie Coon delves into the dynamics of marriage in 'The Nest'
Spending time with a toddler and 'Piranha' has been a boon to the actress.


This isn't something new, seen it around pretty much any android/sense update since I started doing this. This is just a starting point to finding how to fix it.
Recommended read: Upgrades, what you should do.
How can I tell if it's a bug or not? If you do a factory reset and it's STILL there and it can be replicated on other phones with the same software number: congrats! you've got a bug!
Why do I then have problems? It can simply be apps/etc that doesn't fully agree with the new update. If you have 245 apps installed, and none of them are from Play store: that might be a small hint. It's often something small things that causes it, and often very simple: apps installed. Not always though I should point out. Sometimes on carrier/network phones their "additions" can just mess with things a lot. But, it's still worth it to do a factory reset to just "shake things down".
So what do I do? I use a 4 step process myself. Or some of them.
Simply press power button (volume up and power button on One M8) for 10 seconds with phone on and active, it will do a countdown after 7 seconds. And will after that do a nice clean restart. This you use if phone crash as well and just doesn't respond as well.
Can it be other things? with other fixes? Of course it can be. It's rarely big complex problems, it's often the small ones.
You've tried ANYTHING you've seen and it still doesn't work? That might be hardware, best to talk with HTC support.


What is inflammation and why is it so important to reduce it?
There are two kinds of inflammation. The first is the body's response to an injury such as falling on a knee and having it swell as part of the healing response. The second is whole-body inflammation, which refers to chronic, imperceptible, low-level inflammation.
Studies suggest that over time this kind of inflammation sets the foundation for many serious, age-related diseases including heart disease, cancer and neurodegenerative conditions such as Alzheimer's and Parkinson's diseases.
Please refer to this study about inflammation and Alzheimer's.
Replace processed foods with fresh vegetables and some fresh fruit. (more on this later).
Eat a Low glycemic index foods (no processed, "white" foods etc.) which means that it is important to stop eating refined, processed and manufactured food.
Eat enough dietary fiber daily.
Consume Arginine rich foods (fish, nuts) regularly.
Move your body, get some physical activity daily.
Replace processed foods with fresh vegetables and some fresh fruit.
The "Father of Medicine", Hippocrates said, "Let thy food by thy medicine, and thy medicine be thy food." Sound advice indeed.