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OECD Home DigitalBy Date
Business advice for entrepreneurship and small firms
This paper reviews issues and trends in business advice policies for business start-ups and existing SMEs, including public support for business consultancy and mentoring. Business advice policies aim to improve the growth, survival and productivity performance of new and small firms by strengthening their strategic management capabilities. The paper examines the rationale for government policies in this field, different policy delivery models, recent policy trends - such as increased use of third party delivery and performance management systems - and evidence on policy impacts. It focuses in particular on three key issues faced by policy makers - how to stimulate demand for business development services from firms and entrepreneurs who could benefit; how to target and segment support provided to different types of firms and entrepreneurs; and how to introduce digital business diagnostic tools into the advice system.
5-March-2021
Delivering Quality Education and Health Care to All - Preparing Regions for Demographic Change
COVID-19 has put renewed focus on the importance of addressing longstanding challenges that OECD governments face in delivering public services, especially in regions with people spread over a wider area where economies of scale are more difficult to achieve. The physical infrastructure needed to provide good quality education and health services can be more complex and expensive in rural and remote regions that also struggle to attract and retain education and health care professionals. Acute ageing trends in many rural regions and, in some cases, a shrinking population will require sustainable policy responses that will need to be coherent with pressure to drive efficiencies in public spending. This report examines the nuances specific to the delivery of education and health care to people everywhere, offering recommendations on how to better adapt provision to the realities of today and the emerging realities of tomorrow to face the challenges of distance, demographic change and fiscal belt-tightening. The report also examines digital connectivity issues in rural and remote regions, recognising the significant scope for digital delivery of services to mitigate challenges related to distance. Finally, the report looks at governance issues, including fiscal issues, through which the delivery of these critical services is administered and paid for.
AI measurement in ICT usage surveys - A review
This paper takes stock of official statistics on AI use in firms collected through ICT usage surveys. Its aim is to highlight statistically sound data that can be used to guide policymakers and other stakeholders in the complex field of AI. It provides a cross-country comparison of official AI measures in selected OECD countries and international organisations by reviewing the statistical AI definitions developed explicitly for measurement purposes as well as the AI questions in official ICT use surveys. Based on the results of these surveys, the paper provides an international comparison of AI uptake among firms. It also includes a brief overview of smaller-scale non-official measures of AI, which can complement official statistics. In its final part, it makes an initial attempt to match AI policy with the AI measures previously analysed, and highlights possible next steps. This paper is also a contribution to the OECD AI Policy Observatory.
Encouraging vulnerability treatment - Overview for policy makers
Most digital security incidents are caused by malicious actors (e.g. cybercriminals and state-sponsored groups) exploiting vulnerabilities in organisations' digital ecosystems. Addressing vulnerabilities before attackers take advantage of them is an effective means of reducing the probability of cybersecurity incidents. This paper discusses vulnerabilities in products' code such as software and firmware, and in how products are implemented in information systems. It shows that the technical community has progressed in developing good practice for treating vulnerabilities, including through co-ordinated vulnerability disclosure (CVD). However, significant economic and social challenges prevent stakeholders from adopting good practice, such as legal frameworks that do not sufficiently protect 'ethical hackers' from legal proceedings. The paper stresses that public policies aimed at removing obstacles and encouraging vulnerability treatment could significantly reduce digital security risk for all. The findings from this paper will inform the development of a new OECD Recommendation in this area.
Going Digital in Latvia
Going Digital in Latvia analyses recent developments in Latvia's digital economy, reviews policies related to digitalisation and make recommendations to increase policy coherence in this area, based on the OECD Going Digital Integrated Policy Framework. The review uses strategic foresight to explore three alternative future scenarios, which could result from the digital transformation of the global economy and society. It also examines the availability and quality of communication networks and services in Latvia as well as related policies and regulations. Further, it reviews trends in digital technology usage among individuals, businesses and the government, and examines policies to foster diffusion. Finally, the review analyses opportunities and challenges raised by digitalisation in key areas, from innovation and skills to digital security and data governance, and evaluates policy responses to these changes in Latvia.
Digitalizācija Latvijā
Science, technology and innovation in the time of COVID-19
Science, technology and innovation (STI) have played a key role in responding to the COVID-19 pandemic and the unprecedented socio-economic crisis it has triggered. This paper explores how the pandemic affected STI in 2020, including how STI was mobilised to provide vaccines, treatments and innovative (often digital) solutions to address 'social distancing'. The paper also reviews the quick and agile STI policy responses implemented across countries to stimulate research and innovation activities to find solutions to the pandemic. Moreover, the paper covers STI policies that targeted universities, research centres, innovative businesses and entrepreneurs most affected by the crisis. It also raises key debates on the effectiveness of such policies. Follow-up work will leverage more and better data to improve this early assessment of the impacts of the crisis and STI policy responses.
9-February-2021
Understanding the digital security of products - An in-depth analysis
Economies and societies are increasingly reliant upon 'smart products' that contain code and can connect to one another, e.g. through the Internet. Recent cyber-attacks such as Mirai, WannaCry, NotPetya and SolarWinds have underlined that the exploitation of vulnerabilities in smart products can have severe economic and social consequences. Such attacks increasingly threaten users' safety and well-being, as well. This report shows that economic factors play an important role in the relative 'insecurity' of smart products. It develops an analytical framework based on the value chain and lifecycle of smart products, and applies the framework to three case studies: computers and smartphones, consumer Internet of Things (IoT) devices and cloud services. It demonstrates that complex and opaque value chains lead to a misallocation of responsibility for digital security risk management, while significant information asymmetries and externalities often limit stakeholders' ability to behave optimally.
Enhancing the digital security of products - A policy discussion
From 'traditional' software to cloud services and Internet of Things (IoT) devices, our economies and societies are increasingly reliant upon 'smart products' that contain code and can connect to each other, e.g. through the Internet. Such products are vulnerable to cyber security risk, and economic factors often play a major role in their relative 'insecurity'. This report discusses how policy makers can address key challenges that prevent smart products from reaching an optimal level of digital security. Increasing transparency and information sharing, promoting co-operation (including at the international level), and ensuring the duty of care of supply-side actors (e.g. through the principles of security-by-design, security-by-default and responsible end-of-life) are important avenues for policy action. Policy makers can leverage many tools to achieve these objectives, from public procurement, certification and multi-stakeholder partnerships, to labels and ex ante legal requirements.
Inclusive Growth Review of Korea - Creating Opportunities for All
In recent years Korea has stepped up efforts to reduce inequalities in recognition that a fairer economic model is also the most sustainable one. In order to support this new policy direction, the OECD has carried out novel analysis of inclusive growth building on its Framework for Policy Action, developed by the OECD to improve the prospects of the groups left behind. The Inclusive Growth Review of Korea applies, for the first time, the Framework at the national level. Using a dashboard of indicators, the Framework presents policy recommendations to sustain and more equitably share the gains of economic growth by investing in people left behind, supporting business dynamism and inclusive labour markets, and building efficient and responsive governments. In addition, the Inclusive Growth Review of Korea finds that digitalisation risks to compound the disparities of Korean labour markets, and calls for renewed efforts to reduce the lack of opportunities for up- and re-skilling of the working-age population (Chapter 2). To improve the business environment, Korea should address the unbalanced growth across sectors and firm size and unequal distribution of productivity gains across population groups (Chapter 3).
The Digital Transformation of SMEs
Despite potentially tremendous benefits, small and medium-sized enterprises (SMEs) lag in the digital transformation. Emerging technologies, as diverse as they are, offer a range of applications for them to improve performance and overcome the size-related limitations they face in doing business. However, SMEs must be better prepared, and stakes are high. SMEs make the most of the industrial fabric in many countries and regions, they create jobs (most jobs sometimes) and are the cement of inclusive and sustainable societies. The SME digital gap has increased inequalities among people, places and firms, and there are concerns that the benefits of the digital transformation could accrue to early adopters, further broadening these inequalities. Enabling SME digitalisation has become a top policy priority in OECD countries and beyond. The report looks at recent trends in SME digital uptake, including in the context of the COVID-19 crisis. It focuses on issues related to digital security, online platforms, blockchain ecosystems, and artificial intelligence. The report identifies opportunities, risks of not going digital, and barriers to adoption. It looks to concrete policy action taken worldwide to speed the SME transformation and raises a series of considerations to advance the SME digital policy agenda.
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The Opposition Opportunity
As the aftershocks from last night's political earthquake continue to make themselves felt, we saw another remarkable tremor this morning: a crazy hour in which three party leaders resigned. There is a possibility that a fourth, Natalie Bennett, may follow before the day is out – although given the Green Party had set its sights rather low given their chequered campaign, perhaps she will yet be spared.
Regardless, it must be unprecedented for three party leaders, including the official opposition, and the third and fourth parties at the general election, to see their leaders depart so rapidly and in such short order. Nigel Farage had already indicated that if he didn't win in Thanet South he would go. But the predictions of the BBC's exit poll last evening would have been enough to see Clegg and Miliband out of the door too, and the situation has only worsened for both men since it was first broadcast.
The implications for the parties are clear. All of them will have to run leadership elections, with the methods employed to find the next leader varying wildly between Labour, Lib Dems and UKIP. However, more important is the potential impact on our democracy, and the decision-making process in Parliament.
While the narrative in today's media is undoubtedly triumphalist for David Cameron, who will be enjoying every moment of his victory, that covers over the probability that the next two years – let alone the next five – will be fraught with challenges. A small Conservative majority of around 10 means that Cameron will have to manage his Parliamentary Party with an iron fist. This is something he has persistently failed to do over his first term, with frequent rebellions causing real damage to government policy. What's more, these have often been self-inflicted; the result of too many clever-clever Parliamentary games played by the whips, especially since Michael Gove took over as Chief Whip.
The likelihood is that Cameron will find himself hampered by this "awkward squad", much as John Major was frustrated by "the bastards" in 1992-1997. The challenge of maintaining discipline will be such that compromises and concessions are a regular feature within the Conservatives, even if outwardly it appears as though the party is united. Nowhere will this be more apparent than on the EU referendum, which now looms large and it is likely that Cameron will come under serious pressure from a big chunk of his MPs to move it forward.
The importance of a strong and effective opposition – whether from one or multiple parties – should therefore be obvious. By taking positions that are intelligent but critical, opposition parties should be able to make life difficult for a government on such a small majority, potentially convincing enough backbenchers to rebel to force amendments or even vote down legislation. But how can this be achieved given both the weakness of Labour and the Lib Dems, and the restrictions inherent in the SNP's position as a nationalist party no longer in its expected position of negotiating strength?
That question is one that those parties will actively be considering, even as they prepare to weigh up the options for the next phase of their political journeys. But they will also need help. New leaders tend to want to impose their own policy agenda and ideas on their parties. Given the parlous state of party finances for both Labour and the Lib Dems, the involvement of external organisations, businesses and thought-leaders in shaping policy development will be critical. There should therefore be substantial opportunities for pressure to be brought to bear and ideas to be sold in as the new hierarchies and structures become clear over the next few months. The same goes, of course, for the government backbenchers who will find that their votes are critical to the success of the Conservatives' policy agenda.
GK Strategy provides services to assist in identifying and developing such opportunities. These can be of real benefit, whether to individual businesses or charities, or to entire industries that have perhaps failed previously to gain the kind of traction they deserve. If you would like to know more, please feel free to contact us.
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Adam Berry plays Lee in dark comic romance Delicious which is set for UK release on June 30th.
Written and directed by Tammy Riley-Smith, the film follows Stella, an obsessive dieter who embarks upon a dysfunctional romance with aspiring French chef Jacques. Recently released from prison, Jacques arrives in London and starts working in the kitchen of volatile chef Victor Elwood – a man he believes could be his father. It is in the city that he meets his neighbours, feisty OAP Patti and the beguiling Stella whom the newcomer plans to seduce with his culinary talent. The only problem is she shows very little interest in Jacques and even less in his food.


On the 27th June, 1997, a research report was published in the prestigious scientific journal 'Science' that would change the world of Parkinson's disease research forever.
And I am not exaggerating here.
The discovery that genetic variations in a gene called alpha synuclein could increase the risk of developing Parkinson's disease opened up whole new areas of research and eventually led to ongoing clinical trials of potential therapeutic applications.
Todays post recounts the events surrounding the discovery, what has happened since, and we will discuss where things are heading in the future.
It is fair to say that 1997 was an eventful year.
In world events, President Bill Clinton was entering his second term, Madeleine Albright became the first female Secretary of State for the USA, Tony Blair became the prime minister of the UK, and Great Britain handed back Hong Kong to China.
In the world of entertainment, author J. K. Rowling's debut novel "Harry Potter and the Philosopher's Stone" was published by Bloomsbury, and Teletubbies, South Park, Ally McBeal, and Cold Feet (it's a British thing) all appeared on TV for the first time, amusing and entertaining the various age groups associated with them.
Musically, rock band Blur released their popular hit song 'Song 2' (released 7th April), "Bitter Sweet Symphony" by the Verve entered the UK charts at number 2 in June, and rapper Notorious B.I.G. was killed in a drive by shooting. Oh, and let's not forget that "Tubthumping" (also known as "I Get Knocked Down") by Chumbawamba was driving everybody nuts for its ubiquitous presence.
And at the cinemas, no one seemed to care about anything except a silly movie called Titanic.
Here at the SoPD we understand and are deeply sympathetic to the frustration felt by the Parkinson's community regarding the idea of '200 years and still no cure'.
As research scientists, we are in the trench everyday – fighting the good fight – trying to find ways of alleviating this terrible condition. And some of us are also in the clinics, interacting with sufferers and their families, listening to their stories and trying to help. While we do not deal directly with the day-to-day trials of living with Parkinson's disease, we are keenly aware of many of the issues and are fully invested in trying to correct this condition.
In our previous post – made in collaboration with Prof Frank Church of the Journey with Parkinson's blog – we listed the major historical milestones and discoveries made in the Parkinson's disease field during the last 200 years.
The most striking feature of that time line, however, is how just little actually happened during the first 100 years.
In fact for most of that period, Parkinson's disease wasn't even called 'Parkinson's disease'.
Of the 48 events that we covered on that time line, 37 of them have occurred in the last 50 years (26 since 2000).
Taking this line of thought one step further, 2017 is also the 20 year anniversary of the discovery of alpha synuclein's association with Parkinson's disease. And what a remarkable 20 years that has been. In 1997, a group of researcher at the National institute of Health led by Robert Nussbaum reported the first genetic mutation in the alpha synuclein gene that infers vulnerability to Parkinson's disease.
identified multiple additional mutations within that same gene that increase the risk of developing Parkinson's disease.
determined which forms of alpha synuclein are toxic.
identified alpha synuclein as an important component of Lewy bodies – the dense clusters of protein found in the Parkinsonian brain.
discovered numerous methods by which alpha synuclein can be passed between cells – potentially aiding in the spread of Parkinson's disease.
developed and validated models of Parkinson's disease based on manipulations of alpha synuclein (including numerous genetically engineered mice, viral over-expression models, etc).
identified alpha synuclein in the lining of the gut of people with Parkinson's disease and this has aided us in developing new theories as to how the condition may start.
set up and run numerous clinical trials targeting alpha synuclein (and we eagerly await the results of those trials).
published over 6200 scientific papers (don't believe me? Click here) – that's over 300 publications per year!
And the truly amazing part? All of these particular achievements are only dealing with just the one gene: alpha synuclein.
Since the identification of the alpha synuclein mutations, we have subsequently discovered genetic mutations in over 20 other genes that increase the risk of developing Parkinson's disease. And we have conducted the same activities/experiments for most of those genes as we have for alpha synuclein.
For example, in 2004 we discovered that people with genetic mutations in a gene called glucocerebrosidase (or GBA) had an increased risk of developing Parkinson's disease. In 2016, just 12 years after that discovery we have started a clinical trial designed specifically for those people (Click here for more on this).
We here at the SoPD are fully supportive of campaigns like #WeWontWait, and this post was not written (nor meant to be taken) as an excuse response to the '200 years and no cure' frustration. I can understand how it may be read that way, but I did not know how else to write it. And I thought it needed to be written.
The point of this entire post is that those 200 years need to be put into context.
And while all of these words aren't going to make life easier for someone living with Parkinson's to deal with their situation, in addition to raising awareness this week I think it is important for the Parkinson's community to also understand just how far we have come, and how fast we are currently progressing.
The question can be asked: will this be the last major anniversary we acknowledge with regards to Parkinson's disease?
I sincerely think that there is cause to hope that it is.
I have a good friend – let's call him Matt.
As a young boy, Matt remembers his grandfather having Parkinson's disease. He remembers growing up watching the trials and tribulations that the old man went through with the condition. There were basically no treatment options when Matt's grandfather was diagnosed and little in the way of support for the family. His grandfather's body simply froze up as the disease progressed. L-dopa probably only became available to Matt's grandfather during the latter stages of the disease.
Four years ago Matt's father was diagnosed with Parkinson's disease.
Thanks to scientific advances, however, Matt's dad now has a wide range of treatment options on the medication side of things. The disease can be managed so that he can still play his golf and enjoy his retirement – in a way that his own father never could. He also has numerous surgical options once those medications lose their effectiveness (eg. deep brain stimulation, Pallidotomy, etc). The chances are very likely that Matt's father will pass on by natural causes before he requires many of those additional options.
This is the progress that we have made.
But there is still a lot of work to be done of course.
During a lunch shortly after his father's diagnosis, Matt looked squarely across the table at me. Me, the Parkinson's researcher. All of the usual jovial nature was missing from his face and he simply muttered the words 'hurry up'.
Whether he was speaking for his father, himself or his own young kids, I understood where his words were coming from and the sentiment.
And, as this post and the previous post point out, we are hurrying up.
For today's post, we have teamed up with Prof Frank Church from the Journey with Parkinson's blog to bring readers an 'Introduction to the historical timeline on Parkinson's disease'.
The idea for this project started as a conversation between Frank and his partner Barbara during a recent weekend at the beach in North Carolina.
However, to complete this project Frank felt it necessary to bring in some extra help in the form of a Parkinson's expert.
And when everyone else said they were too busy, Frank contacted us.
Truly flattered, we immediately said yes. And the rest is history.
We are happy to present the milestones in Parkinson's disease research and discover, though we do apologise to the clinicians, scientists, health-care specialists, and their projects that were not cited here but we limited the timeline to ~50 notations.
Below there are six panels outlining different stages of the history of Parkinson's disease, and under each of them we have briefly described each of the events in the panel.
In 1811, Mr James Parkinson of no. 1 Hoxton Square (London) published a 66 page booklet called an 'An Essay on the Shaking Palsy'. At the date of printing, it sold for 3 shillings (approx. £9 or US$12). The booklet was the first complete description of a condition that James called 'Paralysis agitans' or shaking palsy. In his booklet, he discusses the history of tremor and distinguishes this new condition from other diseases. He then describes three of his own patients and three people who he saw in the street.
Widely considered the 'Father of modern neurology', the importance of Jean-Martin Charcot's contribution to modern medicine is rarely in doubt. From Sigmund Freud to William James (one of the founding fathers of Psychology), Charcot taught many of the great names in the early field of neurology. Between 1868 and 1881, Charcot focused much of his attention on the 'paralysis agitans'. Charcot rejected the label 'Paralysis agitans', however, suggesting that it was misleading in that patients were not markedly weak and do not necessarily have tremor. Rather than Paralysis Agitans, Charcot suggested that Maladie de Parkinson (or Parkinson's disease) would be a more appropriate name, bestowing credit to the man who first described the condition. And thus 70 years after passing away, James Parkinson was immortalized with the disease named after him.
British neurologist Sir William Gowers published a two-volume text called the Manual of Diseases of the Nervous System (1886, 1888). In this book he described his personal experience with 80 people with Parkinson's disease in the 1880s. He also identified the subtle male predominance of the disorder and provided illustrations of the characteristic posture. In his treatment of Parkinson's tremor, Gower used hyoscyamine, hemlock, and hemp (cannabis) as effective agents for temporary tremor abatement.
In the Parkinsonian brain there is a severe reduction in the chemical dopamine. This chemical was first synthesised in 1910 by George Barger and James Ewens at the Wellcome labs in London, England.
One of the cardinal features of Parkinson's disease in the brain is the presence of Lewy bodies – circular clusters of protein. In 1912, German neurologist Friedrich Lewy, just two years out of medical school and still in his first year as Director of the Neuropsychiatric Laboratory at the University of Breslau (now Wroclaw, Poland) Medical School discovered these 'spherical inclusions' in the brains of a people who had died with Parkinson's disease.
The first brain structure to be associated with Parkinson's disease was the substantia nigra. This region lies in an area called the midbrain and contains the majority of the dopamine neurons in the human brain. It was in 1919 that a Russian graduate student working in Paris, named Konstantin Tretiakoff, first demonstrated that the substantia nigra was associated with Parkinson's disease. Tretiakoff also noticed circular clusters in the brains he examined and named them 'corps de Lewy' (or Lewy bodies) after the German neurologist Friedrich Lewy who first discovered them.
The most complete pathologic analysis of Parkinson's disease with a description of the main sites of damage was performed in 1953 by Joseph Godwin Greenfield and Frances Bosanquet.
Until the late 1950s, the chemical dopamine was widely considered an intermediate in the production of another chemical called norepinephrine. That is to say, it had no function and was simply an ingredient in the recipe for norepinephrine. Then in 1958, Swedish scientist Arvid Carlsson discovered that dopamine acts as a neurotransmitter – a discovery that won Carlsson the 2000 Nobel prize for Physiology or Medicine.
In 1957, a nonprofit organisation called the Parkinson's Disease Foundation was founded by William Black. It was committed to finding a cure for Parkinson's Disease. Since its founding in 1957, PDF has funded more than $115 million worth of scientific research in Parkinson's disease.
In 1960, Herbert Ehringer and Oleh Hornykiewicz demonstrated that the chemical dopamine was severely reduced in brains of people who had died with Parkinson's disease.
Knowing that dopamine can not enter the brain and armed with the knowledge that the chemical L-dopa was the natural ingredient in the production of dopamine, Oleh Hornykiewicz & Walther Birkmayer began injecting people with Parkinson's disease with L-dopa in 1961. The short term response to the drug was dramatic: "Bed-ridden patients who were unable to sit up, patients who could not stand up when seated, and patients who when standing could not start walking performed all these activities with ease after L-dopa. They walked around with normal associated movements and they could even run and jump." (Birkmayer and Hornykiewicz 1961).
In 1967, Melvin Yahr and Margaret Hoehn published a rating system for Parkinson's disease in the journal Neurology. It involves 5 stages, ranging from unilateral symptoms but no functional disability (stage 1) to confinement to wheel chair (stage 5). Since then, a modified Hoehn and Yahr scale has been proposed with the addition of stages 1.5 and 2.5 in order to help better describe the intermediate periods of the disease.
In 1968, Greek-American scientist George Cotzias reported dramatic effects on people with Parkinson's disease using oral L-dopa. The results were published in the New England Journal of Medicine. and L-dopa becomes a therapeutic reality with the Food and Drug Administration (FDA) approving the drug for use in Parkinson's disease in 1970. Cotzias and his colleagues were also the first to describe L-dopa–induced dyskinesias.
When given alone levodopa is broken down to dopamine in the bloodstream, which leads to some detrimental side effects. By including an aromatic amino acid decarboxylase (AADC) inhibitor with levodopa allows the levodopa to get to the blood-brain barrier in greater amounts for better utilisation by the neurons. In the U.S., the AADC inhibitor of choice is carbidopa and in other countries it's benserazide.
Dopamine agonists are 'mimics' of dopamine that pass through the blood brain barrier to interact with target dopamine receptors. Since the mid-1970's, dopamine agonists are often the first medication given most people to treat their Parkinson's; furthermore, they can be used in conjunction with levodopa/carbidopa. The most commonly prescribed dopamine agonists in the U.S. are Ropinirole (Requip®), Pramipexole (Mirapex®), and Rotigotine (Neupro® patch). There are some challenging side effects of dopamine agonists including compulsive behaviour (e.g., gambling and hypersexuality), orthostatic hypotension, and hallucination.
In the late-1970's, monoamine oxidase-B (MAO-B) inhibitors were created to block an enzyme in the brain that breaks down levodopa. MAO-B inhibitors have a modest effect in suppressing the symptoms of Parkinson's. Thus, one of the functions of MAO-B inhibitors is to prolong the half-life of levodopa to facilitate its use in the brain. Very recently in clinical trials, it's been shown that MAO-B inhibitors have some neuroprotective effect when used long-term. The most widely used MAO-B inhibitors in the U.S. include Rasagiline (Azilect) and Selegiline (Eldepryl and Zelpar); MAO-B inhibitors may reduce "off" time and extend "on" time of levodopa.
After successful preclinical experiments in rodents, a team of researchers in Sweden, led by Anders Bjorklund and Olle Lindvall, began the first clinical trials of fetal cell transplantation for Parkinson's disease. These studies involved taking embryonic dopamine cells and injecting them into the brains of people with Parkinson's disease. The cells then matured and replaced the cells that had been lost during the progression of the disease.
In July of 1982, Dr. J. William Langston of the Santa Clara Valley Medical Center in San Jose (California) was confronted with a group of heroin addicts who were completely immobile. A quick investigation demonstrated that the 'frozen addicts' had injected themselves with a synthetic heroin that had not been prepared correctly. The heroin contained a chemical called MPTP, which when injected into the body rapidly kills dopamine cells. This discovery provided the research community with a new tool for modelling Parkinson's disease.
The gene Parkin provides the instructions for producing a protein that is involved with removing rubbish from within a cell. In 1998, a group of Japanese scientists identified mutations in this gene that resulted in affected individuals being vulnerable to developing a very young onset (juvenile) version of Parkinson's disease.
Using the injection of a small amount of radioactive material (known as a tracer), the level of dopamine present in an area of the brain called the striatum could be determined in a live human being. Given that amount of dopamine in the striatum decreases over time in Parkinson's disease, this method of brain scanning represented a useful diagnostic aid and method of potentially tracking the condition.
In 1991, actor Michael J Fox was diagnosed with young-onset Parkinson's disease at 29 years of age. Upon disclosing his condition in 1998, he committed himself to the campaign for increased Parkinson's research. Founded on the 31st October, 2000, the Michael J Fox Foundation has funded more than $700 million in Parkinson's disease research, representing one of the largest non-governmental sources of funding for Parkinson's disease.
In 2003, German neuroanatomist Heiko Braak and colleagues presented a new theory of how Parkinson's disease spreads based on the postmortem analysis of hundreds of brains from people who had died with Parkinson's disease. Braak proposed a 6 stage theory, involving the disease spreading from the brain stem (at the top of the spinal cord) up into the brain and finally into the cortex.
DJ1 (also known as PARK7) is a protein that inhibits the aggregation of Parkinson's disease-associated protein alpha synuclein. In 2003, researchers discovered mutations in the DJ1 gene that made people vulnerable to a early-onset form of Parkinson's disease.
A small open-label clinical study involving the direct delivery of the chemical Glial cell-derived neurotrophic factor (GDNF) into the brains of people with Parkinson's disease indicated that neuroprotection. The subjects involved in the study exhibited positive responses to the treatment and postmortem analysis of one subjects brain indicated improvements in the brain.
Early onset Parkinson's is defined by age of onset between 20 and 40 years of age, and it accounts for <10% of all patients with Parkinson's. Genetic studies are finding a causal association for Parkinson's with five genes: alpha synuclein (SNCA), parkin (PARK2), PTEN-induced putative kinase 1 (PINK1), DJ-1 (PARK7), and Leucine-rich repeat kinase 2 (LRRK2). However it happens, and at whatever age it occurs, there is no doubt that genetics and environment combine together to contribute to the development of Parkinson's.
In 2006, Japanese researchers demonstrated that it was possible to take skin cells and genetically reverse engineer them into a more primitive state – similar to that of a stem cell. This amazing achievement involved a fully mature cell being taken back to a more immature state, allowing it to be subsequently differentiated into any type of cell. This research resulted in the discoverer, Shinya Yamanaka being awarded the 2012 Nobel prize for Physiology or Medicine.
The Movement Disorder Society (MDS) unified Parkinson's disease rating scale (UPDRS) was introduced in 2007 to address two limitations of the previous scaling system, namely a lack of consistency among subscales and the low emphasis on the non-motor features. It is now the most commonly used scale in the clinical study of Parkinson's disease.
Postmortem analysis of the brains of people with Parkinson's disease who had fetal cell transplantation surgery in the 1980-1990s demonstrated that Lewy bodies are present in the transplanted dopamine cells. This discovery (made by three independent research groups) suggests that Parkinson's disease can spread from unhealthy cells to healthy cells. This finding indicates a 'prion-like' spread of the condition.
Our understanding of the genetics of Parkinson's is rapidly expanding. There is recent evidence of multiple genes linked to an increase the risk of idiopathic Parkinson's. Interestingly, microtubule-associated protein tau (MAPT) is involved in microtubule assembly and stabilization, and it can complex with alpha synuclein (SNCA). Future therapies are focusing on the reduction and clearance of alpha synuclein and inhibition of Lrrk2 kinase activity.
The ability to generate dopamine cells from skin cells derived from a person with Parkinson's disease represents not only a tremendous research tool, but also opens the door to more personalized treatments of suffers. Induced pluripotent stem (IPS) cells have opened new doors for researchers and now that we can generate dopamine cells from people with Parkinson's disease exciting opportunities are suddenly possible.
Exercise has been shown to be both neuroprotective and neurorestorative in animal models of Parkinson's. Exercise promotes an anti-inflammatory microenvironment in the mouse/rat brain (this is but one example of the physiological influence of exercise in the brain), which helps to reduce dopaminergic cell death. Taking note of these extensive and convincing model system results, many human studies studying exercise in Parkinson's are now also finding positive benefits from strenuous and regular exercise to better manage the complications of Parkinson's.
In 2010, a European research consortium began a clinical study with the principal objective of developing an efficient and safe treatment methodology fetal cell transplantation in people with Parkinson's disease. The trial is ongoing and the subjects will be followed up long term to determine if the transplantation can slow or reverse the features of Parkinson's disease.
Scientists in Sweden and New York have successfully generated dopamine neurons from human embryonic stem cells that can be successfully transplanted into animal models of Parkinson's disease. Not only do the cells survive, but they also correct the motor deficits that the animals exhibit. Efforts are now being made to begin clinical trials in 2018.
Several research groups have found the Parkinson's disease-associated protein alpha synuclein in the lining of the gut, suggesting that the intestinal system may be one of the starting points for Parkinson's disease. In 2016, researchers found that the bacteria in the stomachs of people with Parkinson's disease is different to normal healthy individuals. In addition, experiments in mice indicated that the bacteria in the gut can influence the healthy of the brain, providing further evidence supporting a role for the gut in the development of Parkinson's disease.
Isradipine is a calcium-channel blocker approved for treating high blood pressure; however, Isradipine is not approved for treating Parkinson's. In animal models, Isradipine has been shown to slow the progression of PD by protecting dopaminergic neurons. This study is enrolling newly diagnosed PD patients not yet in need of symptomatic therapy. Participants will be randomly assigned Isradipine or given a placebo.
Approximately 50% of the people with Parkinson's develop psychotic tendencies. Treatment of their psychosis can be relatively difficult. However, a new drug named Nuplazid was recently approved by the FDA specifically designed to treat Parkinson's psychosis.
Catechol-O-methyl transferase (COMT) inhibitors prolong the effect of levodopa by blocking its metabolism. COMT inhibitors are used primarily to help with the problem of the 'wearing-off' phenomenon associated with levodopa. Opicapone is a novel, once-daily, potent third-generation COMT inhibitor. It appears to be safer than existing COMT drugs. If approved by the FDA, Opicapone is planned for use in patients with Parkinson's taking with levodopa who experience wearing-off issues.
Nilotinib (Tasigna® by Novartis) indicates positive results in phase I trial.
Nilotinib is a drug used in the treatment of leukemia. In 2015, it demonstrated beneficial effects in a small phase I clinical trial of Parkinson's disease. Researchers believe that the drug activates the disposal system of cells, thereby helping to make cells healthier. A phase II trial of this drug to determine how effective it is in Parkinson's disease is now underway.
International Stem Cell Corporation is currently conducting a phase I clinical cell transplantation trial at a hospital in Melbourne, Australia. The company is transplanting human parthenogenetic stem cells-derived neural stem cells into the brains of people with Parkinson's disease. The participants will be assessed over 12 months to determine whether the cells are safe for use in humans.
Neuropore Therapies is a biotech company testing a compound (NPT200-11) that inhibits and stablises the activity of the Parkinson's disease-associated protein alpha synuclein. This alpha-synuclein inhibitor has been shown to be safe and well tolerated in humans in a phase I clinical trial and the company is now developing a phase II trial.
Prexton Therapeutics recently announced positive phase I clinical trial results for their lead drug, PXT002331, which is the first drug of its kind to be tested in Parkinson's disease. PXT002331 is a mGluR4 PAM – this is a class of drug that reduces the level of inhibition in the brain. In Parkinson's disease there is an increase in inhibition in the brain, resulting in difficulties with initiating movements. Phase II clinical trials to determine efficacy are now underway.
Following remarkable results in a small phase I clinical study, the recent history of the neuroprotective chemical GDNF has been less than stellar. A subsequent phase II trial demonstrated no difference between GDNF and a placebo control, and now a second phase II trial in the UK city of Bristol has reported initial results also indicating no effect. Given the initial excitement that surrounded GDNF, this result has been difficult to digest. Additional drugs that behave in a similar fashion to GDNF are now being tested in the clinic.
Immunotherapy is a treatment approach which strengthens the body's own immune system. Several companies (particularly 'AFFiRis' in Austria and 'Prothena' in the USA) are now conducting clinical trials using treatments that encourage the immune system to target the Parkinson's disease-associated protein alpha synuclein. Both companies have reported positive phase I results indicating the treatments are well tolerable in humans, and phase II trials are now underway.
A New Zealand company called Living Cell Technologies Limited have been given permission to continue their phase II clincial trial of their product NTCELL, which is a tiny capsule that contains cells which release supportive nutrients when implanted in the brain. The implanted participants will be blindly assessed for 26 weeks, and if the study is successful, the company will "apply for provisional consent to treat paying patients in New Zealand…in 2017".
MAO-B inhibitors shown to be neuroprotective.
MAO-B inhibitors block/slow the break down of the chemical dopamine. Their use in Parkinson's disease allows for more dopamine to be present in the brain. Recently, several longitudinal studies have indicated that this class of drugs may also be having a neuroprotective effect.
Many people with Parkinson's disease have issues with swallowing. This makes taking their medication in pill form problematic. Luckily, a new inhalable form of L-dopa will shortly become available following recent positive Phase III clinical trial results, which demonstrated a statistically significant improvements in motor function for people with Parkinson's disease during OFF periods.
Exenatide is a drug that is used in the treatment of diabetes. It has also demonstrated beneficial effects in preclinical models of Parkinson's disease, as well as an open-label clinical study over a 14 month period. Interestingly, in a two year follow-up study of that clinical trial – conducted 12 months after the patients stopped receiving Exenatide – the researchers found that patients previously exposed to Exenatide demonstrated significant improvements compared to how they were at the start of the study. There is currently a placebo-controlled, double blind phase II clinical trial being conducted and the results should be reported before the end of 2017.
As I suggested at the start of this post, this endeavour was entirely Frank's idea – full credit belongs with him. I was more than happy to help him out with it though as I thought it was a very worthy project. During this 200 year anniversary, I believe it is very important to acknowledge just how far we have come in our understanding of Parkinson's disease since James first put pen to paper and described the six cases he had seen in London.
And Frank's idea perfectly captures this.
Our policy at the SoPD is not to advertise or endorse commercial products or services. This is to avoid any ethical or conflict of interest situations.
Every now and then, however, we see something that we believe will be of interest and value to the Parkinson's community…aaand we bend our policy rule book.
Today the Journal of Parkinson's disease released a "200 years of Parkinson's disease" OPEN ACCESS special issue of their journal which highlights some of the major discoveries in the field of Parkinson's disease research.
Critically, the articles provide insights into how the discoveries were made, and they are written by some of the biggest names in the Parkinson's research community (many of whom were actually there when the discoveries were made).
Click here to see all of the articles in this special issue.
We fully recommend readers take advantage of this OPEN ACCESS issue and learn about how some of these great discoveries were made.
Full disclosure: The Journal of Parkinson's disease is a product of IOS Press. The SoPD has not been approached by or made any offers to IOS Press or anyone at the Journal of Parkinson's disease. We merely thought that the material in this particular OPEN ACCESS issue would be of interest to our readers.


Starting Out is a pedagogical guide book for beginning flute teachers. It contains a comprehensive collection of proven methods for teaching beginning and progressing students, based on decades of experience. Covering all aspects of teaching the flute in the early stages, the book presents numerous teaching tips, technical explanations and problem solving ideas for the teacher.


The shipping is exclusive of any taxes, duties and extra charges from any destination country.
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text:
https://www.barrons.com/articles/drug-price-legislation-2020-election-trump-senate-house-pelosi-51569417617
Drug-Price Legislation Probably Won't Happen Before the 2020 Election. One Analyst Explains Why.
Photograph by Eric Baradat/AFP/Getty Images
With the 2020 election ticking closer and an impeachment process likely to suck up the remaining oxygen in Washington in the coming months, experts say time may have run out for drug-price legislation.
Worries about federal government efforts to place limits on drug prices have depressed biotech and pharmaceutical stocks in recent months, as President Donald Trump and the Democrats have been in rare accord in supporting limits on drug prices.
Despite a handful of proposals on the table, though, the time to get a bill through before the 2020 election may have passed.
"There is a lot of industry spin around this right now, but that notwithstanding, it is very unlikely were are going to see major legislation go through" in the near term, said Dan Mendelson, founder of Avalere Health, a health-care consulting firm, and a former official in the Office of Management and Budget during the Clinton administration.
In a note out Wednesday morning, RBC Capital Markets analyst Brian Abrahams also wrote that significant near-term policy changes seem unlikely, citing an interview with an unnamed health-care policy expert.
"Too little, too late, for federal [government] action," Abrahams wrote. "With the general election little more than a year away and other items on politicians' agendas, [our expert] expects parties to focus more on optics than on effecting real changes."
Various proposals to limit drug prices have been put forward in recent months, including one from the Senate Finance Committee and one from House Speaker Nancy Pelosi. President Trump has also pushed the issue. The S&P 500 Pharmaceuticals, Biotech & Life Sciences industry group is down 6.1% over the past 12 months, while the broader S&P 500 is up 2.4%. The iShares Nasdaq Biotechnology ETF (ticker: IBB) is down 15% over the same period, and the Dow Jones Industrial Average has gained 1.8%.
Drug companies have been fighting the pricing legislation, as The Wall Street Journal reported on Tuesday, with industry trade groups spending millions on ads opposing various legislative and regulatory efforts.
Their efforts may be working. In his note, Abrahams wrote that significant policy changes were unlikely in the near term.
Of the Senate Finance Committee bill, which Abrahams characterizes as "moderate," he said that Senate Republicans oppose some aspects. "As such, short of a push by President Trump...it appears unlikely that Sen. Majority Leader McConnell would risk the potential embarrassment of bringing a bill, which would require substantial fleshing out and revision anyway, to a vote."
The Pelosi bill, Abrahams said, will likely pass the House, but fail to pass the Republican-controlled Senate. And while Trump has pressed the drug-price issue, Abrahams said the president is unlikely to place it "at the top of his agenda."
"While our [expert] felt given his predilection for negotiations President Trump may actually be inclined to support Pelosi's House bill, given the optics around cooperation—especially now, in our view, with an impeachment investigation initiated—we believe this potentially highest-risk scenario for drugmakers is very unrealistic," Abrahams wrote.
Mendelson said that Democrats likely don't want the drug-price issue resolved before the election. "I think that given the differences in the views of the [Democratic] caucus right now...I don't see them coming to a full consensus on a bill."
He said some minor near-term changes were possible, such as a restructuring of Medicare Part D that would lower copays—a measure supported by drug companies. "That would be less about drug pricing and more about affordability for seniors," he said.
With near-term pressure relieved, the focus will turn to the postelection outlook. Members of both parties, in debates and policy discussions, highlight the issue as urgent, and many of the candidates would likely push for legislation if elected.
"The central issue is affordability," Mendelson said. "And they are not going to solve that before the 2020 election."


I have over 40 years experience as a trial attorney specializing in legal malpractice, as well as real estate. My expertise includes: attorney malpractice arising out of both litigation and transactions, with a focus on the applicable community standard of care issues; construction defects; probate and trust; real estate broker agency non disclosure issues; negligence and misrepresentation claims; breach of lease agreements; limited partnership disputes; and creditor's rights suits including obtaining writs of attachment, writs of execution, temporary restraining orders, and preliminary injunctions. I have additional expertise on attorney fee disputes; ethics in violation of the California Rules of Professional Conduct; providing expert opinions on standard of care and breach of fiduciary duty claims; real estate disputes; lease agreements; standard of care for real estate brokers; non-disclosures in real estate sales; trust litigation; and will contests. I have more than 10 years expert witness experience with consultations, deposition, and courtroom testimony.
My expert witness experience includes: Breach of fiduciary duty of loyalty; Improper drafting of settlement of injuries; Abandonment of plaintiff after settling P.I. claims; Violation of settlement agreement; Violation of Rules of Professional Conduct; Submission of the wrong contract, which was unsigned by the plaintiff; Negligence in failing to designate expert witnesses; Non-retention of an expert witness, non-disclosure of financial information, and poor cross-examination of expert witnesses; Reasonable value of fees incurred in handling a multi-year lawsuit; Lack of prosecution, failure to properly comply with NASD procedures, and violation of Business and Professions Code; Confidentiality – mishandling of jury selection, cross-examination, and burden of proof.


text:
July 7, 2019 / 3:28 PM / 10 days ago
Border agency knew of troubling Facebook posts in 2016: acting secretary
FILE PHOTO: A U.S. Customs and Border Protection patch is seen on the arm of a U.S. Border Patrol agent in Mission, Texas, U.S., July 1, 2019. REUTERS/Loren Elliott/File Photo
WASHINGTON (Reuters) - U.S. Department of Homeland Security officials knew in 2016 about a private Facebook group where border agents posted racist and misogynistic comments, acting DHS Secretary Kevin McAleenan said on Sunday.
McAleenan said on ABC's "This Week" that he had been told about an allegation in 2016 "that was investigated, followed up on, and that discipline was meted out on an agent that made an offensive post on that website."
The Customs and Border Protection (CBP) service came under fire over the issue last Monday, when the nonprofit news site ProPublica reported that offensive content had been posted on a private Facebook group for current and former CPB officers.
Posts included jokes about the deaths of migrants and sexually explicit comments referring to U.S. Representative Alexandria Ocasio-Cortez, the news outlet said.
McAleenan said the Facebook page was a private site run by a group of individuals in their off-duty hours and not under CBP control. He said DHS did put out a social media policy encouraging border agents to maintain standards and a code of conduct on social media.
When the latest Facebook posts emerged, he said he directed an immediate investigation. "It had already been reported to our inspector general. They were already looking into it," he told ABC.
Several agents have been placed on administrative duties and cease and desist letters have been sent to more, McAleenan said. "This investigation is continuing, and the agents will be held accountable if they are CBP employees who did inappropriate things," he said. "I don't think it's reflective of the men and women we have."
On Friday, the chairman the House of Representatives' Homeland Security Committee asked an internal watchdog to investigate whether top officials at DHS and CBP knew about the Facebook group.
"Such vile and threatening behavior from agents of the United States government is entirely unacceptable" and "should be grounds for immediate dismissal," U.S. Representative Bennie Thompson said in a letter to the DHS's acting inspector general.
Reporting by Doina Chiacu; Editing by Lisa Shumaker


text:
using MediatR;
using Microsoft.Extensions.Logging;
using NServiceBus;
using SFA.DAS.CommitmentsV2.Application.Commands.UpdateLevyStatusToLevy;
using SFA.DAS.EmployerFinance.Messages.Events;
using System.Threading.Tasks;

namespace SFA.DAS.CommitmentsV2.MessageHandlers.EventHandlers
{
    public class LevyAddedToAccountEventHandler : IHandleMessages<LevyAddedToAccount>
    {
        private readonly IMediator _mediator;
        private readonly ILogger<LevyAddedToAccountEventHandler> _logger;

        public LevyAddedToAccountEventHandler(IMediator mediator, ILogger<LevyAddedToAccountEventHandler> logger)
        {
            _mediator = mediator;
            _logger = logger;
        }

        public async Task Handle(LevyAddedToAccount message, IMessageHandlerContext context)
        {
            _logger.LogInformation($"LevyAddedToAccount event received for Account {message.AccountId}");
            await _mediator.Send(new UpdateLevyStatusToLevyCommand { AccountId = message.AccountId });
        }
    }
}

redpajama_set_name: RedPajamaGithub


text:
Edgar és una població dels Estats Units a l'estat de Nebraska. Segons el cens del 2000 tenia una població de 539 habitants.

Demografia
Segons el cens del 2000, Edgar tenia 539 habitants, 240 habitatges, i 150 famílies. La densitat de població era de 273,8 habitants per km².

Dels 240 habitatges en un 25,8% hi vivien nens de menys de 18 anys, en un 52,1% hi vivien parelles casades, en un 7,5% dones solteres, i en un 37,5% no eren unitats familiars. En el 34,2% dels habitatges hi vivien persones soles el 22,1% de les quals corresponia a persones de 65 anys o més que vivien soles. El nombre mitjà de persones vivint en cada habitatge era de 2,25 i el nombre mitjà de persones que vivien en cada família era de 2,87.

Per edats la població es repartia de la següent manera: un 24,1% tenia menys de 18 anys, un 5,2% entre 18 i 24, un 24,7% entre 25 i 44, un 22,3% de 45 a 60 i un 23,7% 65 anys o més.

L'edat mediana era de 42 anys. Per cada 100 dones de 18 o més anys hi havia 94,8 homes.

La renda mediana per habitatge era de 29.191 $ i la renda mediana per família de 39.286 $. Els homes tenien una renda mediana de 27.417 $ mentre que les dones 17.000 $. La renda per capita de la població era de 18.447 $. Aproximadament el 4,9% de les famílies i el 7,5% de la població estaven per davall del llindar de pobresa.

Poblacions més properes
El següent diagrama mostra les poblacions més properes.

Referències

Entitats de població de Nebraska

redpajama_set_name: RedPajamaWikipedia


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text:
To reserve the museum for your event please call to check availability.
Please fill out form to use the museum
Welcome To The Little Snake River Museum
The Little Snake River Museum is home to over 15 historic buildings and countless exhibits depicting the rich history of this secluded ranching valley. Housing thousands of artifacts, photographs, and stories, the museum has pieced together many tales of a bygone era. People who have stayed and people who have moved on have all left their mark on this valley. Come spend a day at the museum exploring their stories and get a glimpse of how they lived.
On the road to nowhere, the Little Snake River Valley is one of Wyoming's best kept secrets. Winding around ancient volcanic mountains and through lush pasture land, the Little Snake River flows westward into the drier lands of Browns Park, an area steeped in outlaw history. The valley's rich resources have drawn a variety of residents over the years: native people, explorers, trappers, settlers, homesteaders, miners, stockmen, and outlaws—they have all called this valley home. Visit the Little Snake River Museum and find out why. It's "worth the stop."
Jim Baker's Cabin
Ranching History
Antique Vehicles and Wagons
Mining and Geology
Dr. Noyes' Medical Exhibit
Hands-on Homestead House
Dude Ranch History
One-room Schoolhouse
Mountain-man Campsite
Mercantile and Laundry
Sod-roofed Cabins
Barbershop Display
Quilts and Handiwork
Blacksmithing Tools
Saddles and Tack
Saloon Display
Local-two-cell Jail
Firearms and Military Room
Turn-of-the-century Log Homes
Old-time Fashions
It has taken many years, many hands, and many minds to make the museum what it is today. We appreciate everyone who has worked, volunteered, and donated to the museum. Thank you!


WILLIAM A. STEEN & ASSOCIATES is a Consulting Civil Engineering, Planning and Land Surveying firm with the capability to assist private clients and public agencies with coordinated development services.
WILLIAM A. STEEN & ASSOCIATES was established in 1984 as a result of the retirement of several partners and the reorganization of Lawrence, Fogg, Smith & Associates. The President of the corporation is William A. Steen with Robert K. Fogg adding his 40 years of expertise to the firm.
WILLIAM A. STEEN & ASSOCIATES provides their clients a full range of civil engineering, planning and surveying services from preliminary studies, project planning, surveying and engineering design to construction staking, construction review and project management. The practice of the firm includes major design work in the fields of streets and highways, drainage, flood control water distribution and storage facilities, sewage collection systems, harbor and waterfront projects, recreational and park development, and comprehensive land planning, residential subdivisions, shopping centers and industrial park developments. The principals of the firm have also been expert witnesses on numerous litigation matters throughout the San Diego region.


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As you walk through the hand carved wooden door and into the warmly lit lounge, you hear relaxing yet uplifting jazz playing in the background. You are always greeted with a warm smile and a cup of tea or water to relax and refresh with. Most of the décor and furniture are either made from re-purposed materials that have been personally refurbished or purchased from local consignment shops.
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Thank you for your interest in our salon! Before you book, please read our cancellation policy.


The best performing GP surgeries in the Harrogate District have been revealed, following ratings by NHS choices based on whether patients would recommend the service to others.
There are some 20 GP surgeries in the district listed on the NHS choices website, which are ranked here by the percentage of those who would recommend their practice to a friend.
According to the ratings, anything below a 70 per cent average rating is considered 'among the worst', while anything with 90 per cent or above is 'among the best'.
Those rated between 70 per cent to 89 per cent are classed as 'OK'.
The survey is conducted every six months by NHS choices, and is sent to roughly 1.36 million adult patients registered at surgeries up and down the country.
In Harrogate all 20 surgeries score above 70 per cent based on their rate of recommendation.


text:
Q: [iOS][Background][CLLocationManager]Bad map accuracy I am working on an application which aims to display on a map the position of the iPhone during an activity (adding annotations and drawing line between them).
To do this, I use a Location Manager which get new positions and notify the MapDisplayViewController. When using with the simulator I got good results as you can see here http://www.youtube.com/watch?v=ESLIYSU_Mqw but with an iPhone I got weird result such 200 meters wrong.
I also use a MKMapView to display the device position. with these settings (next code block) I got that http://grab.by/mgUU.
If I show the user location I got different results, it is normal ?
- (void)setupMap {
self.mapView.delegate = self;

[self.mapView setUserTrackingMode:MKUserTrackingModeFollow animated:YES];
[self.mapView setUserInteractionEnabled:NO];

[self.mapView setShowsUserLocation:NO];
[self.mapView setZoomEnabled:NO];
[self.waitingView start];

}

Here screenshots with a real device:

*

*background: http://grab.by/mgN2

*no background: http://grab.by/mgNc
edit: the difference come froms I used for these 2 cases, 2 different ways of getting current location of the device are used:

*

*the handle from the mapView when the app is active

*the handle from the Location Manager when the app is in background

Does it a good idea to mix both locations system ?
I also test this solution CLLocationManager and accuracy issues - any experiences? but I got the same result.
Thanks ;)
Setup of Location Manager:
- (void)setup {
self.locationManager = [CLLocationManager new];
self.locationManager.delegate = self;

self.locationManager.desiredAccuracy = kCLLocationAccuracyBest;
self.isUpdatingLocation = NO;
}

Notification: when adding location in background:
- (void)doUpdateWithLocation:(CLLocation *)location {

dispatch_async(dispatch_get_global_queue(DISPATCH_QUEUE_PRIORITY_DEFAULT, 0), ^{

    [self beginBackgroundUpdateTask];

    NSLog(@"%s do update in background %@", __PRETTY_FUNCTION__, location);

    if (self.userLocationFound == NO && self.isUpdatingLocation == YES) {
        self.startCoordinate = CLLocationCoordinate2DMake(location.coordinate.latitude, location.coordinate.longitude);

        self.userLocationFound = YES;
    }
    else if (self.isUpdatingLocation) {
        static int distance;

        ABGPSPosition *position = [[ABGPSPosition alloc] init];
        position.startPoint = MKMapPointForCoordinate(self.startCoordinate);
        position.endPoint = MKMapPointForCoordinate(location.coordinate);

        //INFO: Get the distance between this new point and the previous point.
        CLLocationDistance metersApart = MKMetersBetweenMapPoints(position.startPoint, position.endPoint);
        if (metersApart > MINIMUM_DELTA_METERS) {
            MKMapPoint points[2] = {position.startPoint, position.endPoint};

            distance += metersApart;
            NSLog(@"%s - %d", __PRETTY_FUNCTION__, distance);

            NSInteger count = [self.measurementArray count];
            [self willChange:NSKeyValueChangeInsertion
             valuesAtIndexes:[NSIndexSet indexSetWithIndex:count] forKey: @"measurementArray"];
            [self.measurementArray insertObject:location atIndex:count];
            [self didChange:NSKeyValueChangeInsertion
            valuesAtIndexes:[NSIndexSet indexSetWithIndex:count] forKey: @"measurementArray"];

            self.startCoordinate = CLLocationCoordinate2DMake(location.coordinate.latitude, location.coordinate.longitude);
        }

    }

        [self endBackgroundUpdateTask];
    });
}

MapDisplayViewController get the new location:
- (void)observeValueForKeyPath:(NSString *)keyPath ofObject:(id)object change:(NSDictionary *)change context:(void *)context
{

if ([keyPath isEqualToString:keyPathMeasurementArray]) {
    if ([change[NSKeyValueChangeKindKey] intValue] == NSKeyValueChangeInsertion) {

        NSIndexSet *insertedIndexSet = change[NSKeyValueChangeIndexesKey];

        [insertedIndexSet enumerateIndexesUsingBlock:^(NSUInteger idx, BOOL *stop) {

            CLLocation *location = self.locationManager.measurementArray[idx];

            MKUserLocation *userLocation = [[MKUserLocation alloc] init];
            [userLocation setCoordinate:location.coordinate];
            NSLog(@"%s - didUpdateUserLocation", __PRETTY_FUNCTION__);

                [self.locationBackgroundList addObject:userLocation];
                NSLog(@"%s | %@", __PRETTY_FUNCTION__, self.locationBackgroundList);
        }];
    }
}
else {
    [super observeValueForKeyPath:keyPath ofObject:object change:change context:context];
}
}

MapDisplayViewController adding Annotation the new map view:
- (void)handleAddLocations {
NSLog(@"%s | %@", __PRETTY_FUNCTION__, self.locationBackgroundList);

if ([self.locationBackgroundList count] > 0) {
    for (MKUserLocation *backgroundUserLocation in self.locationBackgroundList) {

        {
            LocAnnotation* annotation = [[LocAnnotation alloc] initWithCoordinate:backgroundUserLocation.coordinate];
            NSLog(@"%s %@", __PRETTY_FUNCTION__, [backgroundUserLocation description]);

            [self.mapView addAnnotation:annotation];
        }
        [self mapView:self.mapView didUpdateUserLocation:backgroundUserLocation];
    }

    NSString *message = [NSString stringWithFormat:@"%s | Annotation number: %d", __PRETTY_FUNCTION__, [self.locationBackgroundList count]];
    UIAlertView *alert = [[UIAlertView alloc] initWithTitle:@"Debug" message:message delegate:self cancelButtonTitle:@"Cancel" otherButtonTitles:@"OK", nil];
    [alert show];

    [self.locationBackgroundList removeAllObjects];
    self.locationBackgroundList = [[NSMutableArray alloc] init];
    }
}

A: Fixed you have to use only one way to locate your device with the CLLocationManager or the MapView. ;)

redpajama_set_name: RedPajamaStackExchange


text:
Q: Mode in which system programs are executed I think that i get what system programs are, but i would like to understand why exactly they are executed partly in User mode and partly in Kernel mode.
Since computer software designed to provide services to other software, i thought that they may run entirely in kernel mode. In what casses they run in user mode?

A: the kernel mode and user mode level exists to prevent user software from damaging the system and its features.
how the user mode performs low level instructions?
ans - using system calls
a user-mode program can switch into kernel mode,but have no control over the instructions which will be performed in kernel mode.
so the only way this could happen is using system call, which interface used by User Mode to talk with low level resources (hardware).
The only exception is when a process uses ''ioperm'' system call. In this case a device can be accessed directly by
User Mode process (IRQs cannot be used).
during the process ,
The user-mode program places values in registers, or creates a stack frame with arguments,
to indicate what specific service it requires from the operating system. then performs the trap instruction.
Immediately, the CPU switches to kernel mode, and jumps to instructions at a fixed location in memory.
trap instruction or system call handler, read the details of the requested service + arguments, and then
perform this request in kernel mode.
finally With the system call done, the operating system resets the mode
to user-mode and returns from the system call.


text:
Goniobranchus collingwoodi () è un mollusco nudibranchio della famiglia Chromodorididae.

Distribuzione e habitat
La specie è diffusa nell'Oceano Pacifico.

Note

Bibliografia

Altri progetti

Collegamenti esterni

Chromodorididae


text:
'use strict';

var WorldData   = require('../../Common/src/API/Data/WorldData.js');
var ZoneData    = require('../../Common/src/API/Data/ZoneData.js');
var FactionData = require('../../Common/src/API/Data/FactionData.js');
var LoadoutData = require('../../Common/src/API/Data/LoadoutData.js');

var initializeCallback;

// Don't use {}
var worlds   = Object.create(null);
var zones    = Object.create(null);
var loadouts = Object.create(null);
var factions = FactionData;

var ReferenceData = {
    startFetchData: function(callback) {
        WorldData.startFetchWorlds(function (worldDictionary) {
            worlds = worldDictionary;
            if (isDataLoaded()) {
                callback();
            }
        });
        ZoneData.startFetchZoneData(function(zoneDictionary) {
            zones = zoneDictionary;
            if (isDataLoaded()) {
                callback();
            }
        });
        LoadoutData.startFetchLoadouts(function(loadoutDictionary) {
            loadouts = loadoutDictionary;
            if(isDataLoaded()) {
                callback();
            }
        });

        initializeCallback = callback;
    },
    getWorlds() {
        var worldArray = [];
        for (var worldId in worlds) {
            worldArray.push(worlds[worldId]);
        }
        return worldArray;
    },
    lookupWorld: function(worldId) {
        return worlds[worldId];
    },
    lookupZone: function(zoneId) {
        return zones[zoneId];
    }
};

function isDataLoaded() {
    if (worlds && zones && factions && loadouts) {
        return true;
    } else return false;
}

module.exports = ReferenceData;


Hit the streets of Cairo with Eugene and Alex as Genre Cult looks into Mahraganat. Auto-Tuned Arabic gangsta rap with a comedic flair. This music has been becoming more and more popular in Egypt over the last few years. Listen as the boys fumble over pronunciations and lack of understanding the Arabic lyrical content, but also talk to Mahraganat producer and MC Michael from Tamer + Michael (with some Skype gremlins messing up the quality a little).


text:
ACT Presents "THE NERD"
Friday, Oct 01, 2021 8:00p -
https://go.evvnt.com/887207-0?pid=5248 Attleboro Community Theatre
Attleboro, Massachusetts 02703
https://go.evvnt.com/887207-0?pid=5248
Willum Cubbert, an aspiring young architect in Terre Haute, Indiana, has often told his friends about the debt he owes to Rick Steadman, a fellow ex-GI whom he has never met but who saved his life after he was seriously wounded in Vietnam. He has written to Rick to say that, as long as he is alive, "you will have somebody on Earth who will do anything for you"-so Willum is delighted when Rick shows up unexpectedly at his apartment on the night of his thirty-fourth birthday party. But his delight soon fades as it becomes apparent that Rick is a hopeless "nerd"-a bumbling oaf with no social sense, little intelligence and less tact-whose continued presence among Willum and his friends leads to one uproarious incident after another.
Facebook: https://go.evvnt.com/887207-2?pid=5248
01/10/2021 20:00:00 17/10/2021 22:30:00 15 ACT Presents "THE NERD" Willum Cubbert, an aspiring young architect in Terre Haute, Indiana, has often told his friends about the debt he owes to Rick Steadman, a fellow ex-GI whom he has never met but who saved his life ... Attleboro Community Theatre, Attleboro, Massachusetts 02703 Organizer Organizer e-mail false DD/MM/YYYY Reddit


text:
Kenya cabinet approves constitutional transition funds
Friday 29 October 2010 at 8:05 AM ET
by Daniel Makosky
The Kenyan Cabinet [official website] on Thursday authorized [press release] a 3.5 billion shilling expenditure to finance the transition to the country's new constitution. The funds, roughly USD $43 million [Reuters report], are intended to facilitate implementation of the revised charter by the close of the current fiscal year. The new constitution includes numerous checks on presidential authority [JURIST report], among which are the creation of a supreme court and senate.The constitution also requires reforms [Guardian report] to the nation's judiciary and land tenure system and improvements in civil rights and women's representation. The document has been received as one of the most significant events in Kenya since its independence, and its implementation was originally thought to require as long as five years.
Kenyan President Mwai Kibaki [official profile] signed the new constitution into law in August, weeks after it was approved [JURIST report] by popular referendum. The document's creation was part of a power-sharing agreement [JURIST report] reached in 2009 between Kibaki and opposition leader Prime Minister Raila Odinga [official website] that brought an end to the civil unrest that followed the contested 2007 presidential election [JURIST report]. Election officials sought to make the referendum as inclusive and peaceful as possible by allowing prisoners to vote and prosecuting those who suggested violence in reaction to the changes [JURIST reports] under hate speech laws.
constitutions international Kenya


text:
Q: Reading specific key values from a dictionary of dictionary I have a dictionary of dictionaries as follows:
dictofdict = {'001': {'date': 201504, 'status':'New'}, '002': {'date':201504, 'status':'Constant', 'rate':'-10'}, '003':{'date': 201504, 'status':'In Review'}}

The inner dictionaries may or may not have all the following keys: date, status and rate. For example: 001 and 003 do not have the key rate in their dictionary of values.
How do I read this dictionary of dictionaries such that I have an output as follows. I am interested in only the date and status keys from the inner dictionaries.
201504    001    New
201504    002    Constant
201504    003    In Review

A: You can use an if clause to check if they exist in the inner dictionary
>>> for k,v in dictofdict.items():
...      if 'date' in v and 'status' in v:
...           print("{}\t{}\t{}".format(v['date'],k,v['status']))
...
201504  003 In Review
201504  002 Constant
201504  001 New

If you are particular about the order then you will have to use sorted as a dictionary otherwise is un-ordered
>>> for k,v in sorted(dictofdict.items()):
...      if 'date' in v and 'status' in v:
...           print("{}\t{}\t{}".format(v['date'],k,v['status']))
...
201504  001 New
201504  002 Constant
201504  003 In Review

As Padraic mentions you can use a list comprehension to store these values.
[(k, d["date"], d["status"]) for k, d in sorted(dictofdict.items()) if "date" in d and "status" in d]

This can be used as
>>> l = [(k, d["date"], d["status"]) for k, d in sorted(dictofdict.items()) if "date" in d and "status" in d]
>>> for i,j,k in l:
...     print("{}\t{}\t{}".format(i,j,k))
...
201504  001 New
201504  002 Constant
201504  003 In Review

As JonCle mentions below
You can use set.issubset in your clause too.
This can be used as
>>> for k,v in sorted(dictofdict.items()):
...       if {'date', 'status'}.issubset(v):
...            print("{}\t{}\t{}".format(v['date'],k,v['status']))
...
201504  001 New
201504  002 Constant
201504  003 In Review

One final approach is the EAFP. Called as Easier to ask for forgiveness than permission, you can avoid the if clause completely here!
>>> for k, v in sorted(dictofdict.items()):
...     try:
...         print '{date}\t{}\t{status}'.format(k, **v)
...     except KeyError:
...         pass
...
201504  001 New
201504  002 Constant
201504  003 In Review

The working of this is that we assume that the key is present in the dict. If it is not there, an exception would be raised. Here we choose to ignore that as it is not required for us.
Note:
As you have a dictionary here, you can take advantage of the format method here to print the keys of the dictionary (You can see a few examples here) and supply the keys of the dictionary as fields in format
This can be done as
print('{date}\t{}\t{status}'.format(k, **v))

A: To do this, you need to check if inner dicts contain the key status and date. Also, to print in order, you can use the sorted() function.
>>> dictofdict = {'001': {'date': 201504, 'status':'New'}, '002': {'date':201504, 'status':'Constant', 'rate':-10}, '003':{'date': 201504, 'status':'In Review'}}

>>> for number in  sorted(dictofdict):
    # Only print if date and status key are present in the inner dict
    if 'date' in dictofdict[number] and 'status' in  dictofdict[number]:
        print '{}\t{}\t{}'.format(dictofdict[number]['date'], number, dictofdict[number]['status'])

201504  001 New
201504  002 Constant
201504  003 In Review


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