Op-ed: What would the Brexit mean for Science and Research?
As the date of the referendum, June the 23rd, rapidly approaches, both the "Leave" and "Remain" campaigns are publishing increasingly aggressive headlines in an attempt to sway the 10% of voters who remain undecided about whether the United Kingdom should stay in or leave the European Union . The Leave campaign is aiming to persuade voters that the UK needs to "regain control" and "end the supremacy of EU law" saying that a vote to leave "is much safer than giving Brussels more power and money every year." . They argue that the UK sends £350 million every week to the EU and that it would be better if this money was spent on the UK. The Remain campaign, on the other hand, argues that EU countries invest £66 million in the UK every day, that for every £1 the UK puts into the EU we get almost £10 back in the form of jobs, trade, investment and lower prices . In fact, both campaigns have been confusing the general public with conflicting claims resulting from different assumptions made when analysing data, for example in the claims that "The EU costs the average UK household as much as £9,265 a year." (Leave campaign) and that ".. all the trade, investment, jobs and lower prices that come from our economic partnership with Europe is worth £3,000 per year to every household." (Remain campaign) . It is no wonder that voters are unsure as to what the real effects of a Brexit would be. One of the many questions that remain is: What would happen to Science and Research, both in the UK and in Europe, as a result of a Brexit?
Unfortunately, the answer to this question is not known. This is, in a very large part, because there is no certainty as to what would happen to the UK budget upon leaving the EU and what the relationship of the UK with the EU will be . Nor is it clear, how the UK would change its immigration policy and whether there would be exemptions for researchers, as was the case with the new immigration rules enacted on the 6th of April this year . Much of the Leave campaign's rhetoric has related to immigration  and therefore it is likely that if the UK was to vote to leave the EU, new immigration controls would be put into place. Exactly what these changes would be has not been outlined by the Leave campaign.
We do know a few things, however, thanks to the Science and Technology Committee's report published in April 2016 , and the UNESCO science report "Towards 2030" published in November 2015 . The latter concludes that a Brexit would have far-reaching consequences not only for British science, but also for European science. I will describe a few of the key points mentioned in these reports below.
The European Union is a very important centre of science worldwide, currently producing over one third of the world's scientific output according to UNESCO data . This can be partly attributed to the fact that 8% of the EU budget goes directly into Horizon 2020, the current EU framework programme for research and innovation, worth just under €80 billion from 2014 – 2020 . This money is accessible to anyone within the EU, from students to established professors. Through Horizon 2020, individual researchers and groups in the UK can collaborate with researchers in over 170 countries worldwide , fuelling high-quality collaborative research . However, this money may not become entirely inaccessible to the UK if it is no longer an EU member state, as there are several countries which currently are eligible to receive funding through Horizon 2020 as Associated Countries. If this were to become the case, it is probable that the level of influence the UK would be allowed to maintain regarding science policy decision making would decline  as well as the funding available to the UK , despite it still being expected to make a significant financial contribution to the EU.
Within the scientific community, the message is clear. In a recent poll of scientists conducted by the journal Nature, of the respondents who intended to vote in the referendum, 80% said that they would vote to remain in the EU, and 78% said that a Brexit would harm UK science (while 9% said that it would benefit) . Additionally, a group of 13 Nobel laureates recently wrote an open letter to the Telegraph newspaper, stating their support for the Remain campaign, as they believe that leaving the EU poses a "key risk" to UK science . They argue that "Science thrives on permeability of ideas and people, and flourishes in environments that pool intelligence, minimise barriers, and are open to free exchange and collaboration. The EU provides such an environment and scientists value it highly." .
Regardless of the decision made on June the 23rd, it is likely that the UK will have lost some of its welcoming appeal to international researchers as a result of the anti-EU and anti-immigrant rhetoric that has been filling many of headlines over the past months. The very uncertainty of what would happen if the UK were to leave the EU is likely to be damaging to the UK economy, meaning that any estimates of savings made by leaving are likely to be inaccurate. There is no precedent for what would happen if a country was to leave the EU, therefore it is difficult to predict the relationship that the EU would have with the UK. However it is likely that, in order to dissuade other countries from pulling out, the conditions offered would be less than favourable. Whether this would be damaging to science and research remains to be seen.
Katarzyna Tych, Lindau Alumna 2016, is a Human Frontiers research fellow, from the UK, at the Technical University of Munich in Germany. She is performing research at the interface of physics and biology. Her work centres on developing advanced physical experimental techniques to study the functions of proteins on the single-molecule level.


All BC Secondary school students who are enrolled in Grade 10, 11 or 12 must complete Graduation Transitions.
Students are responsible for planning and preparing their education, career and life goals through Graduation Transitions. Schools are responsible for ensuring that students have opportunities to meet the Prescribed Learning Outcomes. Teachers are responsible for assessing and providing feedback to students. For detailed information on Graduation Transitions refer to the Program Guide.


The 200m² villa is decorated with stylish modern furniture, consists of one floor and is set in an amazing garden with panoramic views. It features an open plan kitchen-dining-living area with large windows leading to the furnished terrace and swimming pool area with panoramic views.
The living area features a comfortable corner sofa, a coffee table, a fireplace, A/C, floor heating and a Smart TV and a large window with amazing view. The dining table seats 6 persons (2 chairs can be added).
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The corridor leads to the 4 bedrooms and bathrooms.
The master bedroom has a king size bed, Smart TV, en suite bathroom with Jacuzzi bath (aero- & hydromassage) and a terrace with view to the garden and lazy river.
The double room features a queen size bed and balcony. The twin bedroom features a Smart TV and the single bedroom features an office desk (should you need some time for your emails), a Smart TV and a balcony. A comfortable folder bed can be added into the single bedroom for the 8th person.
3 bedrooms share the bathroom with shower. The bathroom features a washing machine and dryer.
All rooms with A/C and floor heating. There are no steps inside the house.
The outside area is unique and will make any guest not wanting to leave the property.
The Gazebo is fully equipped with comfortable lounge furniture, kitchenette with fridge and a Smart TV. The children can safely float in the lazy river while you are enjoying a cool beer or a glass of Prosecco and enjoy the amazing view. The sound of the waterfall soothes your brain and soul! Or the ladies enjoy relaxation at its fulliest with a cool cocktail sitting in the Jacuzzi, while the men enjoy watching the Mondial 2018 or any Sports event in the Gazebo!
The terrace is furnished with a table and 6 chairs (2 chairs can be added), a mobile BBQ and overlooking the Cretan Sea and the olive groves. It leads into the garden to the biological salt water pool (45m²) with 3 built in sun loungers and stylish sunbeds, the separated children pool, the lazy river with the waterfall and the Jacuzzi (aero- & hydromassage) for 8 persons.
The villa with garden is secluded and features private parking.
Guests have access to all the villa and garden, as per our description.
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Car hire is recommended and we can give you information about that.
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Democracy and state of the nation (2)
Home/Rise Networks Community, Youth Speak, YOUTH SPEAK ON THE GUARDIAN/Democracy and state of the nation (2)
(By Ezeugwu Austin Ifeanyi)
"The argument that democracy is the system best suited for resolving conflicts on the basis of consent in a complex modern society is true only up to a point. The universalism and formality that characterise the rule of law in democratic societies do provide a level playing ground on which people can compete, form coalitions and ultimately make compromises. But it is not necessarily the case that democracy is the political system most capable of resolving social conflicts per se."
Continued from Friday, 20-6-2014
BEFORE the dawn of democracy in Nigeria, the country was characterised by persistent religious bigotry and ethnic rivalry, mercantilist economic policies, a pervading sense of injustice in the social structure and marginalisation. So by the time democracy set in, it marked enormous disparities in wealth, prestige, status and power which the microscopic few use to control the democratic process. The social pathology that followed was inevitable; the dominance of a cabal that necessitated an equally intransigent opposition. It is not a gainsaying that man has a natural desire for struggle no matter what the stakes are.
Experience had shown us that there are people for whom the success of a government does not mean the satisfaction of their amour proper (self love). Such people cannot imagine living in a world without struggle. If they cannot fight on behalf of a just cause, they will fight against the just cause. And if the greater part of the world in which they live is characterised by peaceful and prosperous government, then they will struggle against that peace and prosperity, against that government. They will struggle for the sake of struggle. The common denominator here is that the success and stability of a government never depends simply on the mechanical application of a certain set of universal principles and laws, but requires a degree of conformity between peoples and states.
The argument that democracy is the system best suited for resolving conflicts on the basis of consent in a complex modern society is true only up to a point. The universalism and formality that characterise the rule of law in democratic societies do provide a level playing ground on which people can compete, form coalitions and ultimately make compromises. But it is not necessarily the case that democracy is the political system most capable of resolving social conflicts per se. A democracy's ability to peacefully resolve conflicts is greatest when those conflicts arise between interest groups that share a larger, pre-existing consensus on the basic values or rules of the game, and when the conflicts are primarily economic in nature. Cases abound in the country of such disputes that were promptly put to rest through democratic means. But there are other kinds of non-economic conflicts that are far more intractable, having to do with issues like inherited social status and nationality, ethnic loyalties and religious fundamentalism which democracy is not primarily good or even geared at resolving.
Even American democracy, as stable as it seems, has not been particularly successful in solving its most persistent ethnic problem, precisely that of American blacks. Black slavery constituted the major exception to the generalisation that Americans were born equal. In fact, American democracy could not settle the question of slavery through democratic means. Years after the achievement of full legal equality by American blacks, many remain profoundly alienated from the mainstream of American culture. (One difference though is that none of the American ethnic groups constitutes a nationality, living in their own land and speaking their own language).
Nigeria is highly polarised along lines of social class, ethnicity, and religion, and democracy is not satisfactorily functional under such situation. If the military, with its monopoly of power, had stemmed the tide of religious and ethnic violence while it held sway, thereby creating the spirit of tolerance and equality in the socio-political life of the people, the country would have been better for it. A modernising military government can in principle be far more effective than a democracy in creating the social conditions that would permit rapid economic growth, and over time, the emergence of a successful democracy. The major aim of the military junta that took over power in Argentina from President Isabella Peron in 1976 was to rid Argentine society of terrorism and forces that threatened the nation's sovereignty.
The question of national sovereignty is inherently uncompromisable. Little wonder President Goodluck Jonathan categorised it as a 'no-go area' in the ongoing national conference. Fortunately or unfortunately, realities on ground have made that position untenable. Sovereignty either belongs to a people or the other. For example, the Soviet Union could not become democratic and at the same time remain unitary, for there was no consensus among the Soviet Union's nationalities that they share a common citizenship or identity. Democracy could only emerge on the basis of the country's break up into smaller national entities. When different groups that constitute historical communities living on their traditional lands and speaking their own language, with a memory of past nationhood and sovereignty come into conflict, there is seldom a way of splitting the difference through peaceful democratic means, as there is in the case of economic disputes.
If we are to tell ourselves the truth, Nigeria carries a burden too heavy for democracy. And until we lighten this burden, genuine dividends of democracy –peace and prosperity- will continue to elude us, the sovereignty of Nigeria will, more often than not, be threatened, and the labour of our heroes past, in vain. As the marriage between one Nigeria and democracy continues to suffer asunder, let us note that it is either one Nigeria or democracy, not the two (at least for now). They are incompatible and it is high time we realised that. It was in the struggle to break the grip of colonialism that we learnt the need for unity. There is even a greater need for understanding now that we seek to correct the mistake of 1914. Members of national conference, please take note!
Concluded.
Ifeanyi, a political analyst wrote via austinehippo@gmail.com 08035014819
The YOUTHSPEAK Column which is published daily, on weekdays, on the back cover of THE GUARDIAN Newspaper, is powered by RISE NETWORKS, Nigeria's Leading Youth and Education Development Social Enterprise, as a substantial advocacy platform available for ALL Nigerian Youth to engage Leadership at all levels, engage Society and contribute to National Discourse on diverse issues especially those that are peculiar to Nigeria.
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By RISE NETWORKS|2014-06-23T09:18:59+01:00June 23, 2014|Rise Networks Community, Youth Speak, YOUTH SPEAK ON THE GUARDIAN|0 Comments

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Become A SAGC Pass Holder!
The Audubon Cooperative Sanctuary Program is an environmental education and certification program that helps golf courses protect the environment while preserving the natural heritage of the game of golf. Through collaborative efforts (which began in 1991 with the United States Golf Association), membership in the ACSP has steadily grown to include more than 2,300 golf courses in the United States and three dozen countries worldwide.
We proudly received our Audubon Program Certification on May 30th, 2014.


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What is DepositBook.com?
Who are the key staff?
Who are the stakeholders in the journey?
What do we solve ?
How does the transaction take place?
What are the different type of products available on the Platform?
What are the different type of services?
What is the cost for using the Platform?
Key staff include:
Mr. Siddharth Bhandari, CEO
Mr. Vikram Kelkar, COO
Mr Amit Gupta, CTO Consultant
Mr Arun Aggarwal, CEO DepositBook UK.
Details of key staff:
Mr. Siddharth Bhandari - is the former Managin Director at Societe Generale Asset Management. He has a Masters in Finance from the London School of Economics
Mr. Vikram Kelkar - is the former Regional Head of Business Management and Client Management for HSBC, Middle East. He is a Chartered Accountant and a Certified Cash Manager (ACT, UK)
Mr. Arun Aggarwal - is a former partner at PwC and Managing Director of SWIFT for the UK, Ireland and Nordics. He is a Chartered Accountant and member of the Association of Corporate Treasurers, UK.
Mr. Amit Gupta - is a Consultant CTO with vast experience in the development of Technology functions in starups (with a focus on Fintechs) and new technologies. He is a MBA by qualification.


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Nick Austin
Last Modified: April 1, 2021
Born Name : Nick Austin
Nicknames : Nick
Birth Sign : Cancer
Occupation : Social Media Star
Birthplace : San Diego, California, United States
Location : San Diego, California, United States
Skin Type : Fit
Body type : Mesomorph
Net Worth : $1 million – $1.5 million
Hair Length : Medium
Hair Color : Brown
Instagram : https://www.instagram.com/nickaustin
Twitter : https://twitter.com/nickkaustin
Tiktok : https://www.tiktok.com/@nickaustinn
Youtube Channel : https://www.youtube.com/c/NickAustin
Nick Austin Facts
Lip sync and dance content creator who rose to fame by sharing short form videos on his nickaustinn TikTok account. He has built a fanbase of more than 9 million followers on the platform
Nick Austin was born on July 1, 2000, in San Diego, California, USA. He holds the American nationality and belongs to White ethnicity.
His Zodiac sign is Cancer.
His mother's name is Jo Anne Taylor who works as a production assistant for the mortgage company "The Kolesar Team". His family is the native people of San Diego, California.
He was grown up in his home town San Diego by his parents and attended the local High school. He is a follower of Christianity (religion).
He is a member of the TikTok group The Hype House alongside Thomas Petrou, Addison Rae and Alex Warren amongst others.
He was handcuffed to Chase Hudson for a May 2020 TikTok dance video that earned over 2 million views.
He Rickrolled his friends in a viral 2019 TikTok video.
He was a ring boy when his parents got married.
His first kiss happened the same day when he kissed the flower girl.
One of his fans fainted after seeing him in person.
YouTube Channel (569k subscribers)
Instagram (3.6 million followers)
Twitter (1.4Mn followers)


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Home | FeelWell | Be Smart About Antibiotic Use
Cold & Flu Season
Be Smart About Antibiotic Use
Runny nose. Earache. Scratchy throat. It's cold and flu season, and lots of people will experience these symptoms.
Before you run to the doctor hoping to get a prescription for an antibiotic to lessen the symptoms, consider this fact: Antibiotics are not effective against viral infections like common ailments like the cold, bronchitis and ear infections.
"More than half of antibiotics prescribed for patients in the United States are inappropriately prescribed," says Allison Weinmann, M.D., an infectious diseases physician at Henry Ford Hospital who is leading Henry Ford's antimicrobial stewardship program. "Antibiotics are not helpful for treating viruses like the cold, flu and upper respiratory infections. Taking them for a virus may be harmful."
According to the Centers for Disease Control and Prevention, one out of five emergency department visits for adverse drug events are due to antibiotics. They're also the most common cause of emergency department visits for adverse drug events in children under 18.
Dr. Weinmann says consider these tips for alleviating symptoms of viral infections:
Get plenty of rest.
Use a humidifier or cool mist vaporizer to help with respiratory symptoms.
Use saline nasal spray or drops.
Gargle with salt water for a sore throat.
For an earache, put a warm moist cloth over the ear that hurts.
Antibiotic overuse has led to a serious health problem called antibiotic resistance, in which bacteria don't kill germs and the germs survive and continue to multiply, rendering medications less effective at curing or preventing infections.
Dr. Weinmann says everyone can do their part to help curb antibiotic resistance:
If prescribed an antibiotic, take it exactly as prescribed by your doctor.
Never skip a dose and take the medicine until gone, unless directed otherwise by your doctor.
Get vaccinated. Vaccination prevents many illnesses treated with antibiotics.
Wash your hands frequently throughout the day, year-round.
Stay home from work or school if sick.
Antibiotic resistance in humans is also linked to the farm industry in which researchers found that cattle raised with antibiotics to promote growth and reduce disease are more likely to carry drug-resistant bacteria than from cattle that received no antibiotics. That drug-resistant bacteria is likely to be ingested by humans when they consume those meats and poultry, says Dr. Weinmann.
"I would caution consumers to look for meats and poultry that contain no antibiotics. You may pay a little more, but your dollars count towards banning routine antibiotic administration in farm animals solely for growth purposes. Additionally, it may reduce your risk of acquiring an antibiotic resistant germ," Dr. Weinmann says.
To schedule an appointment with a doctor when you're sick, call 1-800-HenryFord (436-7936) or visit henryford.com. Don't have a primary care provider? Find one today.
Dr. Allison Weinmann specializes in infectious diseases and sees patients at Henry Ford Hospital.
Tags:Dr. Allison Weinmann,infectious disease,primary care


The integration of processes shown in the Venn diagram below is critical for an individual to be a proficient learner. The acquisition of knowledge, upon which educational standards are determined, is predicated on the underlying processes of human learning.
The ability to process language is a prerequisite to learning content. Specifically the ability to decode, the ability to retain sight words, the ability to spell, the ability to comprehend written and oral language, and the ability to think critically are all necessary for success in content areas.
It is the goal of the Lindamood-Bell program to develop these abilities to a point that our students become independent and self-correcting.
Students can successfully learn content when they can read and comprehend efficiently.
Simply put, the goal of learning to read is to get meaning. Underlying these steps are the sensory-cognitive factors and their component parts.


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Interview: Leslye Headland Crashes the Party with "Bachelorette"
The delightfully outspoken writer/director discusses the love of movies (and the ex-boyfriends) that led her into filmmaking, her debauched debut film about a bridesmaids' party gone awry and why we don't want to return to the '90s.
Burning Bargain
Burning Bargain: "Party Down" Seasons 1 & 2 for $9 on Amazon; "It's the Garry Shandling Show: The Complete Series" for $54
I'm not even certain "Party Down" is my favorite show from Rob Thomas, the TV mastermind behind "Veronica Mars" and "Cupid," but it's undoubtedly one of the best depictions of the underbelly of show business committed to screen in addition to being really, really goddamn funny. If a cast that includes Adam Scott, Lizzy Caplan, Jane Lynch, Ken Marino, and Martin Starr as a group of disgruntled caterers doesn't get you excited, then this oral history of what made the show so great will have to do. But then again, if you're still reading this, you're probably already a fan of the show. So it is more than a pleasant surprise that both seasons of the short-lived show have dropped to $8.99 on Amazon, which is considerably less than their $30 retail tag or their $2 an episode rate on most digital delivery systems. Here's the links for Season 1 and Season 2.


The Brazilian Society of Cardiology (SBC) proposes that hypertensive subjects who use beta-blockers and practice physical exercises must have their training heart rate (HR) corrected due to the negative chronotropic effect of this drug. Nevertheless, if the physical activity is performed outside of plasmatic half-life, correction may not be necessary. This study investigated the exercise chronotropic response both inside and outside the beta-blocker plasmatic half-life. Nine subjects in use of atenolol or propranolol, and six controls, carried out three walking sessions in three days according to different schedules: EX2 (two hours after drug administration, at the plasmatic peak); EX11 (eleven hours after drug administration, at the end of plasmatic half-life); and EX23 (twenty-three hours after drug administration, outside the plasmatic half-life. The walking sessions were performed on an ergometric treadmill and HR was monitored by a heart rate monitor. During the exercises, mean HRs were 97.2, 108.4 and 109 for EX2, EX11 and EX23, respectively, with the value for EX2 statistically lower than the others (p<0.05). There were no statistical differences in the control group (p>0.05). The study concludes that the attenuation of the positive chronotropic response which occurs during exercise in subjects using beta-blockers, is less evident when the exercise is performed outside the plasmatic half-life of the drug.
Uniterms: Beta-blockers/negative chronotropic effect. Atenolol. Propanolol. Hypertension. Physical exercise. Training heart rate/control.
A Sociedade Brasileira de Cardiologia (SBC) propõe que os hipertensos que utilizam beta-bloqueadores e praticam exercícios físicos devem ter sua frequência cardíaca de treinamento (HR) corrigida devido ao efeito cronotrópico negativo desse fármaco. Contudo, se a atividade física é realizada fora da meia-vida plasmática do fármaco, a correção pode não ser necessária. Este estudo investigou a resposta cronotrópica ao exercício dentro e fora da meia-vida plasmática do beta-bloqueador. Nove indivíduos que usavam atenolol ou propranolol e seis controles, efetuaram três sessões de caminhada em três dias, de acordo com diferentes esquemas: EX2 (duas horas após a administração do fármaco, no pico plasmático); EX11 (11 horas após a administração do fármaco, no fim da meia-vida plasmática) e EX23 (23 horas após a administração do fármaco, fora da meia-vida plasmática). As caminhadas foram realizadas em esteira ergométrica e a HR foi monitorada por monitor de freqüência cardíaca. Durante os exercícios, as HR médias foram de 97,2, 108,4 e 109, para EX2, EX11 e EX23, respectivamente, com valor de EX2 estatisticamente mais baixo do que os outros (p<0,05). Não houve diferenças estatísticas no grupo controle (p>0,05). O estudo conclui que a atenuação da resposta cronotrópica positiva, que ocorre durante o exercício em indivíduos que utilizam beta-bloqueadores, é menos evidente quando o exercício é realizado fora da meia-vida plasmática do fármaco.
Unitermos: Beta-bloqueadores/efeito cronotrópico negativo. Atenolol. Propranolol. Hipertensão. Exercício Físico. Freqüência cardíaca de treinamento/controle.
The practice of regular physical activity is an important tool in the prevention and non-pharmacological treatment of hypertension. Physical activity prescription must be done with caution, especially when the patient has other concomitant morbidities such as angina and heart failure. In addition to these patients being more sensitive to cardiovascular changes during their workout, they may present reduced physical performance (Baster, Basterbroks, 2005; Suzuki, Ohta, 2008; Thompson, 2004).
An important aspect that must be considered in physical exercise prescription is the relationship between effectiveness and safety, with intensity being one of the main variables involved in assuring this balance. Intensities that are too low render the exercise ineffective, since it does not trigger the cardiovascular adaptations that improve the subject's health. If the intensity is very high however, there is an increase in the risk of cardiovascular accidents during the exercise (Nelson et al., 2007; Nóbrega et al., 1999).
Heart rate monitoring is the most common method for supervision of exercise intensity. The efficacy and safety of aerobic exercise is guaranteed while training with a heart rate of between 60 and 85% of maximal reserve heart rate. This rate is called the target-zone (SBC, 2006).
However, some factors may change the heart rate. Beta-blockers (BB) are substances that inhibit the β-adrenergic receptors, promoting a negative chronotropic action, observed at rest and during exercise. This is characterized by a lower heart rate for the same effort intensity, in comparison to a situation of drug abstinence (Koshucharova et al., 2001). These drugs are divided into three categories: non-selective beta-blockers called first-generation BBs which block receptors from the subtypes called β1 and β2-adrenergic; second-generation BBs, which have selective action on the β1 receptor; and third-generation BBs that, besides β-adrenergic blockade, have a vessel expanding action (Pereira-Barreto, 2004; Firmida, Mesquita, 2001; Pedersen, Cockcroft, 2007).
Due to the slower increase of heart rate during exercise, the Brazilian Society of Cardiology (1997) suggests the use of an equation to correct heart rate values when using this variable to monitor exercise intensity. Another recommended method in physical exercise prescription to these patients is training heart rate determination through the ergometer test while under the effect of BB (Vanzelli et al., 2005).
Nevertheless, neither the correction equation suggested by the SBC nor the ergometer test under the effect of BB consider absorption time, plasmatic half-life, or substance elimination time. Likewise, they do not consider the time elapsed between administration of the BB and the time that the hypertensive subject performs physical exercise. The negative chronotropic effect magnitude may vary throughout the day once its concentration peak is obtained (approximately one hour after drug ingestion), according to the BB pharmacokinetic. In addition, the plasmatic half-life varies from one to six hours (Couto, 1998). However, depending on when the subject performs the physical exercise, its prescription with either equation use or the ergometer test under the BB effect might be misleading.
Considering these factors, this study tested the hypothesis that the negative chronotropic effects of atenolol and propranolol at rest, as well as the attenuation of the positive chronotropic effect of the exercise promoted by these drugs, vary after administration, according to the pharmacodynamics. In this sense, the present study can contribute with important information to the establishment of an ideal and safe heart rate zones for hypertensive patients, as well as pave the way for new studies, given that few studies have investigated the implications of beta-blocker use in physical exercise prescription.
This study project was submitted to the Ethics Committee of the Health Science Center of the Federal University of Paraíba, and was approved under the 1200/07 Protocol. The subjects were selected, intentionally, at the locations where they practiced walking. After an explanation of the research objectives and procedures, those who agreed to participate were asked to sign a written informed consent form.
Nine hypertensive subjects were selected, including seven females, with mean age of 53.9 years (± 2.8), and without renal dysfunction history. Participants had to be physically active and practicing aerobic exercises for at least three months, on a weekly basis, for three to five days a week. They were required to use an adrenergic beta-blocker drug in one daily dose, and administer the drug only in the first hours of the morning. Seven out of nine subjects used atenolol, and two used propranolol at doses of 25, 40 and 50 mg.
The control group comprised six hypertensive women, not in use of BB, with a mean age of 57.4 years (± 5.5), who were physically active and fulfilled to the same criteria as the experimental group regarding the way they exercised. Three subjects used alpha central agonist, two used an inhibition agent of angiotensine conversion enzyme, and one used an antagonist of AT1 receptors. After signing the informed consent form, their dates and times of walking were registered. To standardize data collection time points, all subjects were asked to administer the drug at seven o'clock in the morning. This time was confirmed by the subjects' declaration for each day in which data were collected.
Each subject carried out three walking sessions of forty minutes in duration on alternate days. Three different times were adopted for each day, considering both the time of plasmatic half-life of the beta-blocker drug and the point of maximum plasmatic concentration peak. Beta-blocker plasmatic half-life is, on average, six hours with a concentration peak of about two hours. Considering that the subjects took the drug at 7:00 a.m., the exercise was practiced two hours (EX2), eleven hours (EX11) and twenty-three (EX23) after drug administration. The same procedure was used for the control group, as was the order in which the exercises were performed.
Before and immediately after each exercise session, the blood pressure of each subject was measured by the auscultatory method, following the protocol recommended by the SBC (2006). The first session conducted was at the EX2 point. The subjects carried out a walking exercise on a Proaction treadmill, with a minimum velocity control of 0.1 km/h and a maximum velocity of 16 km/h. The exercise duration was forty minutes, with an intensity of between 60 to 80% of the maximal reserve heart rate. A period of five minutes was adopted in order to allow the treadmill velocity to reach a heart rate compliant with the determined intensity, after which a chronometer was used to register the forty minutes of exercise. The treadmill velocity in which the heart rate stabilized itself in a training zone was registered.
For the EX11 and EX23 sessions, the intensity determined was the same velocity obtained in the EX2 session. This procedure was adopted to guarantee that the subjects would do the three sessions with uniform effort intensity, in such a way as to permit study of possible heart rate changes in response to BB administration.
During each of the three exercise sessions, the heart rate was measured every two minutes, using an Oregon Scientific heart rate monitor with one beat per minute precision.
The exercise sessions were conducted in a controlled environment, with temperature of 25 ºC, measured by a West Germany thermometer, at a relative air humidity of 75%, as registered by a G. Huger hygrometer.
The subjects were asked not to do any additional physical exercise during this study data collection phase. Moreover, the subjects were asked to take their medication as normal on the days between sessions. For the EX23 session, the subjects were requested to bring their medicines to the research site, in order to guarantee that it would be administered at 7:00 a.m., thereby maintaining their daily routine as well as remaining in compliance the methodological patterns of the study.
Data are expressed as mean and standard deviation. The Smirnov-Kolmogorov test was used to test data normality, using a significance level of 5%. As this procedure indicated that the data did not conform to the Gauss curve, a Kruskal-Wallis test was then performed to examine the differences between the mean heart rates during exercises EX2, EX11 and EX23 (with a confidence level of 5%). These procedures were developed with the aid of an Excel 2003 spreadsheet and the statistical software SPSS 13.0.
The blood pressure at rest for the EX2 session was 126.5 ± 7 mmHg for the systolic, and 77.5 ± 8 mmHg for the diastolic rates. For EX11, the values of systolic and diastolic blood pressure were 130 ± 7 mmHg and 82 ± 7 mmHg, respectively. The respective values for EX23were 129 ± 7 mmHg and 82 ± 8 mmHg. At the end of the exercise, the subjects showed an increase in systolic pressure of 12.7 ± 7; 14 ± 7; and 8 ± 7 mmHg for the at rest values of EX2, EX11 and EX23, respectively. The variations of the systolic pressure for these same sessions were 2.0 ± 5; -3.3 ± 4; and 4.7 ± 2 mmHg.
Table I presents the heart rate at rest of the subjects over the three days of physical exercise. The statistical test revealed that there was no significant difference between the values of heart rate in the three situations (p>0.05).
The behavior during the physical exercise is shown in FIGURE 1. A significantly lower heart rate was observed during the exercise carried out in the plasmatic concentration peak of BB (EX2), compared to EX23, when the subjects had not yet administered the drug that day. It also differed from EX11, when the active substance was already being excreted from the subjects' body, according to the BB pharmacodynamics (Couto, 1998). The difference between the sessions EX2 and EX23 was 10.9%, while in EX11, there was a reduction of 10.3%.
In contrast to the results found in the BB group, the subjects of the control group exhibited responses similar to the heart rate at rest at ten, twenty, thirty and forty minutes of exercise, with no statistical differences between the HR measures among the three exercise sessions. Results are shown in Figure 2.
Absolute variation of heart rate during exercise was observed by subtracting the mean values at ten, twenty, thirty and forty minutes from the basal values. Figure 3a, shows results in the experimental group, where a statistically significant difference was observed at ten, twenty and thirty minutes of exercise in the sessions EX11 and EX23, compared to session EX2 (p<0.05). No significant difference in the absolute variation of heart rate was found among the three sessions in the control group (p>0.05).
The present study data confirm previous information that the BB drug provokes changes in the heart rate which interfere in the chronotropic response during physical exercise (Wonisch et al., 2003; Stoschitzky et al., 2006; Stoschitzky et al., 2004; Derman et al., 1993; Pokan et al., 1999; Van Baak, 1988; Tesch, 1985). Nevertheless, this study demonstrates for the first time that the chronotropic change induced by beta-blockers does not persist throughout the day after being administered, but instead is attenuated when the exercise is performed outside the BB's plasmatic half-life.
The subjects' arterial pressure was found to be lower at the EX2 point, when the drug had reached its plasmatic half-life. Although higher than during the other two points, these values were always controlled within the parameters of 140/90mmHg, as recommended by the SBC (1997). Although the exercise had been performed both in and outside of beta-blocker plasmatic half-life, the arterial pressure response was considered physiological in the three exercise sessions.
The control of the treadmill walk velocity, room temperature and the relative air humidity eliminates the possibility that these variables influenced the heart rate differences that were found in the session EX2 (compared to EX11 and EX23). The control group data confirm that this heart rate variation did not occur due to metabolic, neural or hormonal oscillations, but instead resulted from the time of day the three exercise sessions were performed.
Derman et al. (1993) reported that atenolol and propranolol reduced the heart rate in physical exercise by 21.9% and 14.6%, respectively, in comparison to other similar exercise sessions conducted without using these drugs. These values are greater than the 10.9% and 10.3% heart rate reduction in the exercises performed at eleven and twenty-three hours after the drug was ingested, compared to the exercise performed two hours after BB administration (plasmatic half-life period) in the present study. This smaller chronotropic attenuation may have occurred because of the fact that, in the exercises EX11 and EX23, the subjects were still under some BB effect, even though this was outside the plasmatic half-life period. Nonetheless, this confirms the hypothesis that the chronotropic change induced by BB in exercise depends on the time of drug administration and the time chosen to perform the exercise.
Concerning cardiovascular safety, these results showed that 100% of the subjects were kept within the training zone during the exercise in the EX2 procedure (which had the prescription corrected for the BB use). In the procedures EX11 and EX23 however, 40% of the subjects exceeded the target-zone values. Therefore, the present study highlights that the correction equation use must be adjusted for time elapsed between drug administration and the beginning of physical exercise.
According to Tabet et al. (2006), the use of the physical exercise prescription method by means of generic equations can be misunderstood by subjects who use beta-blockers. The most common prescription method by professionals is the use of an ergometer test with those subjects using BB. From the study results, it is recommended that exercise is prescribed only based on hypertensive subjects using this drug daily (Vanzelli et al., 2004). Nonetheless, this policy is also insufficient given that the patient may not perform the exercise at the same time point after drug administration that the ergometer test was conducted. Thus, this procedure proved to be flawed as a correction equation, in that it overlooks the time interval between drug administration and time of exercise.
Monitoring of heart rate during physical exercise is one of the most common methods among physical educators, while beta-blockers are one of the most prescribed anti-hypertensive drugs by physicians. The high prevalence of subjects who combine BB and physical exercise increases highlights the importance of this study. Against this background, it is recommended that these findings be widely disseminated among physicians and physical educators.
Bearing in mind that this is the first study to examine the drug's use in relation to time elapsed between administration and beginning of exercise, and taking into consideration the large hypertensive population that uses BB, it is recommended that further research be conducted to increase the knowledge base regarding this phenomenon. Several studies have shown that third-generation BBs have less impact on heart rate and, consequently, on exercise tolerance (Weiss, 2006; Veverka et al., 2006; Kuroedov et al., 2004; Van Bortel and Van Baak, 1992). It is additionally recommended that new studies be conducted involving other third-generation BB, such as carvedilol and nebivolol, to determine if there are similar differences in the heart rate decrease, as well as to verify the negative chronotropic effect at various points in the day.
This study used doses of 25, 40 and 50 mg. However, because of the small sample size, it was not possible to correlate dose with chronotropic response. Further studies using a larger sample size are warranted to verify this correlation.
These finding emphasize that the chronotropic change phenomenon demonstrated by the beta-blockers should be studied in order to guarantee exercise prescription accuracy and quality among the large hypertensive population in use of this drug as part of their anti-hypertensive therapies.
By confirming the small positive chronotropic effect induced by the BB, this study reinforces the need for heart rate correction among hypertensive users of BB, as suggested by Brazilian Society of Cardiology. Nevertheless, the data obtained revealed that this chronotropic effect is significantly weaker after the plasmatic half-life period, and that exercise prescriptions must consider the time interval between BB administration and time of exercise activity.
Received for publication on 09th September 2008.
Accepted for publication on 30th March 2009.


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The country, the world economy, your stock portfolio, your job security, your mortgage application, your Social Security application, and—heck—almost anything touched in some way by the federal government could lose from the current budget and debt ceiling battle.
But, amazingly, three senators appear to be coming out of this fiasco as winners. The Senate is expected on Friday to hold a procedural vote clearing the way to pass a temporary spending bill that prevents much of the government from closing on Oct. 1. Their bill would restore funding for Obamacare, something that House Republicans tried to eliminate in their bill passed last week to keep the government open.
Senate Majority Leader Harry Reid (D-NV) – Few others have emerged from this crisis with more authority than Reid, who seems to have evolved into a quasi-LBJ "Master of the Senate" with his command of procedure and ability to hold his caucus together.
The Nevada Democrat has skillfully laid the blame on Tea Partiers for a possible shutdown, while specifically praising Republican senators such as Arizona's John McCain for their respectful opposition. His control—thus far—of the chamber's schedule seems like a marked contrast to the chaos in the House, where it is unclear what will happen if a temporary spending bill is returned that protects Obamacare.
"Every hour that ticks by puts us closer to a shutdown," Reid said on Thursday, noting that he would like to have already returned an amending temporary spending bill back to the other side of Capitol Hill.
By casting himself as a lawmaker who plays by the rules, Reid has also embraced the concept of following the rule of law, which—like it or not—since 2010 includes Obamacare.
This is an issue where the American people are on Reid's side. According to the new CBS/New York Times poll, 56 percent of the country thinks Congress should "uphold" Obamacare "and make it work." It's one of the few issues in polling about Obamacare that enjoys overwhelming support from independents.
Sen. Ted Cruz (R-TX) – Cruz can be a social leper to many of his Republican colleagues. His quixotic quest to defund Obamacare can fail in the Senate. But the freshman Texas senator is emerging from this fiasco looking like Grade-A presidential beef to his Tea Party fans.
Cruz occupied the national stage for the past month. He helped goad House Republicans into passing a bill that defunds Obamacare in return for approving expenditures that keep the government open through Dec. 15. Cruz then spoke against Obamacare this week for 21 hours, and plans to use a filibuster threat on Friday to stop the Senate from passing an amended bill with a simple majority that protects the health insurance program.
Conservative radio show host Rush Limbaugh praised his tenacity, regardless of whether Cruz succeeds legislatively.
Similar compliments have come from Fox News talker Sean Hannity, Blaze firebrand Glen Beck, and other media commentators with loyal Republican audiences.
It will be worth monitoring how much of a bump Cruz gets from his initiative. A recent CNN poll places him sixth in a possible 2016 GOP presidential field with 7 percent, while Public Policy Polling has him fifth in the key primary state of New Hampshire with 10 percent of the vote.
Senate Minority Leader Mitch McConnell (R-KY) - Once again, McConnell has set himself up to be the adult in this confrontation, just as he did in the 2011 debt ceiling showdown and last winter's fiscal cliff crisis.
Until recently, McConnell looked more pre-occupied with defending his seat next year from Tea Party primary challenger Matt Bevin. But McConnell seized the reins inside the Senate this week to block a brash effort by Cruz to bully other Republicans into filibustering any spending bill that doesn't defund Obamacare.
Opposing Tea Party types carries a substantial risk, but he displayed his grasp of legislative nuances to overcome the blunt rhetoric of Cruz's 21-hour talk-a-thon that lasted until Wednesday afternoon. McConnell knows that in the event of a stalemate—which is what Cruz and House Republicans are effectively pushing—the Obamacare health insurance exchanges open as scheduled on Oct. 1.
McConnell was careful not to personally attack Cruz, but merely made a factual statement about strategy.
Why It's Easy to Find Winners in the Senate – This is ultimately a fight between Obama and House Republicans, one in which the Senate can claim to have been entirely reasonable by standing against both a shutdown and a default.
Both the president and House Speaker John Boehner (R-OH) could take the blame for an economic meltdown if no deals materialize in the next few days on spending, or if we reach Oct. 17 and the government—unable to legally borrow—starts to default on its obligations.
The legislative calendar is set up so that the House might have to accept or reject the temporary spending measure from the Senate. That bill is expected to restore funding for Obamacare and finance the government through Nov. 15, at which point Boehner faces the choice of sticking his caucus or forging a deal.
The speaker is holding his cards close to his vest. "We have no interest in seeing a government shutdown," he said Thursday. "There will be options available to us.
Obama has a 44.2 percent approval rating, according to the average of polls tracked by RealClearPolitics. His favorability last plunged to that level after the 2011 debt ceiling showdown, where a crisis was narrowly averted. But two years ago, Obama was still willing to negotiate with Republicans.
He now refuses to bargain over "the full faith and credit" of the United States. If this stonewalling triggers another financial catastrophe, this will be a red line that will easily come back to haunt Obama.