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The reservations centered around a feeling in the Council that the restaurant restrictions would harm businesses

It was no surprise that a legislator representing the Hampton Roads area , like Sen. Northam, would support smoking restriction legislation. Most of the localities in that area were considering asking the General Assembly to pass legislation giving their locality the power to enact some sort of local restaurant smoking restriction and Norfolk had been seriously considering enacting local restaurant restrictions under the assumption that preemption did not apply to their municipality until backing off the proposal in 2008 .Lawmakers representing the Hampton Roads area, including Sen. Northam; Sen. Quayle and Sen. Mamie Locke also pushed for statewide laws that either repealed preemption statewide or allowed their locality greater authority to regulate smoking.On January 25, 2008, House Speaker William Howell referred all of the smoking related bills to General Laws Committee, notoriously hostile to tobacco-control legislation.Howell had close financial ties with the tobacco industry, having accepted $10,000 in campaign contributions since becoming Speaker in 2003.This is significantly more than the median tobacco industry campaign contribution to House Republicans from 1999-2007 . Del. Terrie Suit , who had previously supported Gov. Kaine’s restaurant smoking restriction proposal in the 2007 session, chaired the General Laws Committee. According to House rules, Del. Suit in her role as chair of the committee could have asked to have a bill brought before the full committee by using House Rule 18. Despite the fact that Del. Suit represented an area with a high support 250 for restaurant smoking restrictions, she refused to allow the bills to come before the full committee and instead funneled them into the hostile Alcoholic Beverage Control/Gaming Subcommittee ,indoor grow rack where they were all killed after no further action was taken.An editorial in the Virginian-Pilot questioned why her position had changed and raised several points as potential answers.

Del. Suit maintained that her support waned when many local restaurants in her district voluntarily went smoke free. The editors pointed out that many other areas, including whole communities in her district like Saxis, Big Stone Gap, and others, had very few smoke free choices. Despite the fact that Del. Suit did not accept, and on one occasion returned, tobacco industry contributions, she did owe her chair personship of the General Laws Committee to Speaker Howell. Public health advocates felt the same way. As Cathleen Grzesiek, co-chair of VFHF, described, once Suit “became chair of [the] General Laws [Committee] … all of a sudden she no longer supported clean indoor air laws.”Tobacco control advocates from the Virginia Beach area turned up the political heat on Del. Suit after realizing that she had the power to determine whether these bills were to die in committee. The primary group that pressured Suit was the Virginia Beach Restaurant Association , which urged its members — who were constituents of Del. Suit in the South Hampton Roads area — to tell her to reverse her decision.In addition, the VBRA took out a full-page ad in the Virginian-Pilot urging readers to pressure Del. Suit to move the bill out of subcommittee for the consideration of the full General Laws Committee.Noting that it seemed unfair that just seven legislators could keep a bill from the other 93 members of the House and that there seemed to be broad legislative support for such a bill, a past president of the VBRA stated that “we [the VBRA] feel all representatives should have a chance to vote on it.”Meanwhile, other hospitality industry groups, including the Virginia Hospitality and Travel Association, remained opposed to the bill.VFHF also employed phone banking to target Suit, as well as Speaker William Howell, Dels. Thomas Gear and David Albo who were members of the ABC/Gaming subcommittee. The primary activity against Suit, however, came from the VBRA.Advocates were outraged that the bills ended up in the ABC/Gaming subcommittee. Hilton Oliver, the executive director of Virginia GASP, said “[t]he issue of smoking in restaurants has nothing to do with ABC and gaming, but it has a lot to do with health.

They are playing games [there in the House], no question about it.”Virginia politics and the influence of Speaker Howell had placed the anti-smoking bills into hostile committees, like many other times before. VFHF held that at a minimum, the bills deserved a fair hearing by the full committee.The debate mirrored the same arguments that had been made in Virginia ever since the issue of smoking restrictions first emerged in the 1970s. Many on the General Laws Committee continued to point toward free market principles to justify opposing the legislation. For example, Del. Gear argued, “[i]t’s wrong for government to intervene and tell restaurants they have to do something.”Del. Suit argued that the General Assembly did not need to act on the proposal and that voluntary smoking restrictions were already happening.She stated “[t]wo years ago … I couldn’t find a restaurant that was smoke free. But because of this debate, the whole issue over the last few years has been elevated to the level that so many restaurants have gone smoke free, I no longer believe it’s necessary for the government to step in and do it.”As before, representatives from the Virginia Retail Merchants Association, Virginia Hospitality and Travel Association, and Cigar Association of Virginia spoke of the bill in terms of “choice and property owners’ rights.”Nathan Jones, a Richmond resident and owner of 13 restaurant franchises, claimed that a restaurant law in Indiana caused a 10- 15% drop in alcohol sales, which Mr. Jones claimed could “kill a small business” in a year.These often-repeated claims about the harm to small business interests from tobacco restrictions – the centerpiece of the tobacco industry’s efforts to generate local opposition to such laws since the 1980s – are false.In particular, a 2003 analysis of all the research on the economic impact of smoking restrictions on the hospitality industry, including bars and restaurants, showed no negative impact on revenue.Despite the pressure from several sides, Del. Suit did not change her position, and the legislative session ended in March with no tobacco restriction bills surviving.All the tobacco control bills before the ABC/General Laws Subcommittee were defeated unanimously by voice vote rather than a recorded vote.The reason, according to Gov. Kaine after the vote occurred, was that “[t]hese guys don’t want to be on the record on a matter like that.”Norfolk enacted their original smoking ordinance in 1988, which provided for nonsmoking sections in restaurants and many other public places, and prohibited smoking completely in many retail stores.

This made it stronger than the subsequent state law passed in 1990. In May 2006, Theresa Whibley, a physician,vertical growing racks was elected to the Norfolk City Council. After being elected, Whibley began to push for an ordinance that would that would completely prohibit smoking in restaurants after reading the 2006 Surgeon General’s Report “The Health Consequences of Involuntary Exposure to Tobacco Smoke,” which among other findings reported that eliminating indoor smoking fully protects nonsmokers from harmful effects, while ventilation and separation of smokers from nonsmokers within an enclosed space did not.What Whibley read in the Surgeon General’s Report dovetailed with her personal convictions and experience as a physician that second hand smoke was harmful.No other Hampton Roads area city had smoking restrictions at the time and Whibley felt that the city “need[ed] to take the lead” on the restaurant smoking issue.When she joined the Norfolk City Council, she began inquiring whether the Council could prohibit smoking in restaurants.Whibley sought help from City Attorney Bernard Pishko, who informed her that Norfolk’s charter allowed the city to implement a restaurant smoking restriction without requiring permission of the General Assembly. Pishko argued that neither Dillon’s Rule nor the preemptive language of the VICAA impinged upon Norfolk’s inherent police powers granted by its charter. Therefore, any ordinance that correctly invoked Norfolk’s police powers would be valid. While the VICAA explicitly preempted stronger local regulation of restaurants or bars, Whibley and Pishko had compiled a great deal of evidence that demonstrated that no level of secondhand smoke exposure was safe, and that because of this no law that required no-smoking sections could adequately protect the health and welfare of patrons or workers.Based on this fact, the Norfolk city attorney’s office drafted language for the proposed ordinance that simply required any nonsmoking area to be “effective.” Because the only effective protection for workers and patrons would be a 100% smoke free interior space, Whibley and Pishko were confident that their “effectiveness” language was a valid exercise of the city’s police powers.

Both Pishko and Whibley expected the ordinance to be challenged in court if enacted but felt that they could argue successfully that this approach was consistent with both Dillon’s Rule and the requirements of the VICAA. Whibley and Pishko were the primary motivators for the proposed ordinance, but, after learning about their proposal, the Virginia chapters of the national voluntary health organizations offered material support and publicity, primarily to identify and promote restaurants that were smoke free.After discussing the idea with the City Council in December 2006, the Council voted to endorse the idea but to hold off on enacting any ordinance until it became the results of the debate about statewide legislation affecting restaurants would be.City Manager Regina Williams scheduled hearings in January, 2007 for restaurant owners to address their concerns, as a majority of restaurateurs had come out as opposed to the ordinance, primarily based on concerns that the ordinance would harm their business. These concerns were echoed by some on the Council, such as Vice Mayor Paul Riddick, who was concerned that it would affect the livelihoods of small business owners.The Norfolk Restaurant Association opposed the proposed ordinance, but in a 2009 interview Whibley characterized their complaints as not very vociferous.On July 10, the state Attorney General’s office released an opinion by Virginia Attorney General Bob McDonnell that stated that such restrictions would violate the VICAA’s preemption language, which was issued in response to a request from Del. Bill Janis . In response, Norfolk’s City Attorney, Bernard Pishko, told the press his opinion was that the police powers inherent in Norfolk’s charter were sufficient to allow the restrictions to be implemented without asking the General Assembly for permission.In August 2007 the City Council decided to go forward with their plans to restrict smoking in restaurants within the city despite McDonnell’s opinion, based on Pishko’s advice to the council that it made no difference as to their ability to enact stronger local restaurant restrictions.In October 2007, the Council voted 7-1 to implement an ordinance that completely prohibited smoking in restaurants and bars . As passed, the 2007 ordinance was significantly stronger than state law, completely prohibiting smoking in restaurants and bars, with an exception only for establishments conducting a private function in the entire space. It maintained many of the other provisions of the 1988 ordinance. By completely prohibiting smoking in restaurants or bars, Norfolk’s ordinance not only would have protected the health of workers and patrons, but it was also significantly stronger than the 2009 statewide legislation, which allowed for both smoking rooms and ventilation. However, the ordinance would not have gone into effect until July 2008, and before that date arrived the Council shifted its position in early 2008 on the restaurant smoking restriction issue. Five council members rethought their support, citing the failure of statewide or regional smoking restrictions in the General Assembly.Barclay Winn, a council member whose interactions with Virginia Beach led to the Hampton Roads regional approach, said that he wanted a “minor revision for sports bars … I just want to be sure we get a level playing field.”Another council member, Vice Mayor Anthony Burfoot, wanted to include a provision that allowed restaurants the ability to appeal the restriction if they can show resulting economic damage.Council member W. Randy Wright felt that the Council “can’t put our establishments at a competitive disadvantage.”As the five council members backpedaled, Whibley expressed frustration and hoped that the law would be implemented unchanged.Ultimately, despite Whibley’s efforts, the Council moved steadily towards a vote rescinding their earlier ordinance. At the end of March 2008, the Council voted to rescind the restriction, partially because it seemed that a statewide restaurant smoking restriction would soon pass .

It is worth noting that the current interface to the Island requires no typing beyond the initial login

There is a flat list of the 175 tasks currently available with few constraints on how they can be used. This gives students freedom in the experiments they design. Some of the tasks apply treatments, such as giving the subject a tablet containing 1 mg of alprazolam or making them swim freestyle for 200 m. These do not show any output in the interface but the tasks have changed the state of the Islander in the simulation. Since the simulation happens in real time the students need to wait to observe effects. Other tasks then produce data, such as measuring blood pressure or pulse rate, or taking a blood or urine sample to detect a particular substance. The onus is on the student to develop the protocol for applying the treatments and making the measurements. In addition to tasks that mostly behaved like measurements, the students could also design a survey for their Islanders to complete. Questions that students were interested in asking were added to the system, along with a range of standard survey questions that we typically ask the students themselves . The Islanders would take longer to complete longer surveys, discouraging students from just asking all the questions. Some Islanders were predisposed to lie on the surveys,vertical farm systems particular for questions related to age and weight. Students can always tell they are lying because the actual age of each Islander is displayed on the profile and there is a measurement task for weighing an Islander. There is also a chance that an Islander will decline to respond to a survey. This chance varies between the different cultural groups on the Island making a pattern in non-response bias for students to explore.

The instructor can see all tasks assigned by an individual student to each Islander they used as well as Islanders that have been visited by the student but who have not had any tasks assigned to them . These monitoring tools provide a useful level of accountability for individual student work and also give the instructor a broad insight into how the environment is being used by their class.Villages and individuals, tasks and results are all navigated through mouse clicks on a web browser. This has made the Island well suited to the many mobile devices that now have touchscreen interfaces. For example, although it was released after the Island was conceived, the iPad has been an ideal hardware interface to the Island. Mobile devices are also useful with the Island since the experimental simulations run in real time. For example, students can allocate their treatments to subjects during group work in a computer lab and are then able to check on the subjects, such as monitoring blood pressure or some hormone level, while riding on a bus. The Islanders have a pair of chromosomes that they inherit in the usual way from their parents. The 256 ‘genes’ on each these chromosomes are used to determine a variety of attributes, including the physical characteristics seen in Figures 1, measures of disease susceptibility, and other parameters required by the task simulations described in Section 3.2. We give students access to this genetic information through a task that generates the analog of a micro-array image for one or both of the chromosomes. Students can use this task to carry out studies that mirror micro-array techniques in the real world. For example, Bulmer and Meiring describe a student project that looked for evidence of a gene linked to diabetes on the Island. In that study the student obtained micro-array images for 10 Islanders with diabetes and 10 without, giving the results shown in Figure 3.

The question is whether there is any systematic difference between the intensity levels expressed in each set of images. Figure 4 shows a more quantitative summary of the results with side-by-side box plots for each of the 256 genes appearing in the micro-arrays. For convenience we label the positions with B000 at top left, along to B015 at top right and then continuing by rows to B255 at bottom right. The student carried out a two-sample t test to compare the levels between the subjects with diabetes and those without for each of these. The four strongest effects were for genes B116 , B041 , B186 and B118 . Figure 5 shows the box plots for these four comparisons in more detail. For B116 the intensity distribution for non-diabetics seems uniform while it appears systematically lower for diabetics. We now use this student study as an example in class. Of course the p-value for B116 needs to be treated by caution since it arose from a large number of multiple comparisons. In our introductory course we use the very conservative Bonferroni adjustment to the p-values, whereby B116 becomes non-significant, but the overall example illustrates to students the practical issues involved in this kind of screening as well as an area of current research in the discipline of statistics itself. A great advantage of this approach is that new students can replicate the study if they want, or search for other similar genes.Our final example illustrates the open-endedness of the Island through a new measurement devised by a student based on the existing data. The student was interested in possible risk factors for smoking and she wanted to test the hypothesis that major life-changing events could increase the incidence of smoking due to stress. Using a sample of 40 Islanders, she counted the number of life-changing events each of them had experienced. She defined these to be any of illnesses, marriages, child births, loss of spouses and migration between villages. She recorded their current smoking status and then looked for a relationship between the two variables. A logistic model for the relationship is shown in Figure 6. This was an interesting outcome for the student since the conclusion was the opposite of her original hypothesis: there was significant evidence that Islanders with higher numbers of life-changing events were actually less likely to be smokers. However it was also a very interesting outcome for the authors because this relationship was not an explicit part of any of the simulation models.

This emergent phenomenon is most likely an example of survival bias in the results since smokers tend to die younger and so ultimately have less time to experience life-changing events. Future students can replicate this study and try to adjust for age, for example, to confirm whether this is the case. Student feedback to the Island has been very positive. In our context the role of it has been to replace real experiments and this is reflected in many comments such as that “they were interesting and a great way to find results of experiments. It made the experimentation process nice and easy to conduct”. However students were also engaged with the Islanders beyond a basic tool for generating data: “I liked how we were able to see their whole history on their profiles; it was interesting seeing some of their troubled past”. As mentioned earlier, we do have a tension between reality and fantasy in our design and it was interesting to read comments on the reality aspect, such as that “the Islanders were a little too real,vertical farming cost especially as they improved reaction times after repeating the action. We really had to think of them as real people – which I suppose was the whole point”. In contrast there have not been open comments on the ‘unreal’ aspects, such as the Islanders with elven ears or the unusual disease names. We suspect that students are used to these features in computer games and are not surprised by them. This is an interesting area for future studies. The consistent negative feedback has been on the Islanders sleeping each night. While some students were interested in studying sleep, as in the dextroamphetamine example above, for the majority of students the fact that the Islanders go into an uninterruptible sleep each night is often a nuisance. At this stage we are continuing to include this constraint, as part of our general philosophy summarized in the following section. However we have made the Islanders go to bed a bit later each night and have introduced some tasks that can be performed on sleeping Islanders, such as the various blood tests and a simple polysomnography tool, so that students are not completely stuck if they have left their project until the night before it is due. In general it is not surprising that the Island has been successful in engaging students with the task for which it was designed. We are interested now in evaluations from other users of the Island in contexts different from our own. For example, Linden et al.give outcomes of a research grant that has investigated the use of the Island as a tool in teaching clinical trial design and management. Edwards and Crowther give an evaluation of the Island in a health systems management course where the focus was not on statistical reasoning at all. Such projects give insight into the transferability of the tool while also feeding back ideas to further expand the models included in the simulated environment. Bulmer gives more details regarding this collaborative approach. Various preparations of the leaves, flowers and resinous extracts of the Cannabis plant have been consumed for both medical and recreational purposes since antiquity. Extensive research efforts aiming to explain the widespread therapeutic and behavioral effects evoked by Cannabis consumption finally led to the discovery of a new messenger system called the endocannabinoid system. It is composed of the CB1 and CB2 cannabinoid receptors , which are not only targets of the psychoactive compounds of the Cannabis plant, but more importantly, they are also activated by two endogenous lipid molecules produced by most cell types in the body . The mobilization and elimination of these two endocannabinoid molecules called N arachidonoylethanolamine and 2-arachidonoylglycerol are tightly regulated by surprisingly complex networks of metabolic enzymes and pathways in different cell types and tissues .

Following the clinical failure of brain-penetrating CB1 receptor antagonists as therapeutics due to adverse psychiatric effects, the identification of novel molecular players regulating endocannabinoid levels has opened new possibilities, because drugs targeting these enzymes may have more selective actions . The wide spectrum of human neurological and psychiatric diseases in which the endocannabinoid system is implicated suggests a vast therapeutic potential . However, to take advantage of this potential requires full characterization of the enzymes regulating endocannabinoid signaling in the human brain. A conceptual framework describing the major aspects of neuronal endocannabinoid signaling has emerged from the results of numerous animal studies in the last decade. In contrast to conventional neurotransmitters, endocannabinoids are primarily synthesized and released by postsynaptic neurons in an on-demand manner , and subsequently activate presynaptically located CB1 cannabinoid receptors, thereby regulating neurotransmitter release from several types of axon terminals . This retrograde manner of synaptic endocannabinoid signaling is indispensable for various forms of homo- and heterosynaptic plasticity throughout the central nervous system , and probably accounts for the extensive involvement of the endocannabinoid system in brain disorders . Thus, molecular mechanisms regulating synaptic endocannabinoid signaling may be of pivotal importance in the therapeutic exploitation of the endocannabinoid system. Although anandamide is the archetypical endocannabinoid molecule , and may tonically control presynaptic CB1 receptors , most experimental evidence converge on the notion that 2-AG is the crucial retrograde messenger mediating on-demand forms of short- and long-term synaptic depression through CB1 activation. Pharmacological inhibition of diacylglycerol lipase, including its alpha isoform, the enzyme primarily responsible for 2-AG biosynthesis in adult brain , prevents retrograde endocannabinoid signaling in various experimental paradigms throughout the cerebral cortex . Particularly compelling support for this concept also derives from the genetic inactivation of DGL-α, which completely abolishes endocannabinoid-mediated synaptic plasticity, for example in the hippocampus . Conversely, pharmacological blockade of monoacylglycerol lipase , the enzyme responsible for inactivation of the major fraction of 2-AG in the brain , prolongs retrograde endocannabinoid signaling in distinct types of synapses . Widespread distribution of 2-AG in the human brain has recently been revealed with a largely overlapping regional pattern to CB1 receptors based on radioligand binding and in situ hybridization experiments .