Software Defined Wireless Rechargeable Sensor Networks (SDWRSNs) are an inexorable trend for Wireless Sensor Networks (WSNs), including Wireless Rechargeable Sensor Network (WRSNs). However, the traditional network devices cannot be completely substituted in the short term. Hybrid SDWRSNs, where software defined devices and traditional devices coexist, will last for a long time. Hybrid SDWRSNs bring new challenges as well as opportunities for energy saving issues, which is still a key problem considering that the wireless chargers are also exhaustible, especially in some rigid environment out of the main supply. Numerous energy saving schemes for WSNs, or even some works for WRSNs, are no longer suitable for the new features of hybrid SDWRSNs. To solve this problem, this paper puts forward an Energy-saving Traffic Scheduling (ETS) algorithm. The ETS algorithm adequately considers the new characters in hybrid SDWRSNs, and takes advantage of the Software Defined Networking (SDN) controller’s direct control ability on SDN nodes and indirect control ability on normal nodes. The simulation results show that, comparing with traditional Minimum Transmission Energy (MTE) protocol, ETS can substantially improve the energy efficiency in hybrid SDWRSNs for up to 20–40% while ensuring feasible data delay. Wireless Sensor Networks (WSNs) usually suffer from the limitation of energy supply, especially in some rigid application environments, such as hydrological monitoring, disaster warning, mountain battlefield spying, etc. Consequently, the emerging Wireless Rechargeable Sensor Networks (WRSN) ,2, as a However, in many applications, the wireless charger’s energy is also limited. To demonstrate this issue, d from the wireless charger to the energy receiver [Since the charging efficiency is inversely proportional to the square of distance receiver , the samAt the same time, the combining of Software Defined Networking (SDN) and WRSNs , which i(1)The lifetime of each node is no longer a key problem. Their energy can be supplemented by the wireless charger in time. On the contrary, the total energy consumption of all nodes, or the burden of the wireless charger turns out to be a key problem.(2)The energy consumption model is different. The geographical distribution of sensor nodes will directly impact the charging efficiency, and thereby change the burden of the wireless charger.(3)Although the SDN controller can only directly control the SDN nodes to optimize the traffic and energy consumption, this will indirectly influence the inlet flow of normal nodes, and thus change the behaviours of normal nodes indirectly.Consequently, in the context of hybrid SDWRSNs, the energy saving problem is quite different comparing to normal WSNS, or even normal WRSNs, as follows:Existing studies, which will be demonstrated particularly in To solve the above problem, in this paper, we put forward an Energy-saving Traffic Scheduling (ETS) algorithm for hybrid SDWRSNs. The ETS algorithm adequately considers the new characters in hybrid SDWRSNs and takes advantage of the SDN controller’s direct control ability on SDN nodes and indirect control ability on normal nodes. The simulation results show that ETS can substantially improve the energy efficiency in hybrid SDWRSNs, and therefore ensure the network working more steadily and chronically. We highlight our contributions of this paper as follows:Firstly, we derive a mathematical optimization model for the energy efficiency problem in hybrid SDWRSNs. Although it proved to be a non-deterministic polynomial hard (NP-hard) problem, the model provides an outline and paradigm for energy saving problem in hybrid SDWRSNs.Then, a fast heuristic algorithm known as Energy-saving Traffic Scheduling (ETS) is presented, which takes charging losses and the new energy saving characters into account, and schedules the flows through both SDN nodes (directly) and normal nodes (indirectly).Finally, we evaluate the performance of the ETS algorithm with simulations. Compared with traditional Minimum Transmission Energy (MTE) protocol, ETS has a much better effect on reducing energy consumption when ensuring feasible data delays.The remainder of this paper is organized as follows. The related work is reviewed in To the best of our knowledge, so far there is no work concentrated on energy saving problems in hybrid SDWRSNs. Some related works, which establish a foundation for this problem, can be classified into three categories, as follows.The energy limitation is always a key problem for various WSNs. A lot of work has been done to reduce energy consumption and prolong the lifetime of WSNs. These studies usually focus on optimizing network deployment ,6,7,8, pAt the same time, researchers have explored various methods to acquire sufficient energy for WSNs with the method of energy harvesting. Refs. ,21 proviThese energy harvesting techniques are the basis of WRSNs, and the new charging pattern should be fully considered in the design of energy saving scheme for hybrid SDWRSNs.In the wireless rechargeable sensor networks, the energy efficiency issue is still a key problem. In , the potThe sensor nodes and energy charger may be fixed in preset locations. In this situation, existing methods to improve the energy efficiency are mainly by optimizing the deployment of chargers. In , researcHowever, all the above studies on energy saving in WRSNs try to save energy through optimized deployment of wireless chargers. The energy saving scheme of traffic scheduling is still a blank for WRSNs.In summary, current studies on energy saving for WSNs or WRSNs are not suitable for hybrid SDWRSNs. New schemes are urgent to be developed to satisfy the energy saving requirement in hybrid SDWRSNs.As shown in Basically, there are two kinds of relay nodes: normal relay node  and SDN relay node (or shorted as SDN node). The normal nodes run traditional routing protocols, such as MTE, Ad hoc On-demand Distance Vector Routing (AODV), etc. In this paper, we use MTE as routing protocol among normal nodes, since MTE has good performance in reducing the energy consumption of the WSN nodes. As to the SDN nodes, a common SDN controller can calculate the optimal flow table according to the whole network’s topology and flow distribution. The controller can talk to the SDN nodes via 3G/4G (when a cellular network is available) or some other long distance communication methods such as LoRa . This will not add obvious economic burden since only a part of relay nodes or sensor headers are SDN nodes. In addition, this will not introduce obvious additional energy consumption in the pattern discussed in this paper, as follows: (1) When the locations of the network nodes are static, the network topology is relatively stable. At the same time, the flow characters are usually steady since the services in WSN are generally periodical. (2) The update of the flow table may occur in two patterns: (a) SDN controller can update the flow table periodically. The period can be relatively long, for example, 10 min one time, 1 h one time or even several hours one time; (b) triggered by an event, such as node joining/existing, etc. Therefore, the low frequency update and occasionally triggered update will not introduce obvious additional energy consumption.At the same time, some wireless chargers are deployed in proper locations to replenish the energy consumption of network devices, i.e., sensor nodes, the relay nodes, and the sink node. Consequently, considering that the sensor nodes, the sink node, and the SDN controller work according to their predefined pattern and will not be influenced by the algorithm proposed in this paper, we need not count the energy consumption of these three parts, and concentrate on the algorithm’s effect on the relay nodes.In this section, we firstly derive the node energy consumption model, and then present the mathematical optimization model of the traffic scheduling problem in hybrid SDWRSNs.v that receives data from some node u and transmits data to some other node w in a time span t, there are four states: transmitting state, receiving state, idle state and sleeping state. We discuss below the energy consumption of these four states, respectively, referring to the energy consumption model in [For a certain relay node model in .v is sending w, the energy consumption w, which is denoted with v to target w, and there is a threshold (1) Transmitting state. When node Therefore, the energy consumption in transmitting state v is receiving some u. The energy consumption v only concerns about the radio electronics, i.e.,(2) Receiving state. In this state, node u to transmit v, and R is the data rate of the wireless link from node u to node v. Thus, the energy consumption v can be calculated as:v in idle state.(3) Idle state. In this state, the only function for a node is to keep listening to the channel and being ready to receive data. Generally, the idle power consumption (4) Sleeping state. In this state, the energy consumption v, the energy consumption in a time span t is:According to the analysis above, for a relay node c to node v. When radio waves travel in space, their powers attenuate with increased travel distance. The wireless charger usually charges the devices that are not far from itself. Long distance or obstructions may greatly recede the charging efficiency, which can be avoided by deploying more wireless chargers in practice. Consequently, we can adopt free space propagation model. According to Friis’s free space equation, the receive power d is the distance between the source node and the receiver node, and However, in WRSN, what we are really concerned about is the actual energy rce node .v is t, the rest energy in node v’s battery is v to its responsible wireless charger c, c to node v, and v. Considering A is a constant coefficient. Note that, in Equation (t. When (a) follows that t , there quation (PcvtcvA×dv consumes c should consume v). Combining with Equation  in the network and C is the set of wireless chargers. N and D, respectively, represent the subset of normal nodes and the subset of the SDN nodes. The sink node is expressed as s. Obviously, there is In order to get mathematical optimization model of the traffic scheduling problem in hybrid SDWRSNs, we assume v, in a given time span t, the data it transmitted : is on the way from node v to node w and is equal to 1 when it is on that way. Assuming M is an arbitrarily large value and m is an arbitrarily small value, then there are two constraints as below:l is not on the way from node v to node w; on node l, there should be no data sent from node v to node w. When v via node l to node w, then:For the normal nodes that run MTE protocol, the routes they choose have the minimum transmission energy. Assume For MTE, the route for each node is unique, therefore,v, if the energy consumption speed is larger than the energy charging speed, the node will eventually drain out its power and become inactive. To avoid this problem, at any time there should beFrom Equation , to a not Enlarging the amount of sleeping nodes while satisfying the service requirements. Different from traditional energy saving algorithms in normal wireless sensor networks, in the effective charging scope of wireless chargers, ETS does not need to consider energy consumption balance among different nodes, or single node’s lifetime. ETS algorithm converts the energy consumption of each node into the final energy consumption of the wireless charger, and pays attention to minimize the finally total energy consumption.(2)The trade-off among different nodes that would be turned into sleeping state. As described above, the same energy consumption in different nodes will result in a different burden on the whole network, or specifically, to the wireless chargers. The ETS algorithm prefers to turn nodes farther to wireless chargers into sleep so as to decrease the energy loss in charging.(3)The indirect control ability of SDN controllers on normal nodes. In the process of the ETS algorithm, the SDN controller selects the directions of flows on SDN nodes and thus influences the inputted flows on normal nodes, so as to change the normal nodes on the selected path, and achieve a more energy efficient traffic scheduling pattern.As mentioned above, the problem of energy-saving traffic scheduling in hybrid SDWRSNs is NP-hard. To prolong the steadily working time of the networks under new environments, we should fully consider the new characters in hybrid SDWRSNs, and take advantage of the SDN controller’s direct control ability on SDN nodes and indirect control ability on normal nodes. Consequently, based on the above idea as well as the fast heuristic method, in this paper, we propose an Energy-aware Traffic Scheduling (ETS) Algorithm for hybrid SDWRSNs. The ETS Algorithm improves the energy efficiency by more energy efficient traffic scheduling schemes, which mainly solves the following three problems:In this paper, while the SDN nodes choose routes according to the flow table determined by the SDN controller, the normal nodes are running MTE protocol. For convenience, the route calculated according to MTE protocol are called MTE route in this paper. When an MTE route of a certain flow has at least one SDN node, we define this flow as an SDN flow; otherwise, it is a normal flow.Algorithm 1 describes the process framework of ETS. According to current flow distribution and network topology, we choose an MTE route for each flow and judge whether it is an SDN flow or a normal flow. For the normal flows, the SDN controller cannot schedule them directly. Therefore, the nodes on the routes for normal flows must be active. The normal flows should be distributed according to their MTE routes in the first place. Then, for the SDN flows, the first SDN node on its MTE route should be recorded. Algorithms 2 and 3 embody the advantages of SDN nodes provided as compared to the normal nodes, i.e., on the basis of MTE, adjusting the distribution of flows after they arrive the SDN nodes. Algorithm 2 is used to find all the optional paths (as defined in Definition 1) for an SDN flow. In order to take the energy consumed by wireless chargers into account, the actual transmitting energy Algorithm 1 Energy-Saving Traffic SchedulingInput: V, the set of wireless chargers C, the set of flows FThe set of nodes Output: AThe set of nodes in working state 1:Initialize: 2:Find the MTE routes for each 3:for each do4:iff is an SDN flow then  5:n is the nodes on the MTE route from the source node to the first SDN node in flow f;   6:optional paths search function to find the optional paths f;   Run 7:else  8:n is the nodes on the MTE route in flow f;   9:   10:end if  11:end for12:whiledo13:for each do  14:ifthen   15:f;    16:    17:end if   18:end for  19:optional path selection function to find an optional path f;  Run 20:  21:f;  Update the size of flow 22:if the size of flow f equals to 0 then  23:   24:end if  25:end while26:returnA.When the amount of SDN nodes increases, there may be multiple SDN nodes in an optional path. If we search the optional paths on every SDN node in the path, it will be considerably complicated to find all the optional paths with a high computational complexity. Consequently, to simplify the calculation, except the first SDN node, the rest SDN nodes on this route do not try to optimize the route again. Therefore, the optional paths for an SDN flow is the acyclic MTE routes from the direct neighbours of the first SDN node to the destination.Algorithm 2 Optional Paths Search FunctionInput: f, the first SDN node s on the MTE route of f, the set of neighbours of sA flow Output: The set of optional paths 1:for each do2:v to the destination of flow f with the actual energy consumption calculated by formula .The optional paths are specifically defined for an SDN flow. When an SDN flow arrives the first SDN node on its MTE route, the optional paths are all the possible routes from this SDN node to the sink node. The next hop of an SDN node on the optional path can be any neighbour of it, and the next hop of a normal node is chosen according to MTE.Each SDN flow has one or more optional paths. For the SDN flows with only one optional path, ETS can directly allocate these flows on their unique optional paths. The nodes on the optional paths should also be in a working state. For the SDN flows with multiple optional paths, Algorithm 3 is designed for them to select an optimal path. Some related parameters are as follows: r: the largest amount of flows that may go through the node. If a node is on the optional path for a flow, then n is the number of nodes on the optional path.In Algorithm 3, we choose one optimal path from the optional paths according to the following sequences: (1) We preferentially choose the path with the minimum Algorithm 3 Optional Path Selection FunctionInput: FThe set of optional paths Output: p and its corresponding flow fA selected optional path 1:for each do2:p;  Calculate the 3:end for4:P in ascending order according to Arrange 5:Initialize 6:fordo7:ifthen  8:   9:end if  10:end for11:Arrange 12:fordo13:ifthen  14:   break;15:end if  16:end for17:returnf.In this section, we evaluate the performance of ETS algorithm via simulations implemented by C++. To ensure the generality of the simulation results, we randomly generate a network as shown in Consequently, the ETS algorithm can achieve obvious energy efficiency compared with the traditional MTE algorithm while ensuring feasible data delay.A mathematical optimization model for the energy efficiency problem in hybrid SDWRSNs is derived, which provides an outline and paradigm for energy saving problem in hybrid SDWRSNs. Then, we put forward an Energy-saving Traffic Scheduling (ETS) algorithm for hybrid SDWRSNs. The ETS algorithm takes charging losses and the new energy efficiency requirements into account, and schedules the flows through both SDN nodes (directly) and normal nodes (indirectly). The simulation results show that ETS can substantially improve the energy efficiency in hybrid SDWRSNs for up to 20–40% compared with traditional routes with feasible data delay. Therefore, ETS can make the network working more steadily and effectively for a much longer term.In this paper, we only use the first SDN node along a source-destination pair, so as to avoid too high algorithm complexity. In future work, some improved algorithm that can employ all SDN nodes along a source-destination pair with low complexity can be studied, which might further improve the energy efficiency while ensuring feasible data delay.


The world's entire scientific and cultural heritage, published over centuries in books and journals, is increasingly being digitized and locked up by a handful of private corporations.-Aaron SwartzScholarly communication began as an interpersonal exchange of findings between fellow researchers . In timeMarket bubbles form when a commodity gets overvalued and its price, unwarranted by intrinsic value, rises. They deflate when the self-perpetuating shared (mis)belief that a commodity will always return benefits, regardless of its cost, gets forced beyond extreme. Scientific information is considered economic commodity, and scholarly publishing behaves in entrepreneurial manner ,4. TurniThe workflow in scholarly publishing involves knowledge producers – scientists, consumers , and publishers, the latter acting as the “middle man” and providing the means of dissemination of goods . In compRepeatedly, from different perspectives and in different forms, researchers and editors call attention to the following list of facts: that most research findings are false , only a The above listed arguments support the notion that scholarly publishing is expanding in all directions, like a bubble. The number of publications and rising prices are the main but not the only problem. There is also high number of publishers, journals, journals per publisher, predatory journals, authorships per article and per unique author, number of references per paper, self-citated and self-citing rates, and so on – they all relentlessly increase -22. ThusEpistemological Letters – a “subversive” physics newsletter created because Bell and his colleagues could not publish their work in major scholarly journals (One of the scientific breakthroughs in 2015 was the Bell´s theorem. It is a theorem in quantum mechanics named after the physicist John Stewart Bell and it has been described as “the most profound discovery in science” . Apart fjournals . HistoryCroatian Medical Journal, a taxpayer-funded no-profit journal, is proud to be part of the diamond OA and it continues to provide a platform for archiving and free exchange of science. Our model serves as an example that small journals can survive in the modern digital era, without losing sovereignty or independence, and keeping a strong emphasis on research integrity. We are not saying that publishers should not get paid, but the price of profit in publishing is too high and if the current publishing practice continues, we are at risk of compromising the one thing publishing was meant to help and serve – science.Bubbles deflate because of paradigm shifts – a radical change in the production process of goods . In case


This study investigated factors that influence emergency medicine (EM) patients’ decisions to participate in clinical trials and whether the impact of these factors differs from those of other medical specialties.A survey was distributed in EM, family medicine (FM), infectious disease (ID), and obstetrics/gynecology (OB/GYN) outpatient waiting areas. Eligibility criteria included those who were 18 years of age or older, active patients on the day of the survey, and able to complete the survey without assistance. We used the Kruskal-Wallis test and ordinal logistic regression analyses to identify differences in participants’ responses.A total of 2,893 eligible subjects were approached, and we included 1,841 surveys in the final analysis. Statistically significant differences (p≤0.009) were found for eight of the ten motivating factors between EM and one or more of the other specialties. Regardless of a patient’s gender, race, and education, the relationship with their doctor was more motivating to patients seen in other specialties than to EM patients . EM’s rankings of “how well the research was explained” and whether “the knowledge learned would benefit others” as their top two motivating factors were similar across other specialties. All nine barriers showed statistically significant differences (p≤0.008) between EM and one or more other specialties. Participants from all specialties indicated “risk of unknown side effects” as their strongest barrier. Regardless of the patients’ race, “time commitment” was considered to be more of a barrier to other specialties when compared to EM . Among the six resources assessed that help patients decide whether to participate in a clinical trial, only one scored statistically significantly different for EM (p<0.001). EM patients ranked “having all material provided in my own language” as the most helpful resource.There are significant differences between EM patients and those of other specialties in the factors that influence their participation in clinical trials. Providing material in the patient’s own language, explaining the study well, and elucidating how their participation might benefit others in the future may help to improve enrollment in EM-based clinical trials. There is strong evidence that clinical research efforts in emergency medicine (EM) are increasing as demonstrated by the recent establishment of the “Office of Emergency Clinical Research” within the National Institutes of Health. EM research results in special challenges as EM patients present without a pre-existing physician-patient relationship and with acute and often-undifferentiated diseases.2Many studies have investigated the factors influencing patient participation in clinical trials from different areas of medicine.10Despite this plethora of studies, there are virtually no data investigating whether these factors vary by type of clinical specialty. We hypothesized that, based on specialty, these factors’ influence would indeed vary: e.g., factors influential for oncology patients would not necessarily be similar for obstetric patients. Likewise, EM patients, being under a complex array of physical and psychological stressors, might perceive each motivator and barrier differently when considering participation in a clinical trial.Since it would be beneficial for EM researchers to know what matters to their patients and how to use this knowledge to customize and optimize their recruitment approach, we sought to determine the factors that influence EM patients’ decision to participate in clinical trials and whether their impact varies from other selected medical specialties.This was an institutional review board-approved prospective, cross-sectional, self-administered survey study using a convenience sample of patients attending different medical specialties’ outpatient practices at three hospital sites affiliated with a single health network. In preparation, the principal investigator (PI) contacted various specialties for collaboration. Three agreed to participate: obstetrics and gynecology (OB/GYN), family medicine (FM), and infectious disease (ID). The survey subsequently was conducted in the network’s two OB/GYN clinics, four FM clinics, two ID clinics, and three separate emergency departments (EDs). Surveys were offered only to those patients who were in the waiting rooms of these specialties. Thus, patients who came to the ED via ambulance and/or bypassed the waiting room were not surveyed.Population Health CapsuleWhat do we already know about this issue?Enrollment in clinical trials is particularly challenging in EM as patients often present with acute, undifferentiated diseases, and have no preexisting relationship with providers.What was the research question?What factors influence EM patients to participate in clinical ttrials, and does their impact vary from other specialties?What was the major finding of the study?Impact of several factors that influence EM patients’ participation in research significantly varies from other specialties.How does this improve population health?Enrollment in EM research may improve by providing material in patient’s own language, explaining the study well, and elucidating how their participation might benefit others in the future.The survey was anonymous, voluntary, and administered over a nine-month period . Potential subjects were approached by multilingual research team members who, in addition to English, were fluent in either Spanish, simplified Chinese, or traditional Chinese. Inclusion criteria required participants to be a minimum of 18 years of age, active patients on the day of the survey, and have the ability to complete the survey without assistance.The survey was developed by the EM investigators and reviewed by researchers from the other departments involved, a statistician, and the EM research review committee. Based on their feedback, the survey was revised and piloted among 15 randomly selected non-clinical and non-research hospital staff. A brief questionnaire was given to these pilot participants asking whether they could tell us what the purpose of our survey was, how long it took them to complete it, if any questions were too long or confusing, and to provide their general feedback. The respondents accurately determined the purpose of the survey and felt it was appropriate in length. We redistributed the survey to these pilot participants after a two-week interval and compared their second responses to their first to ensure a rate of 95% consistency in interpretation. Revisions were made as needed.Patients were approached in the “check-in” area of each specialty office by a study team member, were asked their age and, if 18 years of age or older, were offered the survey. Although a cover page explained the purpose of the survey, research staff also provided a brief oral introduction about the survey’s goal, which was to ascertain patients’ opinions about clinical research trials in which doctors test new medications or devices. Confirmation that the patient had not taken the survey on any previous visit to our network’s facilities was obtained. The research staff asked if patients were able to self-administer the survey and, based on their preference, were given a copy of the survey in English or one of the three translated languages. We included in the data analysis only those surveys that indicated the respondent was an active clinic patient.th survey to ensure entry accuracy, consistency of the data entry, and to confirm the integrity of the database.Regarding potential influential factors for research participation, subjects were asked to rate each factor on a five-point Likert scale as having no (0), very little (1), some (2), moderate (3), or greatest (4) significance. Following the administration of the survey, two trained research associates entered the data into Excel spreadsheets. The PI audited every 20We compared demographic variables among specialties using a chi-square test. If a significant association (p<0.05) was found, pairwise comparisons were performed to determine which specialties’ results were significantly different from each other. We applied the Bonferroni correction to account for the multiple pairwise comparisons for each demographic variable; with this correction applied, the p-value required for statistical significance was 0.008 (0.05/6).We used the Kruskal-Wallis test to compare responses for each factor affecting participation in research by specialty. This test is appropriate when comparing two or more groups on an ordinal independent variable.To further explore the association between the specialty in which the patient took the survey and their responses to specific motivational factors and barriers, we performed an ordinal logistic regression. One motivational factor was chosen, “my relationship with my doctor,” on the premise that responses differed significantly between EM and all other specialties. Similarly, the responses for the two barriers that were chosen, “time commitment” and “religious beliefs,” differed significantly between EM and at least two other specialties. The predictors included in the models were gender, race, education, and specialty. We chose gender, race, and education in an attempt to control for confounding of the relationship between specialty, motivator, barriers to participation in clinical research.We collapsed the categories for the responses from five to three levels to ensure large enough cell counts for each predictor by each response variable. The collapsed response categories for the motivational factors were “high or very high,” “moderate,” and “slightly or not motivating at all.” Similarly for the barriers, the collapsed categories were “significant or very significant,” “moderate,” and “slight or not a barrier at all.” After collapsing the response variables, we assessed and met the proportional odds assumption.We screened 2,917 subjects , of whomDemographic characteristics were significantly associated with specialty (p<0.05). EM patients ranked the majority of motivational factors lower than other specialties. Statistically significant differences were found for eight of the ten motivating factors between EM and one or more specialties. Two factors that did not show statistically significant differences between EM and any other specialty were “my desire to please the doctor” and “the doctor conducting the research is the same race/ethnicity as me.” The top two motivating factors for EM patients appeared to be “how well the research is explained to me” and “knowledge learned from my participation will benefit someone in the future” .All nine barriers showed statistically significant differences between EM and one or more specialties. While all patients, including EM, ranked “risk of unknown side effects” as the strongest barrier, one particular barrier, “my family’s concern,” scored slightly higher for EM patients than other specialties .Among six resources assessed that help patients decide whether to participate in a clinical trial, EM patients ranked “having all material provided in my own language” as the most helpful. EM was not statistically different from any other specialty in their rankings of these factors with the exception of whether or not they would be given the opportunity to speak to a patient who has participated in a clinical research study; OB/GYN patients ranked this factor higher (p<0.001) than all other specialties .Regardless of their gender, race and level of education, patients seen in other specialties had higher odds of being motivated by their relationship with their doctor compared to those seen in EM: FM , ID , and OB/GYN .Regardless of race, patients seen in FM , ID , or OB/GYN , females , and those who graduated college or had a higher degree , had higher odds of stating that time commitment was a barrier than those seen in EM, ID, or men, and those with less than a high school education.Regardless of the specialty, women , African Americans , Hispanics , multiracial patients , and patients of other races  all had higher odds of stating that their religious beliefs were more of a barrier when compared to male Whites. Patients who were college graduates or had a higher degree , as well as those with some college or a two year degree , had lower odds of their religious beliefs being a barrier compared to those with less than a high school diploma.Although EM treats a large and diverse population, including women, pediatric, geriatric, and patients of color, and has the potential to promote diversity in clinical trials, recruiting patients for participation in EM clinical trials appears to be very challenging.Compared to OB/GYN and ID patients, EM and FM patients did not indicate strong motivation to participate in clinical trials by the factors listed in our survey. It is noteworthy that since the survey was offered to all patients in the waiting rooms of each specialty, the survey was consequently not offered to those EM patients who arrived by ambulance. Other patients who were not surveyed might have included those whose condition was so severe that they were taken directly to a bed without any wait. However, had we included these patients, it is possible that the motivational factor scores for EM may have been even lower because of the physical and psychological stressors associated with these patients’ severe health conditions.Based on median scores, ID and OB/GYN patients ranked a total of four out of the 10 motivational factors as very highly motivating, while FM patients ranked three, and EM patients ranked only two factors as very highly motivating. For EM patients, scores for motivating factors were lower, and scores for most barriers were equal to other specialties. These findings help explain the challenges EM investigators and research staff experience and struggle with when trying to enroll patients in EM-based clinical trials.It perhaps is not surprising that differences exist among the various specialties in their perceptions of factors that both motivate and deter patients from participating in clinical trials. In fact, EM patients are less likely to be influenced by the doctor’s reputation or their relationship with their physician. This is in contrast to prior studies that have generally described an established relationship with the investigating physician as a strong motivator in making medical decisions, including clinical research participation.The motivation for all patients, including EM, appeared to be the least affected by the investigator’s race, their desire to please the doctor, financial compensation, and the investigator’s gender (with the exception of OB/GYN patients). The factor “knowledge gained will benefit someone in the future” was ranked highly by all specialties. Altruism is widely reported to be a motivating factor for research participation,18The primary barrier to participation for all specialties, including EM, is “fear of unknown side effects.” This finding is in concordance with other reports.Factors that are easily modifiable by investigators, such as the provision of written or electronic material, were rated as moderately helpful in recruiting for clinical research. This was true even for the provision of material in the patient’s own language. Compared to other specialties, EM had more respondents who belonged to a Latino or Hispanic origin, had less than a college-level education, and had fewer participants who were fluent in English. A prior study regarding enrollment challenges in EM research reported that a sizable proportion of eligible, non-English-speaking Latinos were not enrolled due to language barriers.As the time frame to consent patients in the ED is usually shorter than for other specialties,30Since demographic variables, such as patient’s gender,Our hypothesis that the impact of factors influencing a patient’s decision to participate in clinical trials may vary among specialties was tested and confirmed by logistic regression analyses of a few of those factors that were significantly different for EM from either all, or a majority of other specialties in our sample. Regardless of their gender, race, and education status, “relationship with their doctor” was least motivating to EM patients than those from FM, ID, and OB/GYN. This finding as discussed above is logical. Patients and emergency physicians usually see each other only one time, and the chance of them seeing each other again in the future is slim to none. Additionally, EM patients have no choice of selecting their own doctor, whereas in other specialties, patients routinely make appointments with their preferred doctor for their follow-up care.The results were similar for the barrier of “time commitment.” Regardless of patient’s race, “time commitment” was considered less of a barrier to EM patients, males, and those with less than a high school diploma. As the majority of EM patients present with acute and often-undifferentiated illnesses, it is logical that for them the diagnosis and resolution of emergency take priority over time commitment. Regression analysis of a second barrier, “my religious beliefs,” which was scored significantly differently by EM patients than two other specialties (FM and ID), was found to be influenced by factors other than the specialty.The results confirm our hypothesis and show that, regardless of demographic characteristics, the impact of some influential factors does vary from one specialty to the other. Therefore, we recommend that researchers customize their recruitment approach according to their specialty.To our knowledge, this is the first large-scale prospective study that investigated factors that influence EM patients’ decision to participate in clinical trials. This is also the first one indicating that the impact of the same factor may vary from one specialty to another. The strengths of this study include its large number of patients and an excellent response rate. Also, the availability of multilingual research staff and translated surveys in Spanish, simplified Chinese, and traditional Chinese maximized diversity.Although surveying previous clinical trial participants and those who declined to participate in previous clinical trials may have been a better option for investigating influential motivators and barriers, human research participant protection and confidentiality-related policies did not allow us to identify and survey this population. The current study used a convenience sampling method based on when the research staff was available and on the patients who happened to visit the office that day, rather than a random-selection method. In addition, all participants were approached in the waiting room of these specialties. Since ambulance patients were excluded, our findings do not represent this subgroup of ED patients.We acknowledge that although the overall response rate was satisfactory, a non-response bias may have potentially swayed the results. However, the reason(s) for non-participation were not collected, and IRB restrictions did not permit collecting demographics on non-participants. Therefore, a non-response bias analysis was not possible. Further, the decision to participate in a clinical trial depends on a variety of factors, and it is possible that a clinical trial has other motivators and barriers that were not assessed in this study. We acknowledge our survey responses may not mimic actual responses of potential subjects to a legitimate research trial invitation.Even though a patient’s decision to participate in clinical trials depends on multiple factors, we conclude that the impact of the same factor may vary from one specialty to another. Researchers should focus on factors that are more influential to their specialty populations and should customize study designs to make clinical trials more appealing to potential participants. When considering participation in clinical research, EM patients ranked their relationship with the doctor and the importance of their physician’s reputation as significantly less important than patients in other specialties. The fear of unknown side effects was the most significant barrier for patients of all specialties. Although compared to other selected specialties, EM patients appeared to be less motivated on most factors assessed, providing material in a patient’s own language, explaining the study well, and elucidating how their participation might benefit others in the future, may improve enrollment in EM-based clinical trials.


The American anti-mosquito movement grew out of the discovery of the role of mosquitoes in transferring pathogens and public concern about pest and nuisance mosquitoes in the late 1800s. In the 20th century, organized mosquito control in the United States passed through three eras: mechanical, chemical, and integrated mosquito control. Mosquito control in the 21st century faces the challenge of emerging pathogens, invasive mosquito species, and balancing concerns about the environment with effective control strategies. This review is drawn from Gordon M. Patterson’s Mosquito Wars (University Presses of Florida 2004)  and The In October 1770, Johann Wolfgang von Goethe, who would later become Germany’s most famous poet, writer and statesman, made an excursion to a village on the Rhine called Sesenheim. There, the 21-year-old von Goethe, who was studying law in nearby Strassbourg, met and fell in love with Frederike Brion, the daughter of the town’s Protestant minister. A brief, intense love affair ensued. One afternoon during an excursion a brood of “entsetzichen Rheinschnaken” (horrible Rhine mosquitoes) drove the young lovers back to Sesenheim. Later, von Goethe declared to Frederike’s father that the existence of mosquitoes made him doubt God’s goodness. How, von Goethe wondered, could an “omniscient, omnipotent, and benevolent” Deity have blighted creation with mosquitoes? The virtuous parson disagreed explaining that in the Garden of Eden mosquitoes were gentle, pacific creatures. It was only “after the fall of our first parents” that mosquitoes came to prey on human beings. Von Goethe retorted that it surely must have been mosquitoes and not an “angel with a flaming sword” that had driven “the sinful couple” from paradise  (p. 533)Micrographia, or Some Physiological Descriptions of Minute Bodies made by Magnifying Glasses. Improvements in the compound microscope which was invented in the 16th century gave Hooke, John Swammerdamm, and most notably Jean Rèaumur unprecedented insight into the world of insects. In 1738, Rèaumur devoted his fourth memoir, Histoire des Cousins, to describing the life history of Culex pipiens. Unlike von Goethe, Rèaumur believed that no part of God’s creation was unworthy of admiration. Today, Rèaumur would be called an ecologist. He believed that each living thing is connected to all of the other living things that surrounded it. Rèaumur opened a new chapter in the history of entomology. His accounts of the life histories of insects are striking for their detail and clarity. Nowhere is this more clearly shown than in his discussion of mosquitoes. Rèaumur wrote:Von Goethe was unaware that, at that very moment, a revolution in human understanding of the insect world in general and mosquitoes in particular was underway. A century before von Goethe’s musings, Robert Hooke (1665) offered a detailed description of mosquitoes in his “I have received written observations on various insects, and particularly on mosquitoes, from a learned Chartreux [monk] who amuses himself and busies himself admiring the works of the Almighty wherever he isn’t occupied in singing His praises. He has studied mosquitoes more and longer than the authors who have written about them. Not only has he found that their worms leave skins behind them but he is satisfied that they leave three of them aside from the last to which are followed by changes in the insect’s form. If all these pious monks—had a penchant for observing insects, we might expect that the most essential points in the life history of these little animals would soon be made known. What diversion could these monks propose more worthy of the life they have embraced than the one which would place under their eyes the marvelous creations of a Power unlimited? For therein, even their leisure would give them more occasions to adore Him than have those [other monks] who are diverted from Him by too many occupations, whether serious or frivolous  (p. 8).”Memoires pour servir a l’Histoire des Insectes provides insight into his fascination with mosquito anatomy and physiology. Most striking is the mixture of respect and admiration with which he speaks of mosquitoes. He wrote:Reading Rèaumur’s “Mosquitoes are certainly our declared enemies, and very annoying enemies at that. But they are enemies good for us to know. If we give them even the least bit of attention we find ourselves forced to admire them and to admire even the instrument they bleed us with; for this it is only necessary to examine their structure. Furthermore, throughout their lives they offer facts adequate to please any of those minds which are curious about the marvels of nature. There are even times in the mosquitoes’ lives when, having made the observer forget that they’ll persecute him some day, they make him feel actually, solicitous about their welfare”  (p. 7).Few have written with greater eloquence and sensitivity about mosquitoes.Rèaumur’s sympathy for mosquitoes, however, did have limits. Like von Goethe, he reported that he encountered peasants in the country side with such severe mosquito bites on their arms and legs that he feared amputation might be necessary. Horror stories about mosquitoes in the 18th and early 19th century abounded. In 1736, the people of Salisbury, England, were terrified by “vast columns” of mosquitoes which darkened the skies above the city’s famous cathedral. Many mistook the brood of mosquitoes for smoke and thought that the cathedral was on fire. Twenty years later another sinister “black cloud” of mosquitoes descended on Oxford…almost totally intercepting the beams of light”  , and John Smith, a professor of entomology at Rutgers University. Four years later, Smith published his ground breaking arvicide . In 1912Smith’s work proved a model for advocates of mosquito control in California in 1905. Citizens in Burlingame and San Mateo requested help from the entomology department at the University of California in finding relief from salt marsh mosquitoes. Four years later, a young Ohio entomologist named William Herms joined the Berkeley faculty. Herms had little interest in pest and nuisance mosquitoes. In 1910, he began California’s first campaign to control anopheline mosquitoes in Penryn, California. A year later he sought to win state approval for an abatement act to control pathogen-bearing mosquitos. Herms failed twice (1911 and 1913) in his effort to secure a law allowing counties to organize mosquito control districts. In 1915 California authorized the formation of abatement districts when Herms won the support of the powerful real estate lobby which feared mosquitoes in certain areas would adversely affect property values.Ae. aegypti control program, was spared. In December 1922, 100 proponents for mosquito control met in Daytona, Florida, and formed the Florida Anti-Mosquito Association. They chose Joseph Porter, who had served as the state’s first health officer, as their inaugural president. The closing words of Porter’s presidential address were to become the mantra for mosquito control workers in Florida and across the nation. Porter declared, “Keep everlastingly at it”  drainage program alone is not expected to have great permanent value, however, unless it is followed by continued maintenance”  (p. 80).The CWA pest mosquito project presented an even more daunting challenge. Like Williams, Fred Bishopp was under orders to get men to work on mosquito control projects immediately. The malaria work was limited to 14 southern states where the USPHS had extensive experience since 1912. The CWA pest work stretched from New York to California. Many states lacked any experience with mosquito control. Bishopp, however, remained optimistic. He was adamant that “mosquito control work is one activity which has been promoted rather than handicapped by the depression”  (p. 37).In 1937 the Audubon Society attacked mosquito control. “The zeal for drainage”, WilliamVogt wrote, “has ravaged the North American continent like some form of terrestrial erysipelas. Wildlife and vegetation have been killed, and the earth has dried up”. The federal emergency support of malaria and pest mosquito control ditching was but the most recent assault on the nation’s water resources. Vogt argued that the federal mosquito control work was a “publicly financed sales talk…that under the guise of ‘education’ officials concerned with mosquito control have made sweeping claims without producing any scientific proof”. Citing the work of Clarence Cottam, Warren Bourne, and F.M. Uhler at the USDA’s Biological Survey, Vogt charged the CWA, CCC, and WPA sponsored malaria and pest mosquito control initiative was no more than a “government-sponsored racket” ”, Eldridge argued, “saw the eradication of the Aedes aegypti mosquito…as a pressing health concern”. The CDC’s leadership believed that “the decision to eradicate the Aedes aegypti mosquito was a political one, a matter of foreign policy  to conduct broad advocacy research”. The report concluded: “It is not the intent of the Florida Medical Entomology Laboratory staff to embarrass any of the foregoing gentlemen but to demonstrate that the administrators of social programs or pursuers of limited objectives are inadequate for administering research. Nothing would be solved by the appointment of new administrators as their outlook could be little different.” Maurice Provost’s standing as an internationally renowned researcher had served to shield the laboratory from meddlesome bureaucrats. “Since Dr. Provost’s death”, the staff members declared, “only pending legislative bills to transfer FMEL to the University system have restrained hands that would reshape the reputation of the FMEL  (p. 6).”Critics of mosquito control have long claimed that the impounding of coastal salt marshes had damaged environmentally sensitive wetlands. In Florida, the management of these impoundments underwent significant improvement in the 1980s. In 1982, the U.S. Department of Commerce launched an eight year study of Coastal Zone Management (CZM) practices. In Florida, Jorge Rey (FMEL), Grant Gilmore (Harbor Branch Oceanographic Institution) and Doug Carlson (Indian River County Mosquito Control District) authored a detailed analysis of the of the effects of different water management strategies on coastal salt marshes . They coBacillus thuringiensis var. israelensis (Bti) as a larvicide. The success of Bti led researchers to explore other bacterial agents. In the mid-1980s, Mir Mulla at the University of California, Riverside and others identified the efficacy of Bacillus sphaericus as a control agent  overseeing the field sites.” .Finally, there have been significant advances in research on mosquito repellents. In the 60 years since the discovery of DEET, researchers have sharpened their understanding of mosquitoes’ olfactory system . At the Aedes. aegypti mosquitoes are the prime vector of both of these flaviviruses. There is as of yet no effective vaccine for either disease. Mosquito control and, in the case of Zika the practice of safe sex, remain the only means to break the transmission of these viruses. Unfortunately, though mosquito control has proven its effectiveness against many pest and pathogen-bearing mosquitoes, the recent experience with Zika has demonstrated that breaking the transmission cycle of mosquito-borne pathogens during an Ae. aegypti-borne epidemic remains at best problematical. Research on topics to improve mosquito control effectiveness continue with the development of new strategies for control including chemical, biological, genetically modified organisms, repellents, attractants for trapping and many more. History shows us that progress in mosquito control is dependent on the research efforts of dedicated scientists and mosquito control professionals.The development of mosquito control in the 21st century will in large measure be determined by the success of control efforts in facing the challenge posed by the resurgence of dengue fever and the appearance of Zika virus on the world stage. Von Goethe’s contemporary, Georg Wilhelm Friedrich Hegel, once observed that “the only thing people have learned from history, is that no one ever learned anything from studying history”. The history of mosquito control and medical entomology provides some measure of optimism in the face of Hegel’s pessimism. Much has been learned about mosquitoes since von Goethe and Frederike’s encounter with the “entsetzlichen Rheinschnaken”. The research efforts of countless medical entomologists have deepened our understanding of the role of mosquitoes in transmitting pathogens that cause human diseases. If there is a lesson in the history of mosquito control, it is that there are no “magic bullets”. Protecting the public from pathogen bearing and nuisance mosquitoes depends on research to improve mosquito control and an abiding respect for the environment. When at its best, mosquito control is applied ecology.


Dysbiosis is a key term in human microbiome research, especially when microbiome patterns are associated with disease states. Although some questions have been raised about how this term is applied, its use continues undiminished in the literature. We investigate the ways in which microbiome researchers discuss dysbiosis and then assess the impact of different concepts of dysbiosis on microbiome research. After an overview of the term’s historical roots, we conduct quantitative and qualitative analyses of a large selection of contemporary dysbiosis statements. We categorize both short definitions and longer conceptual statements about dysbiosis. Further analysis allows us to identify the problematic implications of how dysbiosis is used, particularly with regard to causal hypotheses and normal-abnormal distinctions. We suggest that researchers should reflect carefully on the ways in which they discuss dysbiosis, in order for the field to continue to develop greater predictive scope and explanatory depth. As microbiome research has flourished, so has the use of the term “dysbiosis.” Particularly when patterns in microbiota are linked to human health and disease states, dysbiosis is often invoked as a state that mediates these associations. Although a few commentators have noted the looseness of what dysbiosis means and is doing scientifically  (emphasis added) . The first microbiological use of this term appears in C. Arthur Scheunert’s 1920 paper on the relationship between intestinal “flora” and bone inflammation in horses . He clais added) .We suggest that although these three authors provide very different resources for thinking about dysbiosis, their contributions nevertheless ended up being combined historically: Metchnikoff urged scientists to think about normal and abnormal microorganismal effects on hosts, Furney promoted the words dysbiosis and eubiosis but gave them a rather dubious fictional context, and Scheunert brought together the terminology and relevant microbe-host research .Regardless of the precise details of the older history, the revival of dysbiosis in scientific literature in English occurred via the prolific work of Helmut Haenel, a “microecologist” of the postwar era in Potsdam, Germany  for the word dysbiosis. However, very little of this recent literature tries to be more elaborate or precise when discussing dysbiosis than Haenel and other 1970s writers were. Despite this, the term seems more concrete now than it has ever been, and it is not clear that this is justified. To find out more about contemporary uses of dysbiosis, we systematically investigated today’s microbiome literature.Clostridium difficile infections, and autoimmune disorders.Our analysis focused on over 9,000 PubMed abstracts in which the MeSH term “microbiota” appears , along with families, orders, and classes. Finally, about 1 in 12 definitions did not fit our categorization scheme  compared to the semi-automated analysis of the 554 abstracts. This is probably because we discarded large numbers of texts from our long-definition search due to the papers having no definition at all  or having only an extremely abbreviated definition .A few articles from our publication sources for 100 long definitions summarize different meanings of dysbiosis see also . For exa10.1128/mBio.01492-17.4TABLE S3 TABLE S3, PDF file, 0.1 MB.List of long additional definitions. Download Copyright © 2017 Hooks and O’Malley.2017Hooks and O’MalleyCreative Commons Attribution 4.0 International license.This content is distributed under the terms of the In addition, Vangay et al.  construcAs microbiome research attempts to become more explanatory, a few authors have begun to question the concept of dysbiosis. Olesen and Alm  provide Broad catchall definitions are not normally esteemed in scientific practice. Too many cases fall under such terms, and they cannot thus discriminate between different and potentially meaningful situations. Due to the known variability between the microbiota of any human and those of others, and limited samples of healthy and ill hosts, dysbiosis is easy to find. The broader the definition, the more easily it is detected. We certainly found dysbiosis identified by this means, and it was not uncommon for any change in microbiota composition to be the main finding of the microbiome analysis as long as it was associated with illness. Some papers attempt to be more discriminatory by limiting dysbiosis to major changes. For example, Antharam et al.  classifyMany of our 100 long definitions specify that for the altered microbiota to be considered dysbiotic, the changed state would need to have a negative effect on the host. Representing this position, Petersen and Round  state thThere are some basic problems with such broad illness-linked accounts of dysbiosis. One, as Olesen and Alm  argue, iBut more generally, there is an overarching methodological problem in these attributions of dysbiosis: by searching for microbiota change in ill people, the dysbiotic state is circularly confirmed as conferring illness. As Bäckhed et al.  observe,When microbiome researchers invoke dysbiosis, they can be implying two different scenarios: one in which dysbiosis is reliably coproduced by whatever causes the disease (or by the disease itself), and another in which dysbiosis itself is a major causal factor in producing the disease. If the first holds, dysbiosis is at most diagnostic. If the latter, dysbiosis is explaining the disease. The identification of dysbiosis could, therefore, lead directly to effective treatment. Both diagnostic and explanatory uses of dysbiosis are common, sometimes in the same definition: for example, “an imbalance in the microbiota composition and a shift in their function from normal to disease”  and “altThere is broad consensus in microbiota research that the field needs to move beyond associations to more exact causal factors. Associations may deliver hypotheses about causal relationships, which means that the former are a valuable initial source of insight for explanation and intervention. However, when dysbiosis is invoked as something substantive, it may produce the impression that the mechanism of the disease itself has been discovered. So far, mechanistic discoveries have been few and far between in microbiome research. Assertions of “dysbiosis” tend to function as placeholders, by indicating that microbiome results may be relevant to the illness. Although compositional change may be conceived as a “mechanism,” mechanisms usually need to be more specific and manipulable in order to be testable. It is finding out more precisely the explanatory “place” that dysbiosis is holding that is the ultimate aim of health-related microbiome inquiry.But if mechanisms of disease are desirable, is taxonomic composition the right focus? Should it be physiological function? Microbiota are not efficiently designed physiological machines. They assemble both stochastically and deterministically. The latter assembly is dictated by environment, including host selection processes. Selection is unlikely to be targeting taxa; it works on traits such as function. Because of this, dysbiosis and nondysbiosis are probably more effectively understood in functional terms , 31. TheAlthough focused mechanistic understandings of host-microbiota interactions will probably depend on both taxonomic and functional analyses of microbiomes, extracting mechanisms from dysbiosis findings is not going to be easy—particularly if culturing is required to understand how pathways bring about particular effects. What may help in streamlining this transition is a better understanding of nondysbiosis. Because any account of dysbiosis relies conceptually on the positive state being disturbed, this has implications for how mechanisms and explanations might emerge from microbiota research.Clostridium difficile infections.Homeostasis is the front-runner term in microbiota research for the desired nondysbiotic state. Classically, homeostasis implies a dynamic process that has mechanisms to return the system to a balanced state after perturbation e.g., . It is eFollowing this ecological line of thinking, ideas about stability—a key theoretical concept in ecology—may be relevant when the positive “balanced” or “homeostatic” state of the microbiota is being discussed , 40. DivC. difficile patients “cures” them, the success of such transfers probably lies in very narrow functional groups  rely on the idea of a normal healthy microbiome and microbiota. The homeostasis concept implies an explanation of this dynamic normal state, but it is seldom provided; eubiosis and normobiosis are usually intended as static descriptive terms, which is where most unelaborated uses of homeostasis fit. The question that all three terms raise, therefore, is how “normality” is defined and detected.Earlier intestinal microbiologists believed that quantifying microbiota differences would reveal what causes dysbiosis. They therefore made efforts to calculate “normal” microflora statistically e.g.,  and 59. In general, because microbiota indices are not constructed on the basis of time-series data, they cannot capture responses to perturbation—the very phenomenon that dysbiosis attempts to describe. Moreover, even the best indexing efforts with larger samples e.g.,  are tiedA number of the papers that we analyzed raised concerns about dysbiosis and the conceptual role that it plays in microbiome analyses e.g., . Many mo63 to Continued use of the term dysbiosis can be understood in two ways: as a part of scientific analysis (thus requiring more rigor) or as a broad communication tool . Problems arise when these two ways of using language are conflated. Our overview suggests that this may be happening more often than not. As a broad descriptive placeholder , dysbiosis works like a flag for future work. But if a loose description like this is viewed as the concluding finding in its own right, then more fine-grained discovery may be preempted.The historical legacy of dysbiosis is interesting here. Already in the 1960s and 1970s, intestinal microorganism researchers such as Haenel saw the need to quantify claims about dysbiosis and eubiosis in disease . Despite