Uspekhi Mat. Nauk.XIII, 3–72. (Russian).), it is well known that the set of partial indices of a non-singular matrix function may change depending on the properties of the original matrix. More precisely, it was shown that if the difference between the largest and the smallest partial indices is larger than unity then, in any neighbourhood of the original matrix function, there exists another matrix function possessing a different set of partial indices. As a result, the factorization of matrix functions, being an extremely difficult process itself even in the case of the canonical factorization, remains unresolvable or even questionable in the case of a non-stable set of partial indices. Such a situation, in turn, has became an unavoidable obstacle to the application of the factorization technique. This paper sets out to answer a less ambitious question than that of effective factorizing matrix functions with non-stable sets of partial indices, and instead focuses on determining the conditions which, when having known factorization of the limiting matrix function, allow to construct another family of matrix functions with the same origin that preserves the non-stable partial indices and is close to the original set of the matrix functions.From the classic work of Gohberg & Krein (1958  It is also referred to as right continuous factorization. If we have the representationleft (or left-sided) factorization. If the right- (or left-) factorization exists, then the integers partial indices, are determined uniquely up to their order, e.g. G−, G+ are not unique  has a stable set of partial indices if there exists δ>0 such that any matrix function F(x) from the δ-neighbourhood of G(x) (i.e. ∥F−G∥<δ) has the same set of partial indices (right or left). If not, then G(x) has an unstable set of partial indices. It has been shown  own  that a G(x) can lead to changes in the partial indices. More precisely, there exists a sequence of matrix functions Fk(x) that converge to G(x), but which has a distinct set of partial indices, i.e.ΛA(x)≠Λ(x).In the unstable case, a small deformation of the matrix function do not possess limiting values (as G(x). On the contrary, even in the case of unstable partial indices, we can easily construct a sequence of factors ΛA(x)=Λ(x). Indeed, in a simple example we present the pair G∓, such that We note that, in all the known examples illustrating such a situation e.g. ,6), the , the 6])k+(x) in  with theperturbation of the matrix G.Let us now consider a family of matrix functions Gε is considered ‘regular’, if there exists ε0>0 such that the matrix Gε possesses a bounded factorization  and z∈Π±). Otherwise the perturbation is considered ‘singular’.Let Gε are the same as those of G.The partial indices of the regular perturbation Gε be a regular perturbation of G(x),ε→+0, we obtain ΛA=Λ due to the uniqueness of the partial indices. ▪LetG satisfy the condition G is regular.If the partial indices of Λ(x)=G0(x) and the partial indices G0(x):ε>0, the matrices are close to each other, such thatε>0, the matrix Gε(x) possesses the following factorization with partial indices ε>0, the factors in this factorization admit analytic continuations into the corresponding half-plane, where they are bounded. However, these factors are not uniformly bounded for ε∈[0,ε0) for any ε0>0. Hence Gε(x) is a singular perturbation of the above diagonal matrix G0(x) .This example provides a simple, but not unique, method for the construction of the singular perturbation x)G0+(x) ,1.9Gε(sGε(x) be a perturbation of a factorizable matrix function G0(x). If there exists another perturbation k-guided perturbation’ of Gε.Let Gε(x) of the matrix function G0(x), there exists a singular k-guided perturbation k≥1.It follows from  that fora, we show that for any factorizable matrix G0(x), with a stable set of partial indices, there is a ε-neighbourhood containing only regular perturbations. Figure 1b illustrates the case of unstable partial indices of G0(x). Here, the situation is more delicate, as we can see that in each ε-neighbourhood of G0(x) we can find either regular or singular perturbations.The above-mentioned properties are illustrated in figure 1k-guided (k>1) perturbation Gε(x) of the matrix function G0(x). Perturbation Gε(x) is of the same type as in [G0(x) has a known factorization with unstable partial indices. For k=1, this is trivial but has no practical use.The aim of this paper is to consider the construction of a regular pe as in ,10, and k-guided perturbation helps us to highlight possible structure of the set of partial indices of those matrices locating in ε-neighbourhood of a matrix with unstable partial indices. Clearly, with the higher k-guided perturbation is possible to construct the more accurate approximation of the original set it creates.The notion of The factorization technique is a powerful tool in solving practical problems –18, and n×n matrix function Gε(x) of the matrix function G0(x), and possessing an unstable set of partial indices. More exactly, we ask when it is possible to find Gε(x)? To reach an answer to this question in the case of unstable partial indices, a new definition of the asymptotic factorization is given and applied. The method, as proposed in [Below, we discuss whether, and under which conditions, it is possible to find an posed in ,10, is gsolvability conditions for a certain boundary value problem. We also provide examples where the solvability conditions are satisfied and unsatisfied. We conclude with illustrations of the obtained numerical results and a discussion of their importance in §The paper is organized as follows: In §2.μ:invertible matrices. It should be noted that our method can be also be applied to a wider class of matrix functions, e.g. having no prescribed modulus of continuity.To proceed, we make some necessary definitions. We denote by Below, we give a definition of the asymptotic factorization only in the case of the regular perturbation of a given matrix function, since we lack for the moment a formal procedure which distinguishes between the cases of regular and singular perturbations and as yet have no useful example of the construction of the asymptotic factorization of a singularly perturbed matrix function.Gε(x) be its regular perturbation. We say that a set of pairs of matrix functions, m=1,2,…N), and a diagonal matrix ΛA(x) of the form (θk(ε), k=1,2,…N+1, that vanishes at the point ε=0, such that for any k=1,2,…,N(i) there exists a sequence of functions (ii) there exist matrices ε0>0 such that the matrices Π∓, respectively, and bounded in ε∈[0,ε0),(iii) there exists m=1,2,…,N(iv) the following estimate is valid for any Let the form  represenN) of the matrix Gε(x).The representationθk(ε)=εk.We note that conditions  and 2.32.3 guara side of  represen side of , we coulregular perturbations of the given matrix, i.e. we are looking for representations =Λ(x). However, even in this case, no uniqueness can be guaranteed.— The method used in , in the ε≥0.— The factors entation  are contΛA(x)=Λ(x)).— Although the asymptotic factorization is not unique, we can prove, similarly to lemma N>1 exists, then the matrix functionN+1)-guided perturbation of the following perturbation Gε(x) of the matrix G(x):— If an asymptotic factorization of order Some clarifications are required for this definition:Γ which divides the complex plane into two domains D− and D+, by changing the diagonal entries in Λ(x) to t∓∈D∓, or simply to D+.Although we only consider in this paper the factorization of a matrix function on the real axis, we can tackle in the same way the factorization of matrices defined on any oriented curve ε such thatLet us now consider a matrix function rization , with unOur motivating question is the following: how to distinguish a class of possible perturbations that allows constructing an asymptotic procedure described in –2.5). I. I2.5). 3.θ1(ε)=o(1) as ε→0 and Nε is bounded and Hölder continuous on ε=0, the matrix G0(x) possesses a factorization with unstable partial indices  of the type (G0(x), up to some stage of the asymptotic procedure. For simplicity, we will consider θk(ε)=εk Gε(x) in the following form:Π∓, together with their inverses, and bounded in First, we present the matrix ε, we arrive at the following boundary condition for Comparing the term with parameter Π− and Π+, an bounded in In order to determine solvability conditions for this problem and to find a representation for the solution, we present here a few facts from the theory of boundary value problems ,24. It iintegral , p. 523formal solution to , but not all the solvability conditions are satisfied by the proper choice of Representation , and furution to  has the  problem , with fafined by , if and (b)k,q+1≤k≤n, we have z=−i follows whenever we choose — if for certain k,q+1≤k≤n, we have mlk0,(τ) have to satisfy conditions— if for certain en as in , and thek,1≤k≤p, we have z=i follows whenever we choose — if for certain k,1≤k≤p, we have mkj0,(τ) have to satisfy conditions— if for certain en as in , and thel,j) is such that 1≤l≤p,q+1≤j≤n, then additional solvability conditions must satisfy— if the pair  is such that either 1≤l≤n,1≤j≤q, or p+1≤l≤n,1≤j≤n, then we have no condition on the entries mlj0,(τ); the corresponding constants — if the pair   Formula ,  and  are satiz=−i, z=i, respectively. By choosing sufficiently small ε1>0, we can guarantee that the matrix functions ε∈[0,ε1), formula n constants np constants n−q)p cases described in  constants — The numbers of solvability conditions and conditions on the choice of the constants satisfy the following relations.Gε(x) be a perturbation of G0(x). Then, in particular, Gε(x) is in the ε-neighbourhood of G0(x) (a). If the matrix Gε(x) satisfies the above solvability conditions, then there exists for all sufficiently small ε the matrixG0(x). The matrix ε2-neighbourhood of Gε(x) (b). This means that for each point of linear manifold of the matrices Gε(x), as defined by  a. If theof Gε(x) b. This mfined by , which s(c)rth step of the factorization using the representationformal solution to problem  with the functions mr−1,ij(x), and the constants Let the solvability conditions be satisfied and the constants nditions –3.16) a acij0 chr=N+1, at least one solvability condition fails, then the procedure for the asymptotic factorization is stopped at this point.If at a certain step Gε(x) be a regular perturbation of G0(x). In particular, (as for N=1) Gε(x) is in the ε-neighbourhood of G0(x). If the matrix function Gε(x) satisfies the above solvability conditions at each step r,1≤r≤N, then for all sufficiently small ε there exists a matrixG0(x). The matrix εN+1-neighbourhood of Gε(x). This means that for each point of linear manifold of the matrices Gε(x) that satisfies the solvability conditions, there exists an (N+1)-guided perturbation. Thus, with a larger number of steps we can proceed in our approximate factorization more closely to the index-preserving approximation to a given matrix Gε(x).In this case, we summarize the situation as follows. Let the matrix function Nth step of the approximation, then we can only construct an approximate factorization up to the order N−1. If a solvability condition fails at the first step of the approximation, then we do not have a tool to construct a regular k-guided perturbation for any k>1.If at least one solvability condition fails at the (d)Gε(x) of the formG0(x). Here the matrix function G0(x) is given by (We apply the above-described asymptotic procedure to the matrix function given by .Gε(x) can be represented in the following form:Λ(x) is the same as in remark Nε(x) is given byGε(x) can be thought of as a small perturbation of the matrix function G0(x)=Λ(x) (Nε(x) takes the following representation (uniform in ε) on any finite interval:The matrix function ϕ has the following properties (cf. [θ1(ε)=O(ε). We can thus later use an artificial small parameter ε instead of θ1(ε).The introduced small parameter ies  at infinity (θ1(ε) with respect to ε. If, for example, θ1(ε)=O(ε1/2).In fact, the first-order decay of infinity  is cruciThe first step of the asymptotic factorization procedure.ε1, of the functional equationMε0,(x)=Nε(x).We look for a pair of matrix functions )=I  given by  is given by the following formula:Thus, the first-order approximation ented in  and =O(ε2) as ε→+0 and thus Gε(x).In order to estimate the quality of the approximation, it is customary to define the following remainder matrix:ΔKε1,(x) has an interesting behaviour, as a consequence of a special property of the matrix Nε(x): n11=−n22. Namely, it tends to the diagonal matrix as Matrix ΔKε1,(x) of the first-order approximate factorization of the matrix Gε(x) can lead to a violation of the solvability conditions for the corresponding boundary value problem. Let us considerSimple changes to the matrix We note thatWe apply the above-described asymptotic procedure to our matrix The corresponding matrix is given byThe first step of the asymptotic factorization leads to the problemBounded solutions to  have to ε=0. For all ε≠0, there is no approximate solution (up to ε2) of the functional equation .k-guided perturbation (k>1) exists while construction of a singular perturbation remains an open problem.Note that, by construction,4.In this section, we analyse the quality of the approximation provided by the 2-guided perturbation performed in §3d.c21=0, and thus the limiting value of the remainder, ΔKε1 does not vanish at infinity. Specifically, we estimate the element on the main diagonal in the following way:First, we consider the case when a,b, those components are presented in their normalized forms. We can see that the estimate is true . Furthea,b, the remaining two components are depicted in the same normalized forms. Preserving the same estimate, where ΔKε1,(x)=O(ε2) as ε→0, the components now decay to O(x−1), as ε is, the slower it converges to its limiting value. In other words, the small parameter ε determines the magnitude of the reminder matrix, but the oscillations are larger in this case, and more pronounced along the real axis.In figure 3Interestingly, the components on the main diagonal are comparable in value, but not equal, while the remaining two differ in value by almost a factor of two. Moreover, the latter are also two times smaller in magnitude than the diagonal elements.O(x−1), as O(ε2)) when ε→0, as predicted. The magnitudes of the components are, however, more balanced in the sup norm c21. Comparing these two cases, it is clear that the second is preferable to the first for the reasons discussed earlier.The situation changes when we consider the second case, where Any specific factorization will of course require its own analyses. However, if the estimatecjl (first step) and djl (second step), j,l=1,2.We note that this property may change in the next step if we wish to and can continue the approximation procedure . Here, the limiting values for the first step will also play their role. We can deliver a similar formula based on the two consequent approximations, where two sets of constants will then be involved: Judging by the magnitude of the reminder for both the presented examples, we can conclude that the 2-guided perturbation may be sufficient for practical purposes. Thus, if even one approximation step is practically possible, meaning that conditions –3.16) a a3.16) aGε, with unstable partial indices, are not satisfied, the question of how to compute a valuable approximate factorization for such a matrix-function remains open.To close, we must highlight that, if conditions –3.16) f f3.16) f


Rural and remote places like Sable Island (Nova Scotia) or François (Newfoundland) pose a challenge in delivering both health care and appropriate education that today’s learners need to practice in a rural setting. This education can be difficult to deliver to students far from academic centers. This is especially true for learners and practitioners at offshore locations like ships, oil installations, or in the air when patients are transported via fixed wing aircraft or helicopter. The following editorial provides a snapshot of the setting and the challenges faced while working as a physician on a ship, in remote regions. Akademik Ioffe, the ship that held my heart for 15 years since I was last her doctor in Antarctica. Soon she will take me along with 102 passengers to beautiful, rural but remote places like Sable Island (Nova Scotia) and François (Newfoundland). Both places are magical to visit, but in the longer term, they provide us with a challenge in terms of delivering both health care and the necessary education for today’s learners to practice in a rural setting. Unlike seasoned physicians, newer students may rely more upon sophisticated technology for diagnosis and treatment, which is rarely found in rural and remote areas. As the ship’s doctor, I hope this voyage does not present the kinds of clinical challenges that characterize practice in faraway places. If somebody gets sick aboard ship or is injured in François where there is no road, it is a far different proposition to care for them than in the academic emergency room, where I normally work.I write this editorial from the Delivering rural and remote health professions education (HPE) is similarly challenging. The mission statement of the medical school at Memorial University of Newfoundland (MUN) states that students should receive the same quality of education no matter where in the province they are learning. In reality, this can be difficult for students who are far from an academic center. This is particularly true for learners and practitioners at offshore locations like ships and oil installations and in the air when patients are transported via fixed wing aircraft or helicopter. The challenges vary tremendously, from communicating effectively , throughFinally, we are underway, and my thoughts return to the journey. The heavy anticipation and wait for departure lift as I feel the bow thrusters pushing us away from the Halifax pier. The ship’s crew is relieved to be moving too, for being in motion defines the voyage.coup de grâce to the Zodiac’s pontoon. For more mundane emergencies, I carry a variety of supplies and a defibrillator and remain in constant radio contact with the crew and the bridge.I have already checked the infirmary’s supplies . The crew is replenishing ship supplies while her navigator is charting a course for Iqaluit, the starting point for the next voyage: through the North West Passage and eventually to Greenland. Another ship’s doctor will replace me and keep watch over another 100 or so passengers. They will sail to iconically beautiful and remote places and perhaps encounter medical emergencies. May fair winds prevail!The


Tens of millions of children regularly participate in out-of-school-time (OST) programs, providing an opportunity for child health promotion. Most research on OST has focused on structured, staff-led after-school programs, as opposed to volunteer-led programs such as enrichment programs and youth sports. The aim of this study was to describe snacks, beverages, and physical activity (PA) practices in volunteer-led OST programs across five organizations in three states.An online survey including the Out-of-School-Time Snacks, Beverages, and Physical Activity Questionnaire was distributed to 1,695 adult leaders of enrichment and youth sports programs serving 5–12 year-old children in Maine, Massachusetts, and New Hampshire, USA. The response rate was 57.8%, with 980 leaders participating and 698  remaining after data cleaning procedures. Frequencies were calculated to describe snack, beverage, and PA offerings during typical meetings and whether healthy snack, beverage, and PA criteria were met. Criteria were developed a priori with the intent to capture co-occurring practices that together indicate healthy snack ; beverage (water over sugar-sweetened beverages); and PA environments .About half of enrichment leaders reported that snacks and beverages were provided during typical meetings vs. one-fifth of sports leaders. In 28.4% of enrichment programs, PA was offered at every meeting vs. 98.5% of sports programs. Among enrichment programs, 50.4 and 25.8% met healthy snack and beverage criteria, respectively, and 29.4% met PA criteria, with 27.6% meeting criteria in two or more areas, and 5.0% in all three. Among sports programs, 72.8 and 78.7% met healthy snack and beverage criteria, respectively, and 71.3% met PA criteria. Eighty-two percent met criteria in two or more areas, and 46.3% met criteria in all three.Most programs did not meet criteria for healthier snacks and beverages and opportunities for PA during typical meetings, indicating room for improvement in encouraging widespread adoption of these practices. Efforts to improve the healthfulness of snacks and beverages and increase opportunities for PA during volunteer-led OST programs are warranted.The online version of this article (doi:10.1186/s12889-017-4040-2) contains supplementary material, which is available to authorized users. Out-of-school-time (OST) programs offer an opportunity to promote healthy eating and physical activity (PA) to children. OST settings include structured, staff-led after-school programs, as well as volunteer-led enrichment and youth sports programs that take place before and after school, during school vacations, and on weekends –6. VolunOverall, studies of nutrition and PA practices in OST programs have highlighted room for improvement, with many programs offering energy-dense, nutrient-poor snacks, and a small percentage of program time utilized for PA , 11–15. Drink Right: Choose water over sugar-sweetened beverages; Move More: Boost movement and physical activity in all programs; and Snack Smart: Fuel up on fruits and vegetables [In 2011 the National AfterSchool Association adopted voluntary, evidence-based, Healthy Eating and Physical Activity (HEPA) Standards for OST settings . These cgetables .The goal of the current study was to assess the extent to which these healthy practices of offering water as the primary beverage, fruits and vegetables as snacks, and frequent opportunities for PA were being met during both enrichment  and youth sports  programs before the implementation of any HKOS interventions promoting them. Understanding current practices in these large volunteer-led OST programs can elucidate opportunities to improve nutrition and PA practices for millions of children and provide data against which future intervention efforts can be evaluated.An online survey was distributed to 1,695 OST leaders of enrichment or youth sports programs in Maine, Massachusetts, and New Hampshire, USA. Study staff collaborated with regional OST administrators to identify leaders, obtain contact information, and enlist support in survey distribution prior to the implementation of any HKOS interventions. Program leaders affiliated with one of five OST organizations  within the indicated states who were ≥18 years old and who worked directly with at least some children between the ages of 5 – 12 were eligible to complete the survey. Nine hundred and eighty leaders participated (57.8% of survey recipients), with 698 remaining in the sample after data cleaning procedures described below . Leaders were 94% non-Hispanic White in enrichment programs and 88% non-Hispanic White in sports programs, with a mean age of 48.0 years (SD = 9.5) and 42.1 years (SD = 6.3), respectively. Enrichment programs had more boys than girls participating as one of the two enrichment programs (Boy Scouts) included only boys. Sports programs consisted of both boys and girls . The survey was disseminated on a rolling basis to assess typical snack, beverage, and PA offerings. For enrichment programs , a link to the online survey was distributed via email to leaders prior to an HKOS training beginning in August 2013 for Boy Scouts and March 2014 for 4-H. For youth sports , recruitment took place via a prompt prior to taking an online training for coaches immediately prior to their sport’s season: August – November 2014 for Youth Soccer and Pop Warner, and October 2014 – January 2015 for YMCA youth sports. Because distribution of the survey was linked to the enrichment program year (academic year) and youth sports season (2–4 month seasons), enrichment programs had a longer period of data collection compared to youth sports , as well as additional questions about program-level demographics, beverages brought to typical program meetings by individual children, and snacks/beverages available outside of typical program meetings. The OST-SBPA measures nutrition and PA offerings as reported by the program leader, focusing on program-provided snacks, beverages, and PA opportunities during typical OST program meetings . TypicalLeaders’ survey data were exported from Qualtrics to SAS . Program-specific identifiers  were concatenated to form ID variables at the program level. A phased de-duplication procedure was enacted in order to identify and remove duplicate observations at the program-level, so that no OST programs would be over-represented in the data . This process began with an automated phase, using a SAS program to identify duplicates, followed by a manual check. In cases of clear duplicates, the observation that was recorded first was retained unless that observation was missing data on snacks, beverages, and PA, in which case this rule was overridden, and the next observation was retained. There were some cases of unclear duplicates (less than 1% of cases per OST organization); given the uncertainty as to whether these were true duplicate observations and the fact that they represented a small minority of observations, these cases were retained. After de-duplication, remaining data cleaning steps included examining distributions and outliers and recoding implausible values . The final cleaned dataset was restricted to include only programs with at least one child in the age range of interest (5-12 years), given that this was an intended inclusion criterion, and was also restricted such that cases in which leaders did not respond to at least one survey item about snacks, beverages, and/or PA were excluded.Frequencies were calculated by organization type (enrichment vs. youth sports), with variables of interest including program-provided snack, beverage, and PA variables from the OST-SBPA , as wellNo snacks at meetings, orIf the program provided snacks: (1) Fresh or processed fruits/vegetables were served at most or all meetings, and salty and sweet snacks were served at only some or no meetings, or (2) Fresh or processed fruits/vegetables were served at some meetings and salty and sweet snacks were served at no meetings.Snack success was defined as follows:If the program provided beverages: Water was provided at most or all meetings, and sugar-sweetened beverages were provided at no meetings.If individual children brought beverages: Water was brought to most or all meetings and sugar-sweetened beverages were brought to only some or no meetings.Beverage success was defined as follows:Enrichment programs offered opportunities for PA at most or all meetings, and when PA was offered, it was for >15 minutes per meeting.Sports programs offered opportunities for PA at every meeting, and when PA was offered, it was for >45 minutes per meeting.PA success was defined as follows:Additionally, composite variables were created to provide a more comprehensive indication of healthy snack, beverage, and PA practices. These success indicators were developed a priori by the research team with the intent to capture co-occurring practices that together indicate healthy snack, beverage, and PA environments as defined by the evidence-based HKOS principles  , 21.3% reported that individual children brought snacks, and 61.0% reported that snacks were not eaten during typical meetings. Given that most sports programs indicated that snacks were not provided for the group during typical meetings and the subsequent skipping of survey items about specific snack categories, there was a substantially smaller sample for these items . Given that most sports programs indicated that beverages were not provided for the group during typical meetings and the subsequent skipping of survey items about specific beverage categories, there was a substantially smaller sample for these items , 27.6% of enrichment programs met criteria in at least two of these three areas, and only 5% met all three. Among sports programs, 82.3% met criteria in at least two of these areas, and 46.3% met criteria in all three. The percentage of programs meeting each specific criterion is shown in Fig. This study demonstrates that volunteer-led OST programs are important settings for child health promotion. Findings showed that less than half of sports programs and only 5% of enrichment programs met criteria for healthy snack, beverage, and PA offerings during their typical program meetings. Similar results have been documented in structured, staff-led after-school programs, with many programs failing to provide fruits, vegetables, and water on a regular basis and demonstrating challenges meeting PA guidelines , 27. StuSome differences between enrichment and sports programs were observed in this study. Overall, each of the three healthy habits of interest  was reported by less than half of enrichment leaders, with only 5% of leaders reporting that all three of these were in place during typical meeting times. More than 70% of sports leaders reported success with each of these three habits, demonstrating a higher prevalence of each individually, although less than half of leaders reported success with all three.Among enrichment programs, the current findings indicate that a variety of snacks are commonly provided by programs during typical meetings, including both salty/sweet and fruit and vegetable snacks. While water was regularly provided by the majority of enrichment programs, sugar-sweetened beverages and juice were common with over one-half of leaders reporting on program-provided beverages indicating that sugar-sweetened beverages are served at least some of the time. A reduction in nutrient-poor, higher-calorie snacks and beverages provided in these settings could significantly impact children’s energy balance given that enrichment programs tend to meet over the course of a full academic year, with many children participating over multiple program years. Healthy habits learned through repetition in these settings may also extend to other settings , 31. TheSimilarly, findings pertaining to PA suggest that incorporation of PA is feasible within enrichment program meetings and indicate opportunities to promote more widespread adoption of this practice through activities like games and “active breaks”. While some enrichment leaders reported that PA is not a part of typical meetings, the majority reported that PA is offered regularly, with the most commonly-reported amount of PA time offered during typical meetings being 1–15 min. These findings highlight the opportunity for more enrichment programs to include PA and for most to increase total minutes of PA.Health promotion efforts during enrichment programs may influence children’s long-term health behaviors due to the lasting impact of the values instilled during these types of programs. For instance, it has been found that both adult Girl Scout and Boy Scout alumni display positive life outcomes historically cultivated by these programs, including a commitment to community service and civic engagement , 33. If As defined in this study, “typical meetings” capture the majority of enrichment program gatherings while sports programs’ “typical meetings” were defined as practices, which are one of two types of regular sports program gatherings, the other being games. Our results showed that many sports programs do not typically serve a snack during practices, and that water provided by individual children was the most commonly-offered beverage during these meetings. Physical activity in sports programs was high with nearly every team reporting PA at every meeting, and the majority offering 46 min or more. While these findings fit with pre-defined “success” criteria used in this study, results also suggest that it is important to target and monitor the food environment at games and other special events, where snacks and beverages are more likely to be available to youth sports participants. Sixty-eight percent of sports leaders reported that at least one type of snack was served at special events, and while fruits and vegetables were the most common offering, substantial percentages of leaders reported that salty and sweet snacks were available. Similarly, water was the most common beverage at special events, but substantial percentages of sports program leaders reported the availability of juice and sugar-sweetened beverages. Games take place more frequently  compared to enrichment programs’ special events, providing further rationale for incorporating them into youth-sports-focused health promotion efforts. Emerging research suggests that healthier options sold in concession stands during youth sports resulted in reduced sugar-sweetened beverage intake  and may Limitations of the current study include the possibility of social desirability biasing survey responses, as leaders may have over-reported practices that they perceived as desirable, such as healthier snacks and regular PA opportunities. The OST-SBPA instrument was validated against direct observation, attenuating this concern . AdditioKey strengths of this study include the use of validated survey items to assess snack, beverage, and PA practices impacting a large number of children attending volunteer-led OST programs from five national organizations. The ~700 OST leaders surveyed represent ~10,000 children participating in their programs (see Table The current results provide necessary descriptive information about food and PA environments in volunteer-led OST settings, contributing to the overarching knowledge base about OST, and also highlight implications of the unique attributes of different OST settings. Specifically, findings suggest that intervention efforts within enrichment programs may be most successful if targeting leaders who are providing snacks and beverages and planning PA curricula for typical meetings. Intervention efforts targeting sports programs should consider messages at the child and parent level given the prevalence of individually-provided beverages and should consider widening their focus to games. In sum, these results provide insights into the nutrition and PA environments of volunteer-led OST programs that serve millions of children and highlight considerations for future research, including the implementation and evaluation of health promotion efforts within these programs.The current study highlights room for improvement among both enrichment and sports programs, indicating that interventions aimed at improving the healthfulness of snacks and beverages, as well as increasing opportunities for and duration of PA during volunteer-led OST programs, are warranted. Findings also revealed variability in snack, beverage, and PA offerings between different OST organization types, which can inform the targeting of such intervention efforts. Evidence that some programs are already serving healthy snacks and beverages and offering ample opportunities for PA is promising for intervention efforts attempting to make these behaviors more widespread and normative across OST programs. Given that OST programs have the potential to reach millions of children nationwide, an understanding of current food, beverage, and PA practices across OST program types is a critical step toward increasing the effectiveness of OST programs as venues to reinforce healthy habits and help prevent childhood obesity. Leveraging OST programs’ reach and influence to consistently address physical health can transform these environments into settings promoting whole-child health and well-being, building upon OST organizations’ traditional focus areas, such as the promotion of leadership skills, teamwork, and civic engagement.


Want to get more experience in research, but find it difficult as an undergraduate? A summer research project may be the answer and there are many ways to organize this. Various universities around the world offer summer undergraduate research programs. These tend to be very competitive; hundreds, even thousands of students can apply for only a handful of positions. However, with some proactivity and strong planning, diligent undergraduate students can get accepted onto these prestigious programs. In this article, we outline the steps involved in selecting and successfully applying to a summer undergraduate research program. Various universities around the world offer summer undergraduate research programs (SURPs). These tend to be very competitive; hundreds, even thousands of students often apply for only a handful of positions. However, with some proactivity and strong planning, diligent undergraduate students can get accepted onto these prestigious programs.Various institutions around the globe offer SURPs. These tend to be fully funded studentships exclusively for undergraduate students, featuring 8–12 weeks at a laboratory/clinical institute undertaking research under the supervision of one of the local research teams. Admission to these programs is extremely competitive and it is sensible to apply to many in 1 year to improve chances of success. If successful, these programs can skyrocket your experience in the research environment and are a fantastic boost for your curriculum vitae (CV).SURP information is available throughout the Internet. Some webpages offer lists of SURPs such as that kindly produced by University of Cambridge’s Faculty of BiologyYou should apply to the SURPs that are the most relevant to you. Each SURP tends to offer a number of different research projects that you can either select from or are assigned to. Most of these tend to be laboratory-focused, with a series of lectures, seminars, and tutorials to enhance your experience and maximize your output from the program.Check the admissions criteria. Some SURPs only accept students from particular regions or countries, and some SURPs will only accept you if your latest end of year result is above a certain percentage. Some SURPs are designed for students with minimal previous research experience, while some are open to students from various research backgrounds. Typically, the SURP is applied for and carried out in the second year of an undergraduate science program, but these are variable.Check the deadline.It is helpful to apply for a SURP that is relevant to your future career prospects—it is great to be carrying out a SURP on the mechanisms of photosynthesis in plants but less so if you are aspiring to a career in academic neurosurgery. Particularly SURPs focus on specialized aspects, such as the Harvard Stem Cell Institute (HSCI) SURP, whereas some are more broadly focused on Biology, such as the Vienna Biocentre Summer Studentship. Despite this, research experience always provides generic skills, so it is still worth accepting a project in an area you will not later pursue.Check the structure of the program—some of these vary greatly. Some programs allow you to undertake the scheme at a date convenient for both you and the supervisor, whereas some are a fixed number of weeks.Some programs will require you to contact supervisors in advance It is advisable to contact supervisors at least 2 months in advance of the deadline for the SURP application.Bear in mind that many of the SURP applications will require referees. The requirements of referees vary from program to program. Some applications require a letter to be submitted directly to the program, some require a form to be filled out, and others will contact the referees after the deadline to directly obtain information about you. This should be taken into consideration when planning to complete your application before the deadline.Application requirements vary depending on the SURP. Typically the application will consist of the following items:A cover letter or personal statement, stating why you are applying for the program, why you are suitable, and what you wish to obtain from the program. Some programs require several cover letters with a fixed word limit.Your CV.Your university academic transcript. This will be obtainable from your relevant university portal, and should include all your grades and examination scores to date.Material from referees (see above).Yes. It is highly recommended that you do, considering the extremely competitive nature of the SURPs. If you are lucky enough to get admission more than one, you must quickly make a decision and contact your second preference to inform them you have opted for another program. This will enable time for the admissions tutors to select the next candidate on their list.Do not be disheartened if you get rejected from the SURPs of your choice. Most programs are extremely difficult to secure admission and any of the programs will be an excellent experience and adequate preparation for any research projects you are conducting in the coming years. If you are accepted, a welcome letter and an itinerary usually follow shortly after admission. Some of the programs have leisure and social activities included.SURP programs are run at various institutions across the globe and are extremely competitive.There are various admission criteria and requirements that differ from program to program that must be considered before application.Successful admission requires a strong application, diligence, and patience.


Research assistants (RAs) are hired at academic centers to staff the research and quality improvement projects that advance evidence-based medical practice. Considered a transient population, these young professionals may view their positions as stepping-stones along their path to graduate programs in medicine or public health.To address the needs of these future health professionals, a novel program—Program for Research Assistant Development and Achievement (PRADA)—was developed to facilitate the development of desirable professional skill sets  through participation in peer-driven service and advocacy initiatives directed toward the hospital and surrounding communities. The authors hope that by reporting on the low-cost benefits of the program that other institutions might consider the utility of implementing such a program and recognize the importance of acknowledging the professional needs of the next generation of health care professionals.In 2011, an anonymous, Web-based satisfaction survey was distributed to the program membership through a pre-established email distribution list. The survey was used to evaluate demographics, level of participation and satisfaction with the various programming, career trajectory, and whether the program's goals were being met.Upon the completion of the survey cycle, a 69.8% (125/179) response rate was achieved with the majority of respondents  reporting their 3-year goal to be in medical school  or nonmedical graduate school . Additionally, most respondents agreed or strongly agreed that PRADA had made them feel more a part of a research community , enhanced their job satisfaction , and provided career guidance . Overall, 85.6% of respondents (101/118) agreed or strongly agreed with recommending PRADA to other research assistants.High response rate and favorable outlook among respondents indicate that the program had been well received by the program's target population. The high percentage of respondents seeking short-term entry into graduate programs in health care-related fields supports the claim that many RAs may see their positions as stepping-stones and therefore could benefit from a professional development program such as the one described herein. Strong institutional support and sustainable growth and participation are other indications of early success. Further evaluation is necessary to assess the full impact of the program, particularly in areas such as job satisfaction, recruitment, retention, productivity, and career trajectory, but also in reproducibility in other institutions. This shift has resulted in the increased hiring of an employee pool that includes research assistants (RAs), study coordinators, quality improvement assistants, and other similar positions  at academic hospitals [In 21ospitals . A revieospitals ,7. This ospitals , and mayDespite not being hired as trainees , RAs may represent the next generation of medical and health care professionals . The jobThe understanding that a large percentage of RAs at one particular academic hospital fit this demographic  led to the development of such a program. This article details the impact that such a program can have on RAs' professional development as well as on the institutions they work for. By presenting the unique concept and the low-cost benefits of the program, the authors aim to encourage other hospitals to consider establishing similar programs.In 2010, a team of RAs at a large pediatric teaching hospital, mentored by a faculty physician, established the Program for Research Assistant Development and Achievement (PRADA) for the purpose of creating a structured learning environment similar to the institution-wide programs already in place for trainees, postdoctoral and clinical fellows, and faculty. The steps taken to implement the program included the following: (1) developing a clear mission statement and identifying goals, (2) receiving institutional endorsement, (3) creating a product of value to recruit RAs, (4) empowering RAs to run and expand the program, and (5) forming a means to evaluate the program's efficacy and impact.Once the mission statement and goals were outlined see , the proMission statementTo provide a structured and supportive learning community for research assistants, study coordinators, and other young professionals to develop into tomorrow's leaders in health careGoalsEnhance job satisfactionCreate an inclusive environmentEase acclimation into an academic clinical environmentProvide career insights through panel-style seminarsFacilitate skills development through lectures, workshops, and formal presentationFoster a service-oriented mind-set and promote community engagement through service and advocacy endeavors directed toward the hospital and surrounding communitiesThe initial anchoring product and recruiting tool of PRADA was a monthly seminar series at which invited guest speakers would speak on topics of interest to RAs, including the following: (1) professional guidance and skills , (2) health care-related career talks given by panels of health care professionals , and (3) relevant contemporary issues .Steadily increasing interest and participation prompted the creation of a unique email distribution list for PRADA. While used primarily as a way to broadcast programming, the email list would also serve as a tool for monitoring growth. Today, the list includes over 500 currently employed RAs at Boston Children's Hospital (BCH), over 50 RAs at neighboring institutions, and over 70 alumni  at medical schools and other health care professional training programs who expressed interest in continued involvement prior to leaving. Feedback, both solicited and unsolicited, from outgoing RAs indicated that many wished they had learned about the program earlier in their employment. This led to a partnership with the hospital's Department of Human Resources (HR), which now advertises the program throughout their hiring processes, not only to promote early engagement in PRADA, but also as a method to enhance recruitment.One of the earliest goals of the program was to have it run entirely by RAs. This was accomplished in 2012 when an executive board, overseen by two codirectors and their faculty advisor, was formed with representation from each of the following subcommittees: (1) Seminar Series and RA Grand Rounds, (2) Schoolwork Assistance , (3) Social Volunteerism , (4) Pre-Med Track , (5) Public Health, Community, and Advocacy , (6) Membership and Communications, (7) Alumni Affairs , (8) Science Writing Mentor Program , and (9) Interactive Music Program .Despite the transient nature of RA employment, the structure of PRADA has remained stable and has seen continued growth and participation. To ensure a seamless transfer of responsibility across committee positions, new executive committee members are recruited from within subcommittees and new subcommittee members are recruited at events year-round. Low operational costs also contribute to PRADA’s sustainability. Today, the only expenses that PRADA incurs are from the lunches served at noon seminars and the cost of running an annual summer conference for youth interested in health care-related careers.other were given the option to elaborate in a space below, accessible through branching logic. To determine if PRADA was meeting its goals, a list of specific questions were asked with the stated goals of PRADA in mind  electronic data capture tools hosted at BCH [In 2011, an anonymous quality improvement survey was administered to examine the demographics of PRADA’s target audience, level of participation in and satisfaction with the programming (data not provided), career trajectory of members, and whether PRADA was meeting its goals. Respondents were invited through the PRADA email distribution list, which contained 179 unique institutional email addresses at the time of the survey. Regarding career trajectory, participants were asked to answer the multiple-choice question, "In three years I would like to see myself in: same position, continued research with increased responsibility, graduate school, medical school, or other." Subjects who selected mind see . Subjectd at BCH .other and no respondents selected an option to remain in the same position.A total of 69.8% (125/179) of invitees responded, with 100% (125/125) of them submitting completed surveys. A total of 5 out of 125 (4.0%) were excluded based on previously established exclusion criteria pertaining to employment status at BCH, leaving a final sample of 120. The majority of respondents were non-Hispanic white , were female , were 22-26 years old , had a bachelor’s degree-level education , and were hired within the 2 years of survey administration . Most respondents  were seeking higher education, reporting their 3-year goal to be in medical school  or nonmedical graduate school . Only 8.4% (10/119) aimed to be in a research position with increased responsibility, 5.9% (7/119) were unsure, and 4.2% (5/119) aimed for a change in job with no research involvement. An additional 2.5% (3/119) selected Respondents agreed or strongly agreed that PRADA had made them feel more a part of a research community , enhanced their job satisfaction , provided career guidance , and connected them with research assistants in other fields . Additionally, 35.6% (42/118) agreed or strongly agreed that PRADA made them a better research assistant. Overall, 85.6% of respondents (101/118) agreed or strongly agreed with recommending PRADA to other research assistants. See agree or strongly agree on the Likert scale for this item. There was some indication that PRADA is on its way to meeting its second and third goals—to create an inclusive environment and to ease acclimation into an academic medical setting—given that 75.2% (88/117) of respondents indicated that they felt more a part of a research community and 47.9% (56/117) indicated that PRADA helped them meet RAs in other fields. However, further investigation is necessary to determine whether or not this has changed over time. Determining whether the final three goals—to offer career guidance, to facilitate skills development, and to promote a service-oriented mind-set through community engagement and advocacy opportunities—are being met requires further investigation, but high ratings of related programming (data not included) indicates that PRADA is on the right track toward meeting them. In all, outcomes indicate moderate success for PRADA bearing in mind the survey was conducted in 2011, 1 year prior to the expansion of the program into what it is today.The PRADA survey team set out to collect data for the purpose of quality improvement, as well as to assess career trajectory, and determine whether it was meeting its goals. The high percentage of RAs  indicating a 3-year goal of being in graduate or medical school supports the original hypothesis that many RAs see their positions as temporary posts along their way to higher education and more advanced positions. The premise that these RAs may find such a program valuable was supported by the large percentage of RAs who participated  and the large percentage of those who agreed or strongly agreed with recommending PRADA to others . Additional outcomes demonstrated that PRADA was meeting its first goal—to improve job satisfaction—with 55.9% (66/118) selecting Other observable indicators of success include a recent attempt to replicate the PRADA model at a neighboring Harvard-affiliated academic hospital by an alumnus, endorsement from the Boston Children’s Hospital Department of Human Resources, and inclusion of PRADA program materials in recruiting and hiring processes, which speaks to the value the institution sees in the program. In April 2015, the executive committee and the founding faculty physician received the 2015 Harold Amos Faculty Diversity Award, established to recognize and celebrate faculty who have made significant achievements in moving Harvard Medical School and Harvard School of Dental Medicine toward being a diverse and inclusive community.Limitations include a small sample size taken primarily from one institution. Additionally, the survey, having been designed for quality improvement purposes, did not have a control group, nor did the survey team obtain a baseline satisfaction for comparison. Additionally, the survey could not compare its demographic distributions against the hospital's records to demonstrate inclusivity. However, recent collaborations with HR have made this possible going forward.In response to the limitations of the survey administered in 2011, PRADA's survey team created a more substantial, Institutional Review Board-exempt, longitudinal study of its membership to further evaluate whether its programming has a significant impact on job recruitment and retention, job satisfaction, commitment to the institution and/or the field of pediatrics, as well as career trajectory. Additional questioning is being employed to better assess PRADA's progress toward meeting its goals, and demographic data will be compared with HR records to ensure inclusivity. The team also plans to explore reproducibility at other academic institutions.This program model offers RAs many unique and diverse opportunities to contribute to initiatives that they are passionate about without interfering with their work responsibilities. Organizing and/or participating in such activities facilitates the acquisition of skill sets considered desirable by admissions committees and expected of trainees -12. ThesPRADA is a low-cost, sustainable program that may improve overall job satisfaction by addressing areas of potential dissatisfaction for RAs. It also offers opportunities that promote growth, accomplishment, contribution, and corporate citizenship . Prelimi


The implementation of comprehensive alcohol management strategies can reduce excessive alcohol use and reduce the risk of alcohol-related harm at sporting venues. Supporting sports venues to implement alcohol management strategies via the Web may represent an effective and efficient means of reducing harm caused by alcohol in this setting. However, the feasibility and acceptability of such an approach is unknown.This study aimed to identify (1) the current access to and use of the Web and electronic devices by sports clubs; (2) the perceived usefulness, ease of use, and intention to use a Web-based program to support implementation of alcohol management policies in sports clubs; (3) the factors associated with intention to use such a Web-based support program; and (4) the specific features of such a program that sports clubs would find useful.A cross-sectional survey was conducted with club administrators of community football clubs in the state of New South Wales, Australia. Perceived usefulness, ease of use and intention to use a hypothetical Web-based alcohol management support program was assessed using the validated Technology Acceptance Model (TAM) instrument. Associations between intention to use a Web-based program and club characteristics as well as perceived ease of use and usefulness was tested using Fisher’s exact test and represented using relative risk (RR) for high intention to use the program.P=.02, RR 1.4, CI 1.0-2.9), perceived usefulness  and club size . The most useful features of such a program included the perceived ability to complete program requirements within users’ own time, complete program accreditation assessment and monitoring online, develop tailored action plans, and receive email reminders and prompts to complete action.Of the 73 football clubs that were approached to participate in the study, 63 consented to participate and 46 were eligible and completed the survey. All participants reported having access to the Web and 98% reported current use of electronic devices . Mean scores (out of a possible 7) for the TAM constructs were high for intention to use , perceived ease of use , and perceived usefulness . Intention to use the Web-based alcohol management program was significantly associated with perceived ease of use (A Web-based alcohol management approach to support sports clubs in the implementation of recommended alcohol management policies appears both feasible and acceptable. Future research should aim to determine if such intended use leads to actual use and club implementation of alcohol management policies. Worldwide, approximately 3.3 million deaths and over 200 diseases and injuries are attributable to excessive alcohol consumption . High leIn many nations, nonelite community sports clubs provide opportunities for organized sports participation for children and adults. A number of characteristics of such community sports clubs make them an attractive setting to address risky alcohol use and alcohol-related harm among players and supporters. First, sports clubs provide access to large numbers of players, spectators, and officials . For insStudies have demonstrated that implementing comprehensive alcohol management policies  in licensed venues can reduce harmful alcohol use in such premises ,18. SimiThe ability to modify the policies of service delivery organizations is suggested to be enhanced by the use of a variety of evidence-based implementation change strategies such as audit and feedback, consensus processes, training and resource provision . In an RWeb-based programs can be delivered at relatively low cost to large numbers of sports clubs and may represent a potential means of overcoming the logistical challenges of scaling up evidence-based alcohol management policies in this setting. Internet coverage is almost universal in high income countries such as Australia , extendiDespite the potential of Web-based programs, the benefits of such programs are often encumbered by low user engagement and uptake ,34. GiveCurrent access to and use of the Web and electronic devices by community sports club administratorsAdministrator perceptions regarding the usefulness and ease of use of a hypothetical Web-based support program to support club implementation of alcohol management policies and their intention to use such a programFactors associated with intention to use a Web-based alcohol management support programSpecific features of such a program that sports club administrators would find usefulA cross-sectional survey of club administrator representatives from community football clubs was conducted in the state of NSW, Australia. Clubs were based in major city, regional, and rural communities.Participating clubs were community level, nonelite football clubs across the 4 major Australian football codes: Rugby League, Rugby Union, Soccer/Association football, and Australian Football League. Eligible clubs had players over the legal drinking age (18 years of age and over), were a nonelite community sports club , had over 40 members, and held a current liquor license enabling sale of alcohol at the sports club and were currently participating in an existing alcohol management program delivered on a face-to-face basis (Good Sports) . AdditioA senior club administrator  of eligible clubs was identified from club records and sent a study information letter and invited to participate in the study on behalf of the club.An expert advisory group with representation from community sports clubs (senior club administrators), health promotion practitioners, implementation and behavioral scientists, and experts in organizational change informed the development of a computer-assisted telephone interview (CATI) survey, based on previously implemented surveys in sports clubs and other community settings ,39. The Club administrators were asked to report the club’s home ground postcode, football code , the number of senior (18 years of age and over) and junior (under 18 years of age) teams registered with the club, their current role within the club, the time (in years) they had been in that role, their age, and their gender.Club administrators were asked to report whether they had access to the Internet and whether they used electronic devices  to complete specific club-related tasks (at any location), including membership and player registration, game scheduling, managing club finances/book keeping, communicating with members, committee administration tasks, administration fundraising, and other events.The TAM is a validated instrument for prospectively assessing end-user intention to use Web-based programs ,37. TAM A total of 11 items from TAM were adapted for relevance to the sports club setting. A hypothetical Web-based program was described to club administrators via the CATI to determine clubs’ perceived usefulness, ease of use, and intention to use the program to support club implementation of recommended alcohol-management policies. The program was described to club administrators as able to monitor their progress of alcohol policy implementation, provide tailored feedback on their level of implementation, send prompts and reminders for required tasks, and provide unrestricted access to information and resources. Similar adaptation of the TAM has been employed in other community settings . Club adA total of 10 questions were used to assess the perceived usefulness of specific Web-based program features to support club implementation of an alcohol management program. Responses were recorded on a 7-point scale (1=strongly disagree and 7=strongly agree). Assessed program features were ability to complete program requirements in users’ own time, ability to complete program accreditation assessment and monitoring online, development of tailored action plans, email reminders and prompts to complete action items, access to support tools and resources, access to training and educational videos or interactive activities, program support via email or live chat, ability to communicate with club members (email), ability to communicate with other sports clubs in the program, and program-related peer comparison.Statistical analyses were conducted in SAS version 9.3 statistical software (SAS Institute Inc). Clubs were grouped by football code , and classified according to geographical location  using the Australian Standard Geographical Classification (ASGC) based on the Accessibility/Remoteness Index of Australia score (ARIA) and size . All statistical tests were 2-tailed with an alpha of 0.05.For aim 1, simple descriptive statistics were used to describe sports club administrators’ access to and use of the Web and electronic devices to undertake club tasks. For aim 2, similar to other TAM studies ,42, the For aim 3, again similar to other TAM studies ,42, the Ethics approval was obtained from The University of Newcastle, Human Research Ethics Committee (H-2008-0432).A total of 73 community sporting clubs were approached to participate in the study, of which 63 consented to participate (86%). Of these 63, 17 were ineligible and 46 completed the survey (73% of eligible). Of the participating clubs, the largest proportion were Rugby League clubs  and Rugby Union clubs , the majority of clubs  were located in major cities, and just over half the sample  was classified as large clubs. Most club administrator representatives held the role of club president  or secretary  and were male , with a mean age of 48 years and a mean number of 4.3 years in that position .Most (98%) football club administrators reported current use of electronic devices for club-related tasks and all reported having access to the Web when undertaking these tasks. The proportion of clubs that reported undertaking specific tasks using electronic devices is reported in P=.02) and perceived usefulness of the program (P=.03). Club size was found to be positively significantly associated with high intention to use such a program (P=.02).Overall, there was a high level of agreement regarding the usefulness of each of the proposed program features. All club administrators agreed or strongly agreed that the ability to complete program requirements within their own time would be a useful feature. Greater than 90% of club administrators agreed or strongly agreed that it would be useful for the program to enable completion of program accreditation assessment and monitoring online (96%), develop tailored action plans (96%), send email reminders and prompts to complete actions (96%), provide access to support tools and resources (96%), include program support (email or live chat) (94%), and provide program-related peer comparison (91%). A high level of support was evident for access to videos or interactive activities for training and education (83%), an ability to communicate with club members by email (78%), and an ability to communicate with other sports clubs in the program (70%).This is the first study to assess the feasibility and acceptability of a Web-based program to support the implementation of alcohol management policies by community sports clubs. There was universal access to the Web and use of electronic devices when undertaking club-related tasks among clubs. The vast majority (89%) of club administrators reported high behavioral intention to use a Web-based program to support their club’s implementation of recommended alcohol management policies. Furthermore, both perceived usefulness of a Web-based alcohol management program and its perceived ease of use were positively associated with intended use. The findings suggest that there is considerable potential for a Web-based program to support sports clubs in the implementation of recommended alcohol management policies and in doing so to make a contribution to reducing alcohol-related harm in this setting and the community at large.The study findings are comparable to similar studies conducted in other settings. For example, high intention to use Web-based programs to support implementation of health-related programs have been reported in childcare services , health In this study, larger clubs had a significantly higher level of intended program use (100%) compared to smaller clubs (76%). This may be due to greater complexity of managing alcohol use in larger clubs, requiring greater workforce, resources, and infrastructure to manage. Potentially, the use of Web-based programs to coordinate the implementation of alcohol management policies in these settings may be perceived as of greater benefit. Similarly, as in licensed venues, sports clubs experience a high number of alcohol-related incidents ,46, Web-The results of this study should be considered with respect to its strengths and limitations. The strengths of this study include the application of a validated tool  to assesFurther studies are required to determine if sports clubs will actually use such a program if it existed and to show whether such a program has the intended effect of supporting clubs to implement recommended alcohol management policies.


The Homeland War in Croatia was still far from conclusion when, one day, the phone rang in the office of one of us (SV-P). “I heard you could help me obtain a DNA sequencer,” the voice on the other side said. “We need it to identify the victims from mass graves in Bosnia.” Unfortunately, the help was no more than providing a few connections that later proved useful. At the time, we did not even suspect that twenty-some years later we would write these words.The voice was of Dragan Primorac, then a postdoctoral fellow at the University of Connecticut. His “I-do-not-take-no-as-the-answer” attitude took him along an unusual and unusually successful trajectory . In the This application has been quite successful as were his other endeavors. He published numerous peer-reviewed and highly cited papers in the most prestigious scientific journals. While teaching at universities of Split and Osijek in Croatia and Pennsylvania State University and the University of New Haven in the United States, Dr Primorac has been the driving force behind the founding, funding, and running The International Society for Applied Biological Sciences (ISABS). Founded initially with the main objective to produce the biennial series of cutting-edge conferences in the areas based on applied genetics, ISABS became a recognized force in the promotion of forensic science and its integration with anthropology and clinical medicine. Among the most recent recognitions of this role, earlier this year the Board of Directors of the American Academy of Forensic Sciences accepted unanimously ISABS as its associate member, the second such organization in its 70-year history .ISABS Conferences are Dr Primorac’s particular achievement. For twenty years, he has bravely pursued his vision of a biennial gathering of scientists of all generations and levels of achievement, from undergraduate students to Nobel Prize winners, to discuss the fields that apply similar or same methods of modern genetic analysis. Starting in 1997 as the European-American Intensive Course in PCR-based Clinical and Forensic Testing, the program nimbly adjusted at each subsequent conference to the developing technology and technological achievements . Even more significant has been the introduction into the program of related fields that use the same technology. By virtue of integration of anthropologic genetics/genomics and clinical genetics/genomics, the program became a rather unique cross-section of fields initially related mostly by technology, but today also by the scientific and practical interests. For example, derivation of phenotype from genotype is as much of major interest to forensic science as it is to anthropology and clinical practice.To maintain the program at the cutting-edge level and fresh, after the Eighth Conference program directors (Dr Primorac and the two of us) passed the baton to the new generation, Manfred Kayser (University of Rotterdam) and Tamás Ördög . Affiliation of ISABS with institutions such as Mayo Clinic, American Academy of Forensic Sciences, Pennsylvania State University, and others has never been stronger leading to the ever increasing depth and breadth of the program.Croatian Medical Journal that published special issues containing the total of more than 220 scientific papers presented at conferences  , presenters , and the seventy countries of their origin. Over the years, ISABS has collaborated with the As for the authors of this text, they could not be more grateful to Dragan for having involved them in this project from the very beginning, for sharing credit for its success while carrying all the burden of funding and organizing and, last but not least, for his dedicated friendship.


BCR-ABL1 mRNA levels in peripheral blood of chronic myeloid leukemia patients is a strong indicator of response to tyrosine-kinase inhibitors (TKI) treatment. However, additional prognostic markers are needed in order to better classify patients. The hypothesis of leukemic stem cells (LSCs) heterogeneity and persistence, suggests that their functional evaluation could be of clinical interest. In this work, we assessed the primitive and progenitor fractions in patients at diagnosis and during TKI treatment using functional in vitro assays, defining a “functional leukemic burden” (FLB). We observed that the FLB was reduced in vivo in both fractions upon treatment. However, different FLB levels were observed among patients according to their response to treatment, suggesting that quantification of the FLB could complement early molecular monitoring. Given that FLB assessment is limited by BCR-ABL1 mRNA expression levels, we developed a novel detection method of primitive cells at the DNA level, using patient-specific primers and direct nested PCR in colonies obtained from functional in vitro assays. We believe that this method could be useful in the context of discontinuation trials, given that it is unknown whether the persistent leukemic clone represents LSCs, able to resume the leukemia upon TKI removal.Quantification of  BCR-ABL1, which encodes a constitutively activated protein with tyrosine kinase activity [BCR-ABL1 transcripts in peripheral blood (PB) [BCR-ABL1 transcripts in PB.Chronic myeloid leukemia (CML) is a hematopoietic disorder in which myeloid cells proliferate excessively given to the abnormal activation of the chimaeric protein BCR-ABL1. The reciprocal translocation t9;22)q34;q11) gives rise to the fusion gene 2, and a ∼140kbp region in ABL1 (intron 1). Therefore, each patient harbors a specific genomic breakpoint, which requires personalized characterization in order to design patient-specific primers for PCR detection at the DNA level. Previous reports have shown that BCR-ABL1 can be detected at the DNA level in patients under sustained deep molecular response, even in those that attained a treatment-free remission (TFR) after TKI discontinuation [BCR-ABL1-positive cells constitute a primitive fraction, i.e. LSCs, with the potential capacity of causing disease, or whether they represent a population of cells unable to resume the leukemia.Breakpoints that lead to in vitro assays, in CML patients at diagnosis and during TKI treatment. In addition, we show that it is possible to detect residual primitive cells by in vitro functional assays at the DNA level, which enables independence from BCR-ABL1 expression levels. This method is of potential interest for assessing residual disease in future TKI discontinuation trials.In order to study the dynamics of primitive and progenitor fractions, we report the evaluation of such populations at the RNA level by functional in vitro assays that enable to retrospectively quantify cells in the primitive and lineage-restricted progenitor fraction, respectively. Aiming to evaluate whether the dynamics of these populations can vary among patients at diagnosis and under TKI treatment, we performed both assays with PB or bone marrow (BM) samples from CML patients  and short-term Colony Forming Units (CFU) assays are functional ts Table . In ordeBCR-ABL1 mRNA levels) and frequency (i.e. number of leukemic cells), we considered both factors as a single one, defined as primitive or progenitor “functional leukemic burden” (FLB). For each patient, the value of FLB was calculated as the median of %BCR-ABL1/ABL1 measured in each colony or pool of colonies  extraction and sequencing of the rearrangement breakpoint by long-range multiplex-PCR followed by next-generation sequencing (NGS) (BCR-ABL1 transcripts in PB under Imatinib treatment (400mg daily), attaining a MR3.0 at 18 months. A PB sample at 18 months of TKI treatment was used for CD34+ cells isolation, followed by a 6-weeks-LTC-IC assay . Quality of the starting material was evaluated by detecting an independent gene at the DNA level, and colonies from a 2-wks-CFU assay at 6 months of treatment were used as positive controls. Nested PCR showed improved sensitivity compared to single PCR (data not shown), and it was able to detect a low proportion of BCR-ABL1+ individual colonies in the primitive fraction (5 out of 20)  . The pat+ cell population of a viable fraction of stem-like leukemic cells. For this, we used the most rigorous in vitro LSC detection technique (6-weeks LTC-IC) to evaluate the effects of TKI therapies on the most primitive leukemic cell compartment. As stated above, we considered the FLB to reflect a population of primitive or progenitor cells able to self-renew, give rise to daughter cells during in vitro functional assays, and produce variable levels of BCR-ABL1 mRNA. We had to adopt this definition because the evaluation of pooled colonies did not allow us to distinguish the effects of variable frequency of BCR-ABL1-positive colonies, from the effects of variable levels of BCR-ABL1 expression among individual colonies. Despite this limitation, dynamics of the primitive fraction during TKI treatment measured by FLB was comparable to previous reports based on phenotypically defined LSCs [The assessment of individual LTC-IC-derived cells is particularly challenging: first, LSCs can be highly quiescent and, therefore, might not generate any detectable progeny in these assays . Second,ned LSCs , 15, comBCR-ABL1 overexpression in primitive cells (lin-CD34+CD38-) and mature (CD34+CD38+) progenitors may contribute to the failure of TKIs to prevent disease progression [BCR-ABL1 gene, subtype of stem cell in which BCR-ABL1 is expressed, differences in transcript expression patterns between patients, and differential interactions with the BM microenvironment and the immune system [in vitro assays.Previous reports suggested that gression . Howevere system –23. Heree system , 15, addBCR-ABL1-positive clones assessed at the DNA level [BCR-ABL1 mRNA in individual colonies from patients with undetectable deep molecular response have been reported, such levels were very low [-ABL1 DNA breakpoint with LTC-IC assay for separation of the primitive hematopoietic fraction, enables us to measure residual leukemic disease at the LSC level. Therefore, this method could be particularly useful in situations where the concurrently low burden of leukemic primitive cells and very low BCR-ABL1 mRNA expression levels, limit the sensitive detection of residual disease. With the purpose to validate this strategy, we will apply it in a currently recruiting TKI discontinuation trial in Argentina; we believe that in the future, this study may result of great interest in order to understand patients´ heterogeneous capacity of successfully maintaining TFR.The fact that longer treatment is associated with lower relapse rates upon TKI interruption suggests that the risk of relapse might be related to the achievement of certain depth of MR below the detection limit of conventional RT-qPCR . In multNA level , or at tNA level . HoweverNA level . For thivery low , suggestBCR-ABL1 mRNA levels in the primitive fraction during TKI treatment could be of clinical utility in order to improve and complement molecular monitoring in PB. Finally, we propose that the residual leukemic burden should be further assessed by gDNA PCR at the LSC level.Overall, our results suggest that assessment of 3 1 mM, NH4Cl 170mM, pH 7.3), and a low-speed centrifugation step (12-15 minutes at 200xg) for removal of the platelet-rich fraction. Up to 2x108 mononuclear cells were used for CD34+ cells isolation. Patients were classified according to their response to TKI treatment as follows: patients that were not able to achieve early response milestones and that would be considered as cases of warning or treatment failure according to the European Leukemia Net [BCR-ABL1 transcripts, or secondary malignancies, were considered as SR patients; patients that sustained the requirements to be considered as optimal responders up to 1 year of TKI treatment, and did not develop SR events were considered as NR patients.The project was approved by the Institutional Review Board, at Instituto Alexander Fleming, Buenos Aires, Argentina. After giving written informed consent, BM or PB samples were obtained from newly diagnosed, untreated CML patients in CP, or from patients at different time points during TKI treatment. Mononuclear cells were isolated by density-gradient centrifugation  for 30 minutes at 480xg, followed by one wash in PBS, a red cell lysis step . When available, 10,000 cells were used for purity assessment by flow cytometry.In order to enrich samples in the progenitor and primitive fraction, we performed a positive selection using CD34 MicroBeads (Miltenyi Biotech), according to the manufacturer’s instructions. The CD34+ cells were plated in duplicate in p35 culture dishes containing 1mL of enriched methylcellulose , and incubated at 37°C in a humid chamber. After 14-18 days, hematopoietic colonies were counted under the microscope, and individual or pooled colonies (made of 4 to 6 colonies) were plucked from methylcellulose and put into 500μl of RPMI medium . Up to 10 pools of colonies were evaluated per patient, depending on the yield of the assay. All types of colonies were used for RNA isolation , and no differences in BCR-ABL1 mRNA expression were found among different types (data not shown). After centrifugation, pellets were resuspended in 100μl of lysis solution , and kept at -20°C until RNA extraction was performed.500 CD34+ cells were plated in collagen-coated p35 culture dishes containing 2mL of Long-term culture medium , over a feeder layer composed of murine M2-10B4 and SI/SI cells producing hIL-3, hSCF and hGCSF (kindly provided by Stem Cell Technologies), previously irradiated at 80Gy. Transfected M2-10B4 and SI/SI cells were selected with G418 and Hygromicin B every 2 or 3 passages. One half of the medium was replaced every week. After 6 weeks, adherent and non-adherent cells were harvested, and 20,000 cells were used for short-term CFU assays, as described above.5,000 CD34260/A280 ≥ 1.7) were used for retrotranscription using Superscript II . qPCR was performed using primers and probes for BCR-ABL1 and ABL1 from the European against cancer program [BCR-ABL1/ABL1 ratios were obtained directly from their data.Total RNA was extracted from single or pooled colonies using RNAqueous-Microkit . RNA was eluted in 18μl of elution solution at 75°C; only samples with acceptable purity . Multiplex long-range PCR was performed using different sets of primers as previously described . The PCRhttp://broadinstitute.github.io/picard). The fusion points were localized using CREST  [ABL1 and BCR reference sequences in order to identify each segment.In order to find the chromosomal translocation point, reads were aligned using the Subjunc aligner included in the Subread package (v1.5.0-p3)  and huma v0.0.1) , which rSequence corresponding to patient-specific fusion breakpoint was used for PCR primer design (Primer3Plus). Short and long-term culture assays were performed as described above. Individual colonies were plucked from methylcellulose and subjected to direct nested PCR without a DNA extraction step. For this, cell lysis was performed by plucking individual colonies with a p20 tip set at 5μl, into 50 μL of the following mixture: GoTaqFlexi PCR buffer  supplemented with NP-40 0.5%, Tween-20 0.5%, and proteinase K 0.91 mg/mL. Lysates were incubated for 1 hour at 60°C, followed by 15 minutes at 95°C. 10% of the final volume was used for first-round PCR. This PCR product was diluted ten-fold for second-round PCR.U test). A mixed-effects model was used in ANOVA .Data was plotted using GraphPad Prism software or R project. Statistical analysis of the data was performed with Infostat Software . When the assumptions of normality and homoscedasticity of the data were not met, variance was modeled previous to performing a parametric test (ANOVA), or analyzed by non-parametric tests (Mann–Whitney