Journal clubs are an essential tool in promoting clinical evidence-based medical education to all medical and allied health professionals. Twitter represents a public, microblogging forum that can facilitate traditional journal club requirements, while also reaching a global audience, and participation for discussion with study authors and colleagues.The aim of the current study was to evaluate the current state of social media–facilitated journal clubs, specifically Twitter, as an example of continuing professional development.A systematic review of literature databases  was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of Twitter, the followers of identified journal clubs, and Symplur was also performed. Demographic and monthly tweet data were extracted from Twitter and Symplur. All manuscripts related to Twitter-based journal clubs were included. Statistical analyses were performed in MS Excel and STATA.R2=.98), and tweets per month (R2=.72). Cumulative tweets for specific journal clubs increased linearly, with @ADC_JC, @EBNursingBMJ, @igsjc, @iurojc, and @NephJC, and showing greatest rate of change, as well as total impressions per month since establishment. An average of two tweets per month was estimated for the majority of participants, while the “Top 10” tweeters for @iurojc showed a significantly lower contribution to overall tweets for each month (P<.005). A linearly increasing impression:tweet ratio was observed for the top five journal clubs.From a total of 469 citations, 11 manuscripts were included and referred to five Twitter-based journal clubs . A Twitter-based journal club search yielded 34 potential hashtags/accounts, of which 24 were included in the final analysis. The median duration of activity was 11.75  months, with 7 now inactive. The median number of followers and participants was 374 (IQR 574) and 157 (IQR 272), respectively. An overall increasing establishment of active Twitter-based journal clubs was observed, resulting in an exponential increase in total cumulative tweets (Twitter-based journal clubs are free, time-efficient, and publicly accessible means to facilitate international discussions regarding clinically important evidence-based research. Journal clubs are a well-established method to facilitate interactive peer review and critical thinking in clinical evidence-based medical education ,2. FurthAn unprecedented expansion in the medical use of social media, such as Twitter, Facebook, LinkedIn, and YouTube, has followed the uptake seen with the general public. Twitter is a public, microblogging forum where users  upload short messages comprising a maximum of 140 characters, with/or attached photos, documents, and links to other media such as videos, presentations, or journal articles. In most cases, these “tweets” are linked to a theme, often centralized using a “#”  for easy view and discovery by other users. Users are also able to “follow” the tweets of other users. Specific events  often promote an official hashtag to allow users to follow all discussion relating to the event . DedicatWhen combined with Twitter, journal clubs are able to function in a similar way to traditional journal clubs, with the advantage of a global audience and participation for discussion. Twitter-based journal clubs are able to be easily linked using a hashtag , allowing anyone to follow and contribute with a unique identifiable username. A central moderator is able to inform followers of the article to be discussed well ahead of time for perusal. Furthermore, authors of discussed articles are often invited as participants, enabling real-time interaction. Online journal clubs allow for international and increased participation, even when used with other less mainstream platforms ,11. AddiThe aim of the current study was to evaluate the current state of journal clubs facilitated by social media, specifically Twitter, as an example of continuing professional development and through a systematic review process.A systematic review was undertaken based on guidelines outlined by the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement .A systematic literature search was performed using literature databases  using synonyms relating to “social media” and “journal club” in November 2014 see  14,15]..15]. RefFollowing review of published reports, Twitter was by far the most popular and commonly used social media outlet for journal clubs. A systematic search of Twitter was performed to identify all relevant hashtags to be included in the current study, including using the search box and the terms “journal club” and “jc”, as well as reviewing the users who were following all identified journal clubs, initially using those identified in the literature search. Journal club selection was performed by 2 independent evaluators , and any discrepancies were resolved.Inclusion criteria for hashtag analysis included journal clubs related to health care. Hashtags were excluded from analysis if they were not Twitter-based journal clubs, English-speaking, if the hashtag was not used completely for the purpose of a journal club, or if the hashtag represented institutional or private journal clubs. A final search was performed on the Symplur website, which tracks social media related to health care.Basic Twitter-based data was extracted from the relevant journal club Twitter-based websites. If available, such information included speciality, location, journal club tweets, and Twitter followers. Journal club tweets refer to the number of posts generated by a single journal club account. Data extraction from Symplur was achieved by searching each relevant hashtag (#). Data extracted from Symplur included hashtag commencement date, hashtag inactivation date, total tweet count, tweet count per month, number of tweeters, and total impressions. “Hashtag activation date” was defined as first month with greater than 5 tweets with the relevant hashtag. “Hashtag inactivation date” was defined as the starting point of 3 consecutive months with <6 tweets per month. Tweet count refers to the total number of posts containing the relevant hashtag. Number of tweeters was defined as the number of unique individual Twitter accounts that generated a post containing the relevant hashtag. Impressions, or reach, refer to the number of Twitter users using a particular hashtag and the sum of their respective followers—thus a surrogate for the number of users exposed to a particular hashtag. Detailed statistics of the top five journal clubs , as determined by rate of increase in cumulative tweets, were retrieved for each month from Symplur.Data from published manuscripts were insufficient for compilation, so a descriptive analysis was performed. Twitter hashtag data were collated and analyzed using a Microsoft Excel 2003 database. Figures were created using STATA v.12.0 SE.The final search strategy resulted in retrieval of 469 citations, including 47 duplicates, 381 irrelevant citations, 18 conference abstracts, 9 citations unrelated to journal clubs, and 9 based on blogs or other resources . Eleven Three manuscripts referred to #ALiEMJC/@AnnalsofEM -18 , while the remainder have grown out of specialty interest groups and as yet appear to have no official alignment.Of the manuscripts reviewed, three journal clubs were officially affiliated with peer-reviewed journals  with a median number of active participants of 157 (IQR 272). Monthly activity was calculated with a median “tweets per month” of 203 (IQR 317) and median “impressions per month” of 165,538 . Following inception, and as of October 30, 2014, seven of the included journal clubs had become inactive .R2=.98) as well as tweets per month (R2=.72).Overall, after exclusion of inactive journal clubs, an increasing establishment of Twitter-based journal clubs  was obseR2>.95) increase in tweets was estimated as being greatest for @NephJC (722 tweets/month), @igsjc (613 tweets/month), @EBNursingBMJ (417 tweets/month), @iurojc (345 tweets/month), and @ADC_JC (255 tweets/month). These trends were also observed in the impressions/month rankings  stages was observed. Specifically, the linearly modeled . Of those appearing in the “Top 10” for each month during journal club discussions, the majority were classified in the “Top 10” for the first or second time.Tweets and impressions for each of the top five journal clubs as determined by tweets/impressions per month  were analyzed. Subgroups were created based on the “Top 10” participants for each month (as determined by Symplur) versus the remaining participants. An average of two tweets per month, was estimated for participants outside of the “Top 10” tweet contributors for each month . The conR2>.87 for all; In an attempt to measure “reach” for each journal club, while considering large tweet traffic from these accounts in moderating and advertising, an impression:tweet ratio was calculated for each journal club user account. This impression:tweet ratio was shown to be linearly increasing for all journal clubs (There were an estimated 200 million users per month actively tweeting an average of 500 million times per day in 2013, depicting Twitter as a contemporary, ever-changing social media environment. While recent reports in media outlets suggest that the rate of Twitter use overall may be declining, the findings of this systematic review of published literature and Twitter suggest that Twitter-based journal clubs are an expanding method of continuing professional development and a platform for global interaction. Published reports describe positive initial uptake and support from their respective medical communities ,16-18, wOverall, we have observed an increasing participation in Twitter by the medical and allied health community, evidenced by an increasing year-to-year establishment of new journal clubs  and expoSimilar increases in Twitter participation have been observed for medical conferences  and estaWhile this relationship between social media and traditional academic media continues to grow, the use of Twitter for continuing professional development is an attractive venture. However, the freedom of voluntary participation complicates the establishment of an accurate and efficient record of participation for appropriate ethical acknowledgement for continuing professional development requirements by credentialing authorities. To date, no objective evaluation assessing the knowledge uptake and retention resulting from microblogging journal club is available . Some stFOAM encapsulates a collection of resources and tools for learning in medicine that are transforming medical education . FOAM haWhen individual journal club performance was considered, we observed a clear increase in overall tweets and impressions for established journal clubs, with some increasing at a rate as high as 722 tweets/month. However, month-to-month tweeting was observed to be highly variable. This variability could relate to diversity in interest among followers regarding the topics discussed or reduced participation of influential or high-volume tweeters for various reasons. There may also be limitations in access to articles discussed, particularly for individuals without institutional or individual journal access for those articles that are not open access. Where possible, some journal clubs, such as #urojc, provide open access to the discussed articles in order to remove this limitation .In considering the determinants of journal club performance, subgroup analysis suggested that a large proportion of tweets each month were from those in the “Top 10”, with the remaining participants expected to contribute two tweets per journal club discussion . HoweverThis study is an analysis of social media at a point in time, when social media is known to be ever evolving. Much of the Twitter-based analytics relied on third-party services, such as Symplur, which was intended to focus on social media related to health care. Further, there are inherent limitations with the use of Twitter-based outcome measures, such as impressions, as a surrogate for reach. We were unable to measure the pattern of growth in followers or participants through data acquisition restrictions. There is also no current way to measure the passive value of journal clubs, specifically relating to users who are following the journal club discussion, and thus acquiring educational value, but not actively participating. We acknowledge that the number of included manuscripts is small, reflecting the current state of published literature relating to Twitter-based journal clubs. This review will serve as a check point and reference for the development of enhanced Twitter-based journal clubs by other medical craft groups internationally or loco-regionally.This systematic review provides an illustration of early trends in the development of journal clubs using Twitter as a communication medium. Twitter-based journal clubs provide access to free, time-efficient, and high-level discussions on clinically important issues and equal participation opportunity for users. Twitter provides an unprecedented method of networking and formation of friendships with colleagues, which can be harnessed to educate, initiate research collaborations, and even canvass opinions with difficult cases in the time between conferences. Hence, the role of social media in continuing professional development will continue to evolve with increasing engagement by journals, conferences, and FOAM sources. Furthermore, in the midst of busy clinical duties, microblogging using Twitter provides a unique pathway to access and engage in discussions with peers and professional leaders.


Much debate has arisen from research on muscle synergies with respect to both limb impedance control and energy consumption. Studies of limb impedance control in the context of reaching movements and postural tasks have produced divergent findings, and this study explores whether the use of synergies by the central nervous system (CNS) can resolve these findings and also provide insights on mechanisms of energy consumption. In this study, we phrase these debates at the conceptual level of interactions between neural degrees of freedom and tasks constraints. This allows us to examine the ability of experimentally-observed synergies—correlated muscle activations—to control both energy consumption and the stiffness component of limb endpoint impedance. In our nominal 6-muscle planar arm model, muscle synergies and the desired size, shape, and orientation of endpoint stiffness ellipses, are expressed as linear constraints that define the set of feasible muscle activation patterns. Quadratic programming allows us to predict whether and how energy consumption can be minimized throughout the workspace of the limb given those linear constraints. We show that the presence of synergies drastically decreases the ability of the CNS to vary the properties of the endpoint stiffness and can even preclude the ability to minimize energy. Furthermore, the capacity to minimize energy consumption—when available—can be greatly affected by arm posture. Our computational approach helps reconcile divergent findings and conclusions about task-specific regulation of endpoint stiffness and energy consumption in the context of synergies. But more generally, these results provide further evidence that the benefits and disadvantages of muscle synergies go hand-in-hand with the structure of feasible muscle activation patterns afforded by the mechanics of the limb and task constraints. These insights will help design experiments to elucidate the interplay between synergies and the mechanisms of learning, plasticity, versatility and pathology in neuromuscular systems. The manner in which the nervous system coordinates the multiple muscles in the body is complex. It has been studied for decades, but a more full understanding is needed to enable the development of effective evaluation and treatment methods in disorders that cause neuromuscular disability such as cerebral palsy and stroke. In addition, the computational control of robots has and will continue to improve as the brain’s methods of muscular control are progressively reverse-engineered. Here, we study the capacity of arm muscles to regulate the stiffness of the hand for tasks such as using tools, stabilizing hand-held objects, and using doors. Using a simplified but generalizable model, we show that there will be necessary trade-offs in the functional capabilities of the limb if the nervous system chooses to control muscles in functional groups. This adds to our understanding of the consequences of different strategies to control muscles for real-world tasks with multiple and often competing demands. It enables future research and clinical experiments on the learning and execution of the multiple tasks of varying difficulty encountered in real life. It also sheds light on the design of control strategies for robots to operate in human and unstructured environments. Limb impedance control by the central nervous system (CNS) has been a subject of much study and debate over the past three decades. Numerous experiments and theoretical analyses have studied the biomechanical and neuromuscular capabilities of the CNS to regulate the impedance of a limb e.g., –22). The. The22])The existence and interpretation of muscle synergies is controversial and has received much attention in the recent literature –29. SyneThere is extensive literature on the analysis and synthesis of endpoint stiffness in robotic limbs , 30–33. In this study, we investigate the effects of muscle synergies on endpoint stiffness synthesis and energy consumption . To thisfeasible activation set’ [Importantly, our work takes on the approach that we are interested in finding the families of feasible endpoint stiffness realizations throughout the workspace of the limb. That is, how much can the nervous system control the size, shape  and orientation of endpoint stiffness ellipses for all limb postures? Due to muscle redundancy, there may be multiple ways to achieve any one possible stiffness ellipse. That set of multiple neural commands that can achieve a given realization is its ‘ion set’ , 36. We As mentioned in the Discussion, this neuromechanical approach emphasizes the feasibility of neuromechanical actions and allows us to consider several potential confounds when comparing across studies. Such studies may include examination of the extent, efficacy and nature of training, the influence of limb postures on task goals specified by the experimenter, and the implicit neural strategies specified by the CNS with regard to stiffness regulation in health and disease. Our results also allow us to discuss how learning, experimental design, and neural strategies affect our ability to tune endpoint stiffness.Kend, is a matrix that is calculated as a function of individual musculotendon stiffnesses, which are the elements of the matrix Kmuscles. The individual musculotendon stiffness generated by each muscle is represented by a numerical variable that is, in effect, a lumped parameter model introduced by Hogan and Mussa-Ivaldi [We use a simplified planar arm model with 6 muscles similar to those that have been used in other theoretical and computational studies , 13, 37 a-Ivaldi , 13 that details , 13, 37,Kend) to an ellipse that represents the characteristics of this matrix—shape —measured by the matrix condition number, and orientation of the major axis with respect to the x-axis.We use workspace constraints identical to those used in  to produKend, as a function of muscle active stiffnesses, Kmuscles. As a point of clarification, we focus on muscle active stiffness that results from the feedforward activation of the muscle such as during force production or co-contraction. We do not include passive stiffness, which normally refers to the inherent material properties of the limb or muscles with no muscle activation. This could arise, for example, from tendon properties. Similarly, as mentioned in the Discussion, we do not include the time-delayed stiffness resulting from reflexes, often called reflexive stiffness. In our formulation, Kend relates the vector of differential endpoint displacements to differential endpoint forces:Kjoint, relates the vector of differential joint angle displacements to differential joint torques:J . As we will see in the results, this one-dimensional manifold in muscle activation space does not allow the realization of the arbitrary endpoint stiffness ellipses because the synergies, by coupling muscles, also couple two important stiffness characteristics: the stiffness ellipse’s shape and orientation. That is, in the presence of synergies, as just described, there is only one free parameter that can be varied to control these characteristics, aelbow/ashoulder. Therefore, changing orientation independently of shape is impossible.In the presence of these synergies, one parameter suffices to change the orientation and shape of the endpoint stiffness ellipse: the ratio of elbow synergy activation to shoulder synergy activation, aelbow/ashoulder) over a range of 2 orders of magnitude (1/10 to 10) to see how much the orientation of the ellipse is able to change.To further explore this coupling of task constraints by synergies, we vary the ratio of shoulder synergy activation to elbow synergy activation and the endpoint stiffness has a given desired shape and orientation, as in In the absence of synergies in our model , we can determine if the arm is able to meet the constraints thatThen if the feasible activation set begins as a 3-dimensional unit cube in the positive octant.The constraint of zero endpoint force is a 2-dimensional plane in activation space passing through the origin. This is because endpoint forces have a minimal value of 0 at zero activation).The constraint for desired endpoint stiffness of unity is also a 2-dimensional plane in activation space, but it does not pass through the origin. This is because muscle activation is required to produce stiffness: at the origin, there is no muscle contraction, therefore there is no muscle stiffness stiffness or endpoint stiffness.An illustration of these constraints, the existence of a solution, and the potential for energy minimization in the absence of synergies is illustrated in a1 = 2a2) results in an additional constraint plane that passes though the origin that will reduce the feasible activation set, reducing the dimensionality of the solution space. In this simple example, the dimensionality is reduced to zero—a unique solution [This geometric interpretation , 43, 44 solution , 43, 45.solution , synergiIn our 6-muscle model, the activation hypercube is 6-dimensional. The constraint of zero endpoint force is a 4-dimensional hyperplane in activation space passing through the origin  is realizable. We did this every 5° around the full range of orientations  and then checked the fraction of these orientations that are realizable. An example of the fraction of realizable orientations for all postures in the workspace is shown in The constraints in the realizability tests have five equality constraints Eqs  and 13. Our rationale for quantifying these ratios is that, for given observed stiffness ellipsoid in human subjects experiments, we want to know whether or not the central nervous system could minimize energy expenditure. If there is a large possible range of energies expended for a same endpoint stiffness ellipse, then it may only be possible for experimental means such as EMG to reach strong conclusions about energy minimization. But if the range is low, then EMG measurements may not have the resolution to reveal much additional information about energy expenditure (above the information obtained by only measuring the stiffness ellipse).−1 to 10. The arm endpoint is in a sample x − y position , where each link of the arm has length of 1. The area of the ellipses in To explore the effect of synergies in detail, we performed a more detailed analysis for a single posture. In that sample posture, The range of orientations is approximately 70°, which represents a realizable fraction of orientations of about 0.39. In this posture, shown in any orientation. Note the strong dependence on the posture of the arm . In general, the maximal possible energy reduction for many of the workspace postures for these stiffness ellipse shapes is low (10–30%), but can increase significantly to around 50% for some specific postures.The literature on muscle synergies is large and growing. There are already several papers debating their origins, advantages, and disadvantages , 42, 46.In the literature mentioned above, the origins of synergies as well as their specific structure and permanence continue to be debated. In their paper on static arm postures, Osu and Gomi (1999) mention that other arm synergies have been reported and that the regulation of muscle activation in static conditions seems to be quite different from that during movements. Nevertheless, this does not affect our main finding that synergies—regardless of their origin, structure or permanence—have important neuromechanical consequences in a variety of functional domains. This is because synergies imply a loss of control degrees of freedom . Therefore, the specifics of the synergies we chose to simulate as reported by Osu and Gomi do not affect the generality of our results. In fact, we went on to simulate five additional synergies as shown in Figs It is important to mention that comparing muscle coordination and stiffness regulation in static versus dynamic movement conditions may not be advisable—or even possible. This stems from the fact that the physics and neuromuscular physiology of the control of static force versus movement are inherently distinct and can even be incompatible; see , 48–50 aThe feasible activation set—i.e., all feasible neural commands to achieve a given task , 43, 44—This geometric approach uses a 6-muscle arm model with experimentally derived synergies to show that synergies severely constrain the ability to control the properties of the stiffness of the arm’s endpoint. Furthermore, it also shows reduction in the flexibility of energy consumption to implement them. That is, by reducing the dimensionality of the feasible activation set, synergies drastically limit the ability to orient the endpoint stiffness ellipse independently of its shape. The range of achievable orientations in the absence of synergies is already very sensitive to posture, but still allows significant energy minimization in some postures. Implementing synergies drastically reduces, and can even remove, the ability to minimize energy.Ks is the shoulder stiffness provided by co-contraction of the mono-articular shoulder muscles, Kb is the bi-articular joint stiffness provided by co-contraction of bi-articular muscles, and Ke is the elbow stiffness provided by co-contraction of mono-articular elbow muscles. This implies 3 constraints, and therefore 3 degrees of freedom for the system. However, our formulation without synergies has 4 degrees of freedom since only 2 constraints must be satisfied  of the endpoint of a simulated arm can be controlled in the presence or absence of muscle synergies. That is, the extent to which the endpoint of the limb would displace passively in response to a force perturbation in every direction. That stiffness is the product of the level of activation of each muscle, and the anatomy and posture of the limb. We assumed, as others have in the past, that the active stiffness of a muscle is linear and proportional to the maximal force a muscle can produce and the level to which it is activated. While the linearity of active muscle stiffness with respect to muscle strength and activation is likely not entirely realistic, we focused on the effects of the presence or absence of muscle synergies. Using a nonlinear relationship would likely produce different numerical results for the precise shape, size and orientation of stiffness ellipses. However, it would not overcome the limitations that muscle synergies impose because those limitations come about from a reduction of the number of individually controllable muscles. That is a matter of scale rather than quality. Future work should naturally explore whether or not more realistic physiological mechanisms for muscle stiffness exacerbate the effects of synergies—particularly in neurological conditions. In addition, this model is limited in that it does not take into account passive muscle stiffness, reflexive stiffness, or feedback pathways, which can clearly be used to minimize energy further depending on the frequency content of a perturbation or motor noise during a task. It has been suggested  that somA subtle but important issue is that studying symmetric endpoint stiffness does not take away from our findings, bur rather enhances our result about the functional limitations of synergies. Adding a net endpoint force (or torque) deforms the symmetry of endpoint stiffness, but it also further constrains the range of stiffness modulation. Balasubramanian and colleagues have made this point well by indicating that defining an endpoint force imposes an additional set of functional constraints that compromise the modulation of endpoint stiffness . SimilarOur model, like many others used to study arm stiffness , 13, 37,Our results suggest ways in which future high-dimensional models and arm stiffness experiments may be conducted to analyze stiffness synthesis strategies used by the CNS such as synergies, energy minimization, posture adjustment, and active reflex pathways. Reaching experiments could test stiffness ellipses in various postures during the reaching movement, since stiffness ellipsoid orientation flexibility is very sensitive to small changes in posture. Findings that conflict with the results of such a study could be analyzed in more detail as this would suggest significant feedback pathways that were developed as a result of motor learning and neural plasticity. More research into muscle synergies will help elucidate existing mysteries of neuromuscular control and empower improved mechanisms for therapeutic interventions for neuromuscular disorders in aging and disease.More generally, to our knowledge, this is the first study of the neuromechanical and energetic consequences of using synergies while meeting the multiple and compounding force and stiffness constraints that define tasks in the real world, particularly important for unstructured environments. As pointed out previously e.g., , 45, 47), 4745, 4An objection to the strength (though not to the substance) of this conclusion is that having many more muscles will naturally allow the implementation of synergies without such a drastic reduction of the feasible activation set. We agree with this interpretation as we have argued that thinking of vertebrates as having ‘too many’ muscles is paradoxical with evolutionary biology and clinical reality. That is, we have barely enough muscles for versatile and robust function in the real world , 45, 47.Set the necessary endpoint stiffness size, shape and orientation Specify the direction, speed and duration of the movement Control for the desired endpoint forces and torques Consider the influence of motor noise α-motoneuron pools to produce the necessary joint torques as per the classical muscle redundancy force-sharing problem α-motoneuα-motoneuron pools across shortening and lengthening muscles [Coordinate reciprocal inhibition of  muscles γ-drive and/or inhibit the stretch reflex in muscles undergoing eccentric contractions γ-drive aMediate interneuronal interactions Satisfy the temporal constraints of conduction velocities, muscle excitation-contraction dynamics, and activation/deactivation time constants  to ensurMore generally, every modeling study must assess its generalizability to everyday life—especially models with a relatively small number of joints and muscles. In such simplified systems, a few constraints may suffice to artificially deplete the system of its control degrees of freedom. The question then becomes whether, in models with many more muscles, the achievable stiffnesses are ‘good enough’ for the usual, day-to-day operation of the limb; and if so, from the functional perspective this reduced flexibility may not really be a disadvantage at all. We and others have debated this important issue in the contexts of muscle redundancy for the production of static forces, unimpeded limb motion, and their combinations , 54, 55.This compounding of multiple, potential conflicting, spatial and temporal constraints naturally leads to a dramatic shrinking of the set of feasible neural commands for natural movements even when we have many muscles. This line of thinking helps clarify the apparent and longstanding paradox between the classical concept of muscle redundancy and the clinical reality of motor development and dysfunction . For exaIn spite of the simplified model used in the prior literature and here, our results nevertheless add to current thinking about endpoint stiffness in two critical ways. First, they enable us to explore the specific task-level trade-offs associated with specific synergies. And second, they show that there is a natural limit to how generalizable and flexible any synergy can be. Simply said, every synergy that is prescribed will reduce the feasible activation set (and thus the set of feasible actions) as strictly as the mechanics of the limb or the constraints of the task.Thus if one is to prescribe synergies to meet the multiple constraints of the many tasks we face in real life, how many synergies should one learn? The idea that each prescribed synergy solves, by construction, a well-defined control problem is well studied in the control literature , 65, 66.S1 Dataset(XLSX)Click here for additional data file.


Dear Colleagues,As you probably know, significant concern has developed over the irreproducibility of published results, and the NIH has expressed serious concern over this problem , 4.There is no real worry that this is due to scientific misconduct. Rather, it is believed to be due to poor training of investigators in experimental design, lack of reporting of methodologies in published papers, lack of critical evaluation and reviewing, and lack of publications on negative data or on critiquing others’ methods. Other forces such as various kinds of bias presumably contribute to this as well. There are a number of papers on this topic and I cite a few that may be helpful , 3, 4, 5Preclinical studies are more of a concern than clinical studies, where standardized reporting procedures exist and where there is more rigorous design and oversight . The useObviously, something must be done, and it is being done. The NIH is developing a number of initiatives, some of which will become mandatory in NIH sponsored training programs. There will be specific training opportunities with an emphasis on good experimental design. A checklist will be developed for reviewers and evaluators that address experimental procedures such as sample size calculations, randomization, blinding and so forth. Access to raw data and increased transparency will be addressed. Other groups in the scientific community will have to participate as well. These groups will include journals, private granting agencies, various review panels, and others.Journal of Drug and Alcohol Research (JDAR) has not had a problem with irreproducible results, but it is not a problem that can be ignored. I write this letter because this is a significant issue that is not going away. Correcting this problem can only be a good thing. This journal will support efforts to improve reproducibility, and will judiciously follow recommendations made by responsible groups. It seems reasonable to suggest that readers and submitters follow this topic and the recommendations from the NIH and elsewhere. Everyone—authors, editorial staff, readers, and reviewers—want JDAR to be a solid and trustworthy journal.


Chronic Achilles tendon tears could hinder patients and represent a challenge to surgeons. Although many different surgical techniques have been proposed for reconstruction of a neglected Achilles tendon rupture, there is no clear evidence to support one technique over the others, but the use of a technique that could allow for an “anatomical” reconstructions seems desirable.The present paper describes a new anatomic Achilles tendon reconstruction for chronic tears, using a quadriceps tendon autograft as graft source, with PRP injected into the graft and the neighbor tissue, and fixation in a bone trough with a simple small fragments screw.Autologous quadriceps tendon graft seems an excellent option, although -surprisingly- has received little attention until now.Autologous Quadriceps tendon graft (in bone-tendon configuration) is a simple technique that could allow surgeons to reconstruct tissue defects in the Achilles tendon with non-expensive hardware. Achilles tendon ruptures represent the most common acute tendon rupture in the human body, and frequently they are diagnosed solely based on clinical examination, but it is considered that up to 25 % of them can be misdiagnosed by the first clinician who examines the patient , 2. SomeIn the past, several authors –7 recommAlthough platelet rich plasma (PRP) has been used with success in the treatment of acute Achilles tendon ruptures , a literThe present paper describes a new and simple surgical technique to obtain an anatomic Achilles tendon reconstruction, using a quadriceps tendon autograft as graft source, with PRP injected into the graft and the neighbor tissue, and fixation in a bone trough with a simple small fragments screw.The patient is positioned in lateral decubitus position, on the uninjured side, tilted ventrally. Either general or regional anesthesia could be used, and prophylactic antibiotic in injected before thigh tourniquet is inflated. The lower limb is prepped and draped free. By external hip rotation with both the hip and the knee flexed, the assistant keeps the limb in a position in which the that the patella is pointing to the ceiling.A 5 cm skin incision is usually enough to delineate and harvest the bone-tendon quadriceps graft, with the standard technique. Usually, a 1 cm wide graft, with a 12 mm long bone plug and a 8–9 cm tendon length is obtained. After skin closure, the patient is rotated to ventral decubitus, which can easily be done without changing drapes. In this position, the Achilles tendon to be operated is now pointing to the ceiling, and the surgeon can work in a comfortable position.A standard paramedial Achilles incision, extended distally over the calcaneus tuberosity, is used. Careful dissection of the sural nerve is performed, taking into consideration the possibility that scar tissue or edema could be found surrounding it. After necrotic and scarred tendon tissue are debrided, a trough is created in the posterior aspect of the calcaneus, to accommodate the bone plug from the patella, and the plug is fitted into the trough and secured with a 3.5 mm cancellous screw Fig. . Next, tAfter surgery, the patients are inmobilized with a below-knee cast for 3 weeks, and an orthesis with range of motion control is used thereafter, allowing free plantarward motion but limiting dorsiflexion to −20° for the next 2 weeks while allowing partial weight bearing. The orthesis is retired for night rest and physiotherapy, avoiding dorsiflexion above neutral until the 8th postoperative week.The main finding of this study is that autologous quadriceps bone-tendon graft offers an excellent option for the repair of chronic Achilles tendon ruptures.Quadriceps bone-tendon graft allows the repair of the Achilles tendon defect without any deleterious effect on neighbor structures, while offering an “anatomical” repair, as the bone plug can be placed in the tendon footprint at the posterior aspect of the calcaneus, avoiding modifications in the traction vector of the tendon. To the best of our knowledge, however, no surgical method using a quadriceps tendon graft fixed in a bone trough at the anatomical insertion site of the Achilles tendon at the calcaneus can currently be found in the literature. The reason for developing this new method was to bridge the tendon gap using a fairly simple procedure with a graft that is commonly used by sports surgeons, and to avoid the use of local tendons, as this option is not free of complications and possible functional imbalances .Achilles tendon ruptures seem to have increased during the last two decades , probably due to the increase in the general population activity and sports participation . A seconOne of the most populat grafts for chronic Achilles tendon reconstruction is the FHL tendon, due to its proximity to the Achilles tendon, but its average lenght when harvested through a posterior incision is only 5.16 cm, which could prove insufficient to cover a higher defect , and forAfter surgery, the foot is placed in equinus position to reduce the tension in the graft tissue and to increase skin vascularization, in order to minimize the risk of skin necrosis . The useLimitations of this procedure lie basically in the distance of the tendon gap from the calcaneus: if is located more than 5–6 cm away from the calcaneus, the quadriceps graft might not have length enough to bridge it, in which case should opt for a different surgical procedures, as the ones recently described with a free tendon graft, as suggested by Sarzaeem  and MaffAutologous Quadriceps tendon graft (in bone-tendon configuration) is a simple technique that could allow surgeons to reconstruct tissue defects in the Achilles tendon. It could be used not only in cases of chronic or neglected Achilles tendon ruptures, but also in cases of surgical complications (as deep infections or Achilles tendon necrosis), without altering the function of the neighbor structures, nor shortening the myotendinous triceps surae unit.Written informed consent was obtained from the patient for the publication of this report and any accompanying images.


Many GABAergic interneurons are electrically coupled and in vitro can display correlated activity with millisecond precision. However, the mechanisms underlying correlated activity between interneurons in vivo are unknown. Using dual patch-clamp recordings in vivo, we reveal that in the presence of spontaneous background synaptic activity, electrically coupled cerebellar Golgi cells exhibit robust millisecond precision-correlated activity which is enhanced by sensory stimulation. This precisely correlated activity results from the cooperative action of two mechanisms. First, electrical coupling ensures slow subthreshold membrane potential correlations by equalizing membrane potential fluctuations, such that coupled neurons tend to approach action potential threshold together. Second, fast spike-triggered spikelets transmitted through gap junctions conditionally trigger postjunctional spikes, depending on both neurons being close to threshold. Electrical coupling therefore controls the temporal precision and degree of both spontaneous and sensory-evoked correlated activity between interneurons, by the cooperative effects of shared synaptic depolarization and spikelet transmission. •Double patch-clamp recordings from Golgi cells reveal millisecond synchrony in vivo•Millisecond synchrony requires gap junctions and is enhanced by sensory stimuli•m equalization and fast spikelet transmissionGap junctions drive synchrony via slow V•Modeling shows these findings can be generalized to any electrically coupled neurons van Welie et al. show using double patch-clamp recordings that cerebellar Golgi cells display millisecond precise correlated activity in vivo, which is enhanced during sensory processing. Gap junctions mediate precise correlated activity via slow membrane potential equalization and fast spikelet transmission. The cerebellum is thought to play a central role in governing the timing of movements. To understand how the cerebellum mediates temporally precise motor control, we need to understand the mechanisms underlying temporal coding in the cerebellar circuitry . VariousThe granule cell layer forms the input layer of the cerebellar cortex and receives mossy fiber inputs conveying sensory and motor information that are integrated by two cell types: the excitatory granule cells and inhibitory Golgi cells. Golgi cells locally inhibit the excitatory granule cells and each other . They haIn common with many other interneuron types  in the mWe have therefore investigated the functional role of electrical coupling in the Golgi cell network in anaesthetized mice in vivo. Using targeted dual patch-clamp recordings from Golgi cells, we reveal that nearby Golgi cells display robust correlated activity with millisecond precision that is dependent on electrical coupling. Electrical coupling mediates this precisely correlated activity by the cooperative effect of two mechanisms: by equalization of the subthreshold membrane potential and by direct spike-to-spike transmission via spikelets. This precisely correlated activity is further enhanced when sensory stimuli are used to evoke spiking, even though spikes driven by sensory input display broad temporal variation due to the integration of sensory-evoked synaptic inputs. These results suggest a role for precisely correlated activity in Golgi cells in cerebellar function and provide a template for understanding correlated activity in electrically coupled interneuron networks across the mammalian brain.To establish whether Golgi cells exhibit correlated activity in vivo, two-photon guided targeted loose cell-attached recordings A were maTo test the contribution of electrical coupling to precisely correlated Golgi cell activity we crossed connexin36 knockout (Cx36-KO) mice with GlyT2-EGFP mice see . ConnexiTo determine the mechanisms by which electrical coupling controls precisely correlated activity in vivo, dual whole-cell recordings were made from neighboring Golgi cells A. Most nThe raw data in both current and voltage clamp B show thWe next computed cross-correlograms of individual EPSC event times and determined the percentage of precisely synchronous EPSCs between coupled neurons. Only a small fraction of the EPSCs  computed from cross-correlations were precisely synchronous (defined as occurring within ±0.5 ms), as reflected in the small peak (z score of 6 ± 4) in the normalized cross-correlogram at 0 ms F. These Slow subthreshold membrane potential correlations mediated by coupling may be permissive for correlated activity, but they do not explain the millisecond precision of the correlated activity we observed. We therefore set out to test whether transmission of a spike via gap junctions and the resulting “spikelet” currents can trigger millisecond precision correlated activity. First, we examined the amplitude of spikelet currents and potentials by computing spike-triggered averages in simultaneous whole-cell and cell-attached recordings A. This rVm, –41.8 ± 1.4 mV for correlated spikes and –43.9 ± 1.7 mV for noncorrelated spikes, n = 5, p = 0.01, Vm, 1.5 ± 0.4 mV for correlated spikes and 0.5 ± 0.1 mV for noncorrelated spikes, n = 5, p = 0.02, Vm was positive, Spikelet potentials are small, and thus, to determine how spike-to-spike transmission across gap junctions may depend on the membrane potential in the postjunctional cell, we analyzed the membrane potential 5 ms prior to a correlated spike triggered by a cell-attached spike in its coupled neighbor and compared it to the membrane potential on those occasions in which a correlated spike failed to be induced D. This rTo test directly whether spikelets can trigger postjunctional spikes, we triggered spikes by current injection in one cell of a coupled pair (recorded in whole-cell mode) while recording the spiking of the other cell (in cell-attached mode). A train of spikes in the prejunctional cell led to a robust increase in spiking of the postjunctional cell . Given that the AHP has been predicted to cause desynchronization of neurons , we modiFinally, we determined the degree and temporal characteristics of correlated activity in coupled Golgi cells in response to sensory stimulation. Since mossy fiber terminals conveying sensory stimuli terminate profusely in the granule cell layer and may simultaneously activate many coupled Golgi cells, precisely correlated activity between Golgi cells may be enhanced by a sensory stimulus. Alternatively, sensory stimuli might desynchronize or lessen the degree of correlated activity . FurtherIn simultaneous recordings from pairs of Golgi cells, sensory stimulation triggered spiking in both cells  among Golgi cells , presumaOur simulations using a generalized mathematical model of dendritic electrical coupling reveal further insights into the biophysical mechanisms of correlated activity. While the spikelets are responsible for the millisecond precision of correlated spiking, subthreshold membrane potential equalization due to coupling acts cooperatively with spike-to-spike transmission to ensure the robust degrees of correlated spiking as observed experimentally. Moreover, they show that precisely synchronous synaptic inputs to Golgi cells are only likely to dominate millisecond correlated spiking if they represent more than 80% of all inputs. This emphasizes the dominant role of electrical coupling in determining precisely correlated activity of Golgi cells. Our simulations furthermore reveal that these effects are largely independent of spike shape. The reduced model used in the simulation exhibits passive dendrites, as has been experimentally observed for Golgi cell dendrites , like thRecent experimental work in cerebellar slices  and theoThe mechanism for millisecond precision correlated activity among electrically coupled interneurons we describe is simple and robust, and is likely to be widespread across the mammalian brain, given that electrically coupled interneurons can be found in many brain areas  and haveNevertheless, the importance of electrical coupling in cortical circuits has long been recognized at the level of network activity, where it contributes to and enhances oscillatory activity. For example, elimination of electrical coupling in Cx36-KO mice has been linked to slower theta oscillations in the hippocampus , as wellThe subthreshold membrane potential correlations combined with spike-to-spike transmission between Golgi cells ensure strong and precisely correlated activity in the face of spontaneous synaptic background activity. Furthermore, strong sensory-evoked bursts of synaptic inputs that drive spiking in individual cells enhance this precisely correlated activity. This correlated activity effectively serves to distribute MF and/or parallel fiber inputs throughout the coupled Golgi cell network, resulting in enhanced inhibition of downstream granule cells. It is known that tonic inhibition strongly determines the excitability and sensory responses of granule cells . TemporaThe ability to generate correlated inhibitory activity suggests that precisely timed feedforward inhibition  and “timOur data provide a mechanistic understanding of how electrical coupling causes correlated spikes in electrically coupled interneurons with millisecond precision in the context of the spontaneous and sensory-evoked synaptic drive in vivo. Importantly, the mechanism we describe should be relevant to most electrically coupled neurons in the brain, as it is generic and independent of spike shape. This suggests that electrically coupled interneurons will spike together with millisecond precision irrespective of the exact temporal structure of common synaptic input. Our results provide further support to the idea that electrical coupling is crucial for temporal computations performed in mammalian neural circuits.Please see Simulations were performed using NEURON 7.1 . Two redI.v.W. performed all experiments and analyses with the exception of the single whole-cell recordings of sensory-evoked responses and their analyses, which were performed by S.S.H. and S.K. The simulations were performed by A.R. The study was designed by I.v.W. and M.H., who also wrote the paper.


For more than forty years, graftectomy has been the standard treatment of spontaneous renal transplant rupture. However, recent evidences suggest that graft salvage strategies can be safely pursued, even in difficult cases.We report on a thirty-nine-year-old woman who received a deceased donor kidney transplant and experienced spontaneous allograft rupture due to acute rejection. The rupture was further complicated by urinary leakage. The kidney and the ureter were successfully repaired. Eight years after transplantation, graft function is still excellent.Due to the lack of transplantable organs and the long time usually spent on the waiting list, graftectomy should be only considered in case of refractory haemodynamic instability or compromised graft viability. Spontaneous renal allograft rupture is a rare but life threatening complication of kidney transplantation. Graftectomy is the safest option. However, if the patient can be stabilised, graft repair should be always considered because of the long waiting list and the low chance of receiving a second transplant.To the best of our knowledge, this is the first report on a patient who had her transplant saved after experiencing acute rejection, spontaneous graft rupture and urinary leakage.A thirty-nine-year-old woman with end stage renal disease secondary to eclampsia was admitted to our institution for her primary deceased donor kidney transplantation on January 2006. Pre-transplant comorbidities included hypertension, dyslipidemia and secondary hyperparathyroism. The donor was a twenty-six-year-old male who died from acute obstruction of the foramina of Monroe. Cold ischemia time was ten hours. The kidney was medium-sized, had one artery, one vein and one ureter. The donor and the recipient were blood group compatible and six HLA antigens mismatched. The highest recipient Panel Reactivity Antibody was 15 % and the direct microcytotoxicity crossmatch was negative. Macroscopically, the kidney looked normal. It was extraperitoneally transplanted in the left iliac fossa, as standard procedure. After declamping, the organ reperfused immediately. The graft ureter was anastomosed to the bladder according to the single stitch technique. The patient was enrolled in a phase III randomized, multicenter, clinical trial and received basiliximab , cyclosporine , everolimus  and steroids.The early post-operative course was complicated by delayed graft function requiring haemodialysis. According to the protocol, her baseline immunosuppression was not changed. Daily ultrasound evaluation showed a well-sized graft with no fluid collections, no hydronephrosis, and good intra-parenchymal flow. Haematologic and coagulation profiles were normal.On post-operative day four, the recipient suddenly complained of abdominal pain and the urinary output dropped. Blood pressure, pulse rate and haemoglobin concentration remained stable. Four hours later, the abdominal pain increased and the area over the graft became distended and tender. Hypotension rapidly developed, the pulse rate increased and the patient became anuric. Aggressive resuscitation was promptly initiated. An urgent Doppler ultrasound scan was performed. It showed a large hypoechoic collection surrounding the graft with good flow in the renal artery and a patent renal vein. Subsequent contrast-enhanced CT scan revealed a ruptured graft and a massive retroperitoneal haematoma with active bleeding from the transplanted kidney Fig. . The patOn post-operative day fifty-two, clear fluid started to seep from the wound. Urgent CT scan showed a large 5 × 2.3 cm) fluid collection in continuity with the area of the previous rupture (Fig. .3 cm fluEight years after transplantation, the patient is doing well and her serum creatinine is 1 mg/dL.Spontaneous renal allograft rupture is defined as a laceration of the renal capsule when there are no other identifiable injuries noted at the time of the organ retrieval . Its incSeveral causes have been proposed –3, 5–7. In case of haemodynamic instability, immediate surgical exploration is mandatory. Initial reports of conservative management of graft rupture showed poor results, with less than 30 % success rate. Failure to control acute bleeding, inability to reverse acute rejection, post-surgical development of multiple organ failure and uncontrollable coagulopathy were the main causes of the high rate of graft nephrectomies observed. In the last decades, improved surgical technique and post-operative care have significantly reduced transplant-related mortality and morbidity. Complex operations are now safely performed with good results. Current reports demonstrate that ruptured grafts can be saved with a success rate as high as 80 %. Moreover, recipients undergoing successful repair have long-term outcomes similar to the general transplant population. Recurrent rupture, the most dangerous complication of graft repair, only occurs in 5 % of patients and does not significantly jeopardise the prognosis (see Table When spontaneous renal transplant rupture occurs, nephrectomy is justified only in case of refractory haemodynamic instability or compromised kidney viability. When irreversible graft damage can be ruled out and the patient can be readily resuscitated, transplant salvage should always be attempted.Written informed consent for publication of this Case report and any accompanying images has been obtained from the patient. A copy of the written consent is available for review by the Editor of this journal.


What is the feeling of the editors of a medical journal when it reaches the significantmark of 1,000 published new scientific articles?On this occasion, the editors and reviewers looking back about what meant these 1,000papers published in the period of 27 years, from 1986 to 2013, confirms that they workedvery hard to reach this target. Let suppose, if each article has at least 1,000 words,1,000 articles addressing all possible issues related to digestive surgery will reach amillion words, and this amount certainly corresponds to an encyclopedia!1. And in thepresentation of a new journal he emphasized that: "This surgical breakthrough resulted inthe publication of many scientific articles and editing books and journals. But even so,due to the majority of surgical patients are in Gastrointestinal Surgery area, there arefew specialized sources to disseminate up the new information. For some time we have beenconsidering publishing a journal dedicated to this specialty, with articles by Brazilianand foreign authors to be distributed abroad, as well as in Brazil. Since English iscommonly used in medical and scientific specialties, would be published in bothlanguages".The first article published in 1986 was written by the creator and founder of the BrazilianArchives of Digestive Surgery (ABCD), Prof. Dr. Henrique Walter Pinotti, aboutsurgeonpatient relationshipProfessor Pinotti, in his speech at the beginning of the activities of the BrazilianCollege of Digestive Surgery (CBCD ) in 1988 emphasized that : "With education we not onlyinform, but we forge high level professionals, which can develop their knowledge, applyingcorrectly their resources and thus able to benefit the patient. Knowing the limits of theircompetence, he will be able also to serve his patient avoiding the worst result of surgery,which is the iatrogenesis. Our College, in education, should develop the spirit that everyperson who wants to teach must have, and also finding the ones that want to learn. And thesuccess achieved in the safe training can constitute stimuli for new frontiers ofknowledge".2.And, undoubtedly, both ABCD and CBCD opened new doors to knowledge and have contributed tomedical education in the country.During all these years, since the publication of the first issue of the ABCD, many changesand advances occurred in medicine in general, in the digestive surgery and general surgery;new methods have emerged, in the preoperative and the postoperative care and also in therelationship between surgeon-patient3. Later, in 2013, theSobracil (Brazilian Society of Videosurgery), was another association that came toincorporate the ABCD as its official journal for scientific papers.In 2009 the journal was accepted and included in the list of national journals indexed inSciELO (Scientific Electronic Library Online), came to be published in Portuguese andEnglish, getting so more visibility, more value and, as already is accessed online, isvisible for consultation worldwide through internet, thus raising its impact. In addition,in 2010 also was made an agreement with other surgical associations, and ABCD also becamethe official organ for scientific publication of the Brazilian Gastric Cancer Association,the Brazilian Chapter of the International Hepato- Biliary-Pancreato Association, StudyGroup of Pancreatic Diseases and the Brazilian Society of Metabolic and BariatricSurgery4.From 2012, it was with great pride that the publishers of the ABCD communicated to allmembers and researchers of the related areas  itsinclusion in the MEDLINE/ PUBMED. Therefore, the journal will be a Brazilian vehicle tocompete with the best journal in the world. ABCD, with these indexations, can positivelycontribute with the international ranking of Brazilian publications, climbing one more stepin the number of publications on worldThe feeling is of great satisfaction and accomplishment towards Brazilians surgeons, tomembers of the Brazilian College of Digestive Surgery and to the society in general. Ajournal that published 1,000 papers, all submitted to review of their referees and editorsin regard to their ethical and scientific content, bilingual writing - Portuguese andEnglish -, with results and conclusions, with good recommendations and with orientativefinal messages, certainly, have reached its maturity. We understand that the journal gotgreater visibility and even greater national and international accreditation; got higherquality in intellectual production; the authors were more valued in their scientific fieldand, as a result, they submitted higher number of papers to ABCD, contributing to increaseoverall national publications.In this opportunity we have to thank the authors and coauthors who believed and sent theirarticles to us, contributing to the dissemination of this fantastic and important amount ofknowledge with quality and to the ones who believed in the progress of the journal. We haveto thank the Postgraduate Programs (strict sense) recommended by CAPES, who submitted theirselected studies for publication and to all the editors and researchers who, directly orindirectly, contributed to the journal be even better. We must also to thank the graphicpublisher Comunicare that contributed with professionalism and expertise on printing andfinishing most part of ABCD existence, as well as the graphic design made by Bruno Ariedecannot be forgotten in this celebration.In 2014, we will start the electronic submission and internal flow online of the articles,and a new website specially created to the journal, giving more professionalism to thewhole process and facilitating the authors.Finally, we must dream to aspire growing, to achieve victories and success; to do so, allof us must have a lot of dedication, great effort and, importantly, with a strong workteam!


Journal of Neonatal Surgery, the premier quarterly, peer-reviewed journal focusing on surgical conditions of the neonates, celebrated the completion of its second volume with the publication of the Sept-Dec 2013 issue. It is the first journal of its kind, serving as an international forum to disseminate the knowledge about neonatal surgery and its allied subjects. The growth and interest sparked during the first two years of publication has been remarkable. We have maintained the initial excitement and published every issue on time.Last year, the Journal received 57 manuscripts from around the world of which 52 were accepted for publication. The top five manuscripts that had highest viewership in the year 2013 are listed below. We congratulate each of their authors.Saifullah M, Ferdous KMN, Shahjahan M, Sayed SA. Management of Congenital Talipes Equino Varus (CTEV) by Ponseti Casting Technique in Neonates: Our Experience. . J Neonat Surg. 2013; 2: 17 (3051 views)Celayir CA, Sahinoglu Z, Selcuk S, Moraliglu S, Bosnali O. Unilateral Huge Hydronephrosis Necessitating Fetal Interventions (2060 views)Krishnan L. Pain Relief in neonates J Neonat Surg. 2013; 2: 19. (971 views)Patel RV, Kumar H, More B. Preampullary duodenal web simulating gastric outlet obstruction. J Neonat Surg. 2013; 2: 13. (927 views)Haidar AM, Gharmool BM. Extracorporeal testicular ectopia through inguinal canal: a case report. J Neonat Surg. 2013; 2: 10. (726 views)It is very interesting to note that the maximum viewership this year was for an original article on a musculo-skeletal anomaly (read orthopedic) from none other than a center in Bangladesh. We once again wish to express my sincere gratitude to our reviewers for their valuable time, as well as to our authors and the Journal's Editorial Board for their most valuable support. On its second anniversary, we suggest that we consider launching a formal society associated with the journal. We would be looking forward to hear the views of the editorial board and all-important readership in this regard. Indexing with Pubmed is in pipeline. We also wish to infuse some fresh blood in the Editorial Board. We invite applications from our worthy global colleagues for the honorary positions on the Editorial Board. We trust our faithful readership would keep supporting us in our academic endeavor.Source of Support: NilConflict of Interest: None


Models allowing for continuous heterogeneity by assuming that value of one or more parameters follow a specified distribution have become increasingly popular. This is known as ‘mixing’ parameters, and it is standard practice by researchers - and the default option in many statistical programs - to base test statistics for mixed models on simulations using asymmetric draws .This paper shows that when the estimated likelihood functions depend on standard deviations of mixed parameters this practice is very likely to cause misleading test results for the number of draws usually used today. The paper illustrates that increasing the number of draws is a very inefficient solution strategy requiring very large numbers of draws to ensure against misleading test statistics. The main conclusion of this paper is that the problem can be solved completely by using fully antithetic draws, and that using one dimensionally antithetic draws is not enough to solve the problem.A second point of the paper is that even when fully antithetic draws are used, models reducing the dimension of the mixing distribution must replicate the relevant dimensions of the quasi-random draws in the simulation of the restricted likelihood. Again this is not standard in research or statistical programs. The paper therefore recommends using fully antithetic draws replicating the relevant dimensions of the quasi-random draws in the simulation of the restricted likelihood and that this should become the default option in statistical programs. JEL classification: C15; C25. Models allowing for continuous heterogeneity have been developing rapidly thanks to advances in computational speed and understanding of simulation methods for approximating integrals, see e.g. . One wayMany models are estimated by simulated maximum likelihood, and restrictions easily tested using Likelihood Ratio tests. As an example, the Mixed MultiNomial Logit MMNL,  is now aThis paper illustrates that if the conventional likelihood is symmetric the simulated mixed likelihoods will always be symmetric, but if the conventional likelihood is asymmetric this is not true unless the draws for the Quasi-Monte Carlo integration are also symmetric around zero. Antithetic draws have been suggested as a variance reduction technique for Monte Carlo integration of asymmetric functions, especially for Bayesian inference see e.g. . HoweverAntithetic Halton draws have also been suggested as an instrument for faster computation of Quasi-Monte Carlo integrals, allowing for more precise point estimates within a reasonable time frame  which are caused by the asymmetry; it does NOT solve the problem of ‘true’ local maxima  which can occur as a result of a non-linear utility function, or insufficient data. We also show that the same mechanisms appear in a real data set with invalidating implications for Likelihood Ratio tests.Using data simulated under a Mixed MultiNomial Logit model specification, we illustrate how asymmetry of the simulated likelihood function causes the likelihood to depend on the signs of the estimated Choleski factorization, and that n to n-1 most standard procedures simply estimate the restricted model using the n-1 first set of quasi-random draws, irrespective of which of the n original dimensions is restricted. As illustrated in this paper, keeping track of which dimension is restricted, and removing exactly this dimension when estimating the restricted model, may lead to better Likelihood Ratio tests.Having solved the problem of inconsistent Likelihood Ratio tests caused by asymmetric draws, the paper turns to another problem which could still invalidate Likelihood Ratio tests, even when antithetic draws are used. When restricting the number of dimensions of the mixing distribution from The problem and solution presented in this paper not only applies to Mixed MultiNomial Logit models, but also to other models estimated by maximum simulated likelihood and the paper therefore provides a valuable contribution to the ongoing struggle to improve simulation methods. Halton draws are used in this paper, but the properties of the antithetic draws can be generalized to other types of draws.The structure of the paper is: The above section introduced the problems associated with Likelihood Ratio tests performed on simulated log-likelihood values, if these are simulated using asymmetric draws. The following theory section consists of a subsection which outlines the standard way of estimating and testing within panel Mixed MultiNomial Logit models, a subsection which explains why asymmetric draws used in Quasi-Monte Carlo integration of mixed likelihoods may invalidate Likelihood Ratio tests, followed by two subsections which first illustrate the problem on simulated data by comparing results in the true optimum using conventional Halton draws and then using real data. The method section introduces antithetic Halton draws. The results section also contains two separate subsections, one which presents the encouraging results of using fully antithetic of draws and another which introduces the second problem which concerns tests reducing the dimension of the mixing distribution. The final section concludes on both problems.As mentioned above this section consists of four subsections, which introduces the problem of inconsistent likelihood ration tests due to asymmetric draws.i, I is the number of individuals, θ. The likelihood function is maximized over θ.In a conventional logit  it is as becomes :(1)whereCalculating the likelihood function in Clearly, reliable estimation, validation and inference techniques are a prerequisite for sound models and analysis. The use of simulated likelihoods are bound to induce some approximation error, and it is therefore important to validate the results, e.g. by varying the starting values of the parameters and checking the stability of the results. One example of a simulation error is investigated in Many other types of quasi-random draws have been suggested and found to be more efficient than Halton draws, e.g. -nets In many cases the purpose of estimating a likelihood function is twofold: Maximizing the likelihood function leads to the set of parameters which fit the data best, and comparing the best likelihood values of different models makes it possible to infer whether the models are significantly different. The latter is done by Likelihood Ratio (LR) tests based on the difference between the restricted and the unrestricted likelihood values see e.g. . If the This paper however point to a very different and more serious type of variation in the value of the maximum log-likelihood. We find that the use of asymmetric draws for Quasi-Monte Carlo simulation of mixed likelihoods may lead to cases where the parameters of the statistical model are uniquely identified, but the maximum likelihood function varies, we call this ‘false’ local maxima, whereas ‘true’ local maxima varies both in likelihood value and parameter value. The absolute level of the log-likelihood function is of no interest, but if the difference in the value of the simulated log-likelihood given different starting values of the parameters is above e.g. two, testing hypotheses may easily lead to false conclusions. For a Chi-square distribution with one degree of freedom the critical value is 3.84 at the 5% level. This means that if the difference between the unrestricted and the restricted log-likelihood is above 1.92  the null hypothesis will be rejected at the five percent level in a test with one degree of freedom. The varying values of the log-likelihood function may first of all lead to falsely accepted or rejected hypotheses. Secondly, it may also falsely indicate that data are not informative enough to support the model, and therefore lead to unnecessary reductions in model complexity.variance rather than the standard deviation, and since the variance is the square of the standard deviation the true mixed likelihood function of the standard deviation will be symmetric around zero.If one parameter in a conventional logit model is mixed with e.g. the normal distribution, two moments characterizing the distribution are estimated, a mean and a standard deviation. When estimating the mean and the standard deviation of the mixing distribution, these are usually both maximized over the entire real axis R is the number of draws and the In most cases however, the true value of the likelihood value of a Mixed MultiNomial Logit model is not possible to obtain, and instead the value is often simulated using Quasi-Monte Carlo integration. This means that the value of the likelihood function of the conventional likelihood is calculated for a number of quasi-randomly drawn i, the rth draw is created asstdθ is the standard deviation of the mixing distribution, i and all r, and therefore:We choose to use the normal distribution as an example of a mixing distribution, which means that if the mixing distribution is one dimensional then for each individual p is symmetric in i, r and p is not symmetric in i and r there exists a value s so that i’s and r’s.If the conventional likelihood θ is not identical to the simulated mixed likelihood of This means that the simulated mixed likelihood of Q is the triangular Choleski factorization and QQ’ = n-dimensional mixing, the variance-covariance matrix may be obtained by 2n different Choleski factorizations with different combinations of signs of the elements of the triangular matrix. This means that if an asymmetric likelihood function such as the conventional logit model is mixed with a distribution which depends on a Choleski factorization of a variance-covariance matrix, using asymmetric draws, the combination of signs of the estimated Choleski factorization will wary between quadrants, but all lead to the same variance-covariance matrix. The values of the parameter estimates are therefore not affected by the lack of symmetry of the quasi-random draws, but the optimal value of the mixed likelihood may differ between the 2n quadrants. As shall be illustrated in the following section, this problem can in some cases invalidate Likelihood Ratio tests.If the mixing distribution is multivariate, the draws are created as 3 = 8, and the likelihood function must therefore be symmetric in all eight quadrants.In order to investigate the magnitude of the problem under controlled conditions, a hypothetical data set has been simulated. The data are panel data with 1,000 individuals each making 20 choices between 4 alternatives. The utility of the alternative specific constant is zero for the alternative which is used as base; the utility of the remaining alternatives follows a three-dimensional normal distribution with no correlation and nonzero means. In the case of three mixings, the variance-covariance matrix is estimated in optimized over each quadrant, but instead calculated by Quasi-Monte Carlo integration in the optimal point which is known because the data is simulated. The evaluation is done by Quasi-Monte Carlo integration, using standard Halton draws. In these calculations, the probability of finding an optimum in a given quadrant is treated as equal for all quadrants. In actual estimations the probability of ending up in a given quadrant may well vary, and the results in this section therefore only illustrate the magnitude of the problems that may potentially arise from actual estimations. As will be illustrated in section 0, estimations on actual data lead to results in all eight quadrants, so the problem also exists when the modes of the distribution of the mixed parameters are optimized rather than known a priory.One of the virtues of simulated data is that the true mean and variance-covariance of the mixing distribution are known. The finite nature of the simulated data means that the true  means and standard deviations of utility in the sample are not identical with the values used in the simulation of the data but in the rest of this section, the likelihood values will be evaluated in the true mean and variance-covariance of the simulated data for each of the eight quadrants, and compared between the different quadrants. The purpose of this section is to illustrate the potential problem using simulated data, ignoring the optimization errors caused by different optimization routines. We use therefore use the term ‘evaluated’ rather than ‘estimated’ because the likelihood function is not and standard deviation equal to zero. Testing whether the mean of alternative B is equal to zero is therefore not the same as testing whether the utility of alternative B is the same as the utility of the base alternative A.As mentioned above, one of the problems caused by the difference between the values of the log-likelihood function evaluated at different quadrants is that it influences the results of Likelihood Ratio tests. The rest of this section investigates the effect on a Likelihood Ratio test of the null hypothesis that the mean utility of alternative B is zero. Note that the base alternative A has both mean The large variation in the value of the log-likelihood function means that the value of the restricted model in one quadrant may be higher than the value of the unrestricted model in another quadrant, but never within quadrants. I shows the relationship between the two models in each quadrant and II ignores the quadrants and sorts the eight values by size. Especially from II it is evident that the value of the restricted model will sometimes be higher than the value of the unrestricted model, leading to negative values of the LR test statistic.same data set. Had the test been performed on different realizations of data with identical values of the mean and the variance-covariance, the test should have been accepted on 10 per cent of the data sets at the ten percent level, but when the tests are performed at the same dataset the results should all be identical. The differences are caused by the asymmetry of the Halton draws used in the Quasi-Monte Carlo integration of the likelihood, not by statistical properties of the test.The standard deviation of the p-values presented in optimized using 52 different sets of starting values. All calculations on real data are conducted in an extension of the MMNL GAUSS program developed by Train, Revelt and Ruud, which allows for correlation between mixed parameters. The antithetic Haltons are added to the program by the author of the present paper.The problem described above has also been experienced on real data. The example below is based on 10,971 observations from 848 individuals, choosing between four different alternatives. The data has been used to estimate willingness to pay for eggs with different levels of animal welfare . The restriction is now placed on the standard deviation of the utility of alternative C instead of the mean utility of alternative B, which was restricted in the mean-restriction case above. The utility of alternative C has a mean of 0.9981 and a standard deviation of 0.0984. The restricted model in this example assumes that the standard deviation is zero, but places no bounds on the mean. This means that the restricted model does not assume that the utility of alternative C is the same as the utility of the base alternative A. n-dimensional normal mixing is estimated by Quasi-Monte Carlo integration using asymmetric draws, the estimated variance-covariance matrix may be obtained from 2n different Choleski factorizations, located in different quadrants of the 2n dimensional parameter space, and these different factorizations may lead to different values of the optimized log-likelihood, even though they all lead to the same variance-covariance matrix. The paper shows that if the solution to an unrestricted and a restricted model is found in different quadrants, the Likelihood Ratio test is not reliable, and the paper also demonstrates that using fully antithetic draws eliminates this problem. The problem could also be solved by increasing the number of draws; but fully antithetic draws allows for faster computation and not least provides more reliable results for a given number of draws.This paper presents two problems which both mean that Likelihood Ratio test in mixed models estimated by standard methods cannot always be trusted. The first problem is that when a model with Halton draws and the normal distribution are used in this paper, but the need for fully antithetic draws will most likely also be relevant for other types of asymmetric draws, and for other types of distributions. As presented earlier, many other types of draws are used, but just like the Halton draws these are asymmetric. This paper shows that whenever the theoretical utility function is symmetric in one or more parameters  the draws used for Quasi-Monte Carlo simulation must also be symmetric. Other distributions - such as the triangular distribution and the log-normal distribution - also have parameters which can only be positive, and are therefore likely to suffer from the same problem as the normal distribution. Antithetic draws are therefore strongly recommended for future use in standard estimation procedures for mixed models.n-1 different optima which still may lead to false Likelihood Ratio tests. In the three dimensional mixings used in this paper, the dimension of the full set of antithetic draws is only eight and it is therefore possible to use fully antithetic draws, but in cases of higher dimensional mixings this may not be possible. In many applications the dimension of the mixing distribution will be small enough to use fully antithetic draws, and in these cases fully antithetic draws will ensure reliable Likelihood Ratio tests. Fully antithetic draws are therefore recommended for ‘small’-dimensional mixings.Some estimation procedures allow for one-dimensionally antithetic draws, but as explained above, one-dimensionally antithetic draws only removes one dimension of the problem, leaving 2The second problem illustrated in this paper is that even when fully antithetic Halton draws are used, testing restrictions on the number of mixed parameters may lead to false inference if the relationship between primes  and mixed parameters are not maintained in the restricted model. Again, the problem could also be solved by increasing the number of draws; but keeping track of base values for different dimensions allows for faster computation and not least provides more reliable results for a given number of draws.We therefore also recommend that for all types of quasi random draws, the user should be able to assign specific base values to specific dimensions, so that the set of base values can be maintained even when reducing the number of dimensions.Appendix S1(DOC)Click here for additional data file.


Development and Future Perspectives of Behavioral Medicine in JapanThe study of the “Type A behavior pattern and myocardial infarction” was one of the main themes in the early stage of Behavioral Medicine. After that, behavior modification came to be widely applied to the treatment of various kinds of chronic diseases, and a general concept of Behavioral Medicine was subsequently formed. The Japanese Society of Behavioral Medicine was established in 1992 and is comprised of researchers in the fields of clinical medicine, social medicine, and psycho-behavioral science. Recently, we devised a core curriculum for behavioral science and behavioral medicine and have published a Japanese version of the “Textbook of Behavioral Medicine” in conformity with it. It is a primer that includes all of the basics and clinical applications of Behavioral Medicine and is edited as a manual that can be utilized in clinical practice. We hope this book will contribute to the development of Behavioral Medicine in Japan, to a more healthy life for our people, and to the improvement of the QOL of our patients. In this paper, I discuss the future perspectives from my personal opinion while looking back on the history of Behavioral Medicine in Japan. The study of the “Type A behavior pattern and myocardial infarction” was one of the main themes in the early stage of Behavioral Medicine. Although Psychosomatic Medicine was based on an approach based on “character and disease” from a psychoanalytical viewpoint, the type A behavior pattern was recognized as a risk factor for myocardial infarction in the results of a large-scale predictive study . FurtherIn this paper, I discuss the future perspectives of Behavioral Medicine from a personal perspective while looking back on the history of Behavioral Medicine in Japan.In the Charter of the International Society of Behavioral Medicine (1990) , BehavioThe International Society of Behavioral Medicine was established in 1990 and an international conference has been held every two years since the first international conference was held in Uppsala University, Sweden. Table The Society of Behavioral Medicine was established in the United States in 1979, and interdisciplinary transaction between behavioral science and biomedical science has been subsequently promoted. Because the significance of behavioral medicine in the prevention, diagnosis, and treatment of chronic diseases has been recognized, basic medical research and clinical application into this field have progressed rapidly. In this setting, there were many predictive studies of the “Type A behavior pattern and myocardial infarction” in the 1960s and of the outcome of programs for the prevention of the recurrence of myocardial infarction by behavior modification from Type A to Type B.After the annual meeting of the Society of Behavioral Medicine was held in 1986, attended by many behavioral scientists and clinical practitioners from many countries of the world, the International Society of Behavioral Medicine was established in 1990 and currently has 26 member societies from around the world. The activity of the International Society of Behavioral Medicine includes scientific conferences, international education seminars, and publishing the “International Journal of Behavioral Medicine”. Prof. Kawakami took the position of president of the International Society of Behavioral Medicine from 2010 to 2012. Many Japanese members have played active roles in many committees. Prof. Tsutsumi is the chair of the scientific program committee for the Melbourne conference in 2016.As mentioned above, the 12th International Symposium at the University of Tokyo was an opportunity to stimulate Japanese behavioral scientists. The Japanese Society of Behavioral Medicine started with members integrated into 52 groups from the fields of clinical medicine (psychosomatic medicine), social medicine , and behavioral science (psychology). Its core members were Prof. Ikemi, Prof. Uchiyama, and Prof. Araki. Its activities included an annual meeting, education workshops, and publishing the “Japanese Journal of Behavioral Medicine”. We have continued to carry out unique activities as an interdisciplinary society and to participate actively in international conferences. Many Japanese members participate regularly in international conferences.In 2008, we hosted the 10th International Conference of Behavioral Medicine, which was highly evaluated for its scientific and management aspects by overseas core members. Table We revised some of the rules of the society in 2009, changing from a group participation system to a personal participation system and accepting many new members. In addition, we planned the activation of research activities by organizing many special interest groups (SIG). The number of members is now about six hundreds.In 2015, we published a Japanese version of the “Textbook of Behavioral Medicine”, which has been a long-pending objective since the establishment of the Japanese Society of Behavioral Medicine 25 years ago. Recently, behavioral science was included as an important subject for incorporation in our international medical education core curriculum. Also, the importance of behavioral medicine in clinic practice is increasing. Although many European textbooks have been published, there was no Japanese textbook on behavioral medicine. Therefore, we drew up a model core curriculum for behavioral science and behavioral medicine and wrote a textbook in conformity with the model.As showed in Table This textbook is a primer that includes all of the “basics and clinical applications of behavioral medicine” and that is written for use in various fields of education, such as medicine, nursing, and psychology, and as a manual that medical staff can utilize in clinical practice. I would like to emphasize that this textbook is very useful for understanding the relations between behavior and health and for treating patients with chronic diseases.We hope this textbook will contribute to the realization of more healthy lives for our citizens, to the improvement of the quality of life of our patients, and to the development of behavioral medicine.It is well known that psychosomatic medicine developed in the United States in the 1940s, as a psychoanalytical viewpoint toward somatic diseases that made much of the role in psychogenic theory. Since the Biopsychosocial Medical Model was proposed by Engel, GL (1977) , psychosOn a memorable occasion, Prof. Ikemi, one of the founders of the Japanese Society of Behavioral Medicine as mentioned above, excitedly told me “psychosomatic medicine and behavioral medicine are important pairs”. He had high expectations for the development of behavioral medicine in Japan. Japanese research into psychosomatic medicine is closely related to behavioral medicine. However, behavioral medicine is characterized as an interdisciplinary science field that includes social medicine and psycho-behavioral science in addition to clinical medicine as psychosomatic medicine.The Japanese Society of Behavioral Medicine is comprised of researchers in the fields of clinical medicine, social medicine, and psycho-behavioral science and performs interdisciplinary research activities. Our purpose is to contribute to the realization of a healthy society by investigating the associations between behavior and disease, the treatment and prevention of various chronic diseases, and the promotion of health. We intend to have scientific evidence on behavioral medicine included in the national health promotion policy known as Health Japan 21.As mentioned above, the Japanese Society of Behavioral Medicine is one of the main members of the International Society of Behavioral Medicine and our members perform international committee activities on education and research. We would like to encourage the participation of our Japanese Society of Behavioral Medicine members in worldwide scientific activity, especially by our young researchers. In the 21st century, which has been called “the times of stress” and “the times of the heart”, we are convinced that Psychosomatic Medicine and Behavioral Medicine continue to be important research fields that contribute to the welfare and health of the nation as “an important pair”. Although Psychosomatic Medicine has made many great contributions to clinical practice for patients with various psychosomatic diseases and stress-related diseases, Behavioral Medicine has the possibility to expand its findings to welfare worldwide. I hope the research activities of the association members into environmental factors and human health will be extensively promoted in the near future.I discussed the history and future perspectives of Behavioral Medicne in Japan. The Japanese Society of Behavioral Medicine was established in 1992 and is comprised of researchers in the fields of clinical medicine, social medicine, and psycho-behavioral science. As Japanese research into psychosomatic medicine is cosely related to behavioral medicne, both are important pairs. I hope the research activities of behavioral medicine will contribute to human health and welfare.


To the Editor:I read with interest the case report by Whitlow and Davis in the November 2014 issue of the Western Journal of Emergency Medicine regarding management of high altitude pulmonary edema (HAPE) in an experienced mountaineer.