Voluntary medical male circumcision (VMMC) reduces risk of HIV acquisition in heterosexual men by approximately 60%. As some countries approach targets for proportions of adolescents and adults circumcised, some are considering early infant male circumcision (EIMC) as a means to achieve sustainability of VMMC for long term reduction of HIV incidence. Evaluations of specialized devices for EIMC are important to provide programs with information required to make informed decisions about how to design safe, effective EIMC programs. We provide assessments by 11 providers with experience in Kenya employing all three of the devices most likely to be considered by various EIMC programs in east and Southern Africa. There was no one device that was seen to be clearly superior to the others. Each had its own advantages and disadvantages. Provider preferences were situation-specific. Most preferred the Mogen Clamp if they themselves were performing the procedure. However, most were concerned that not everyone will have the skills necessary for optimal safety. If someone else were circumcising their son, most would opt for the AccuCirc because of the risk of severing the glans when using the Mogen. A minority preferred the PrePex, but only if the baby received local anesthesia, not EMLA cream (a eutectic mixture of lidocaine 2.5% and prilocaine 2.5%), as presently prescribed by the manufacturer. In the context of a national EIMC program, all participants agreed that AccuCirc would be the device they would recommend due to protection of the glans from laceration and to the provision of a pre-assembled sterile kit that overcomes the need for additional supplies or autoclaving. All agreed that scaling up EIMC, integrating it with existing maternal child health services, will face significant challenges, not least of which is persuading already over-burdened providers to take on additional workload. These results will be useful to programmers considering introduction of EIMC services in sub-Saharan African settings. Male circumcision (MC) is a proven HIV prevention intervention, reducing the risk of heterosexual acquisition of HIV in men by 57–67% in three randomized controlled trials and in long-term follow-up studies –6. The WIn 2010, the WHO published the “Manual for Early Infant Male Circumcision under Local Anaesthesia ,” which Evaluations of specialized devices for EIMC are important to provide programs with the information required to make informed decisions about which devices fit different local needs. We here provide assessments by providers with experience employing all three of the devices most likely to be considered by various EIMC programs in east and Southern Africa. The providers compare the advantages and disadvantages of each device and give their informed opinions on which device would be best to use in different contexts, including as part of a large scale national EIMC program.This study was a discussion group conducted as part of a larger evaluation of the safety and acceptability of the AccuCirc device for EIMC. The participants were clinical officers, nurses, interviewers and mobilizers who had experience in provision of EIMC services with at least two of the three EIMC devices . The two interviewers and a mobilizer were included to gain their insights regarding cultural preferences, demand creation and mothers’ opinions about the procedure. The study participants were all employees of the Nyanza Reproductive Health Society, a Kenyan NGO that has been providing VMMC services since 2007 and EIMC since 2010. The participants did not receive any direct payment for participation but were provided with dinner after the discussion. Participation was voluntary and all participants provided verbal informed consent. Signed informed consent was not required since it would unnecessarily expose the participants to risk of loss of anonymity. An information document was provided to each participant explaining the risks and benefits of study participation and including contact information for the P.I. and the two IRBs. The study was approved by the Maseno University Ethics and Research Committee and the University of Illinois at Chicago Institutional Review Board.After providing consent, participants were asked to fill out a brief anonymous questionnaire to record their age, marital status, education, and cadre , number of male children, whether their son or sons were circumcised, and approximate number of procedures performed with each device. A discussion guide in English was developed based on the literature and our previous studies and covered the following topical areas: familiarity and experiences with EIMC devices, challenges using each device, advantages of each device, preferences for devices under different scenarios, and barriers and facilitators for scaling up EIMC. All participants had greater than a secondary school education and were fluent in English.The discussion, which lasted approximately two hours, was led by an experienced moderator, and a note taker was present to record the discussion nearly verbatim. In addition, the discussion was audio taped with the participants’ permission. The notes were typed within 48 hours and checked against the audio-tapes, with any discrepancies corrected. Transcripts were coded using Nvivo Version 8  with codes developed from the topics and probes targeted in the discussion guide. A few additional codes were developed from points that emerged after a preliminary reading of the transcripts.The study included 11 participants: 6 (55%) women and 5 (45%) men . The medParticipants were asked to name devices and techniques used for EIMC. In addition to the three devices that were the focus of the discussion, others that were mentioned were: the Gomco Clamp, Plastibel and Shang Ring. Of these, the Shang Ring has not been approved for EIMC. Free hand and dorsal slit surgical methods were also mentioned.Participants were asked their opinions and experiences with each of the devices and to describe the advantages and challenges of using each.The advantages to using the Mogen clamp that participants mentioned included that the procedure was fastest using the Mogen. Most participants agreed that it was very efficient at achieving hemostasis. As one participant said, “It never fails to deliver the pressure that is required to control bleeding.” Compared to the other devices, participants felt that adverse events, especially cases of bleeding, were fewer using the Mogen Clamp. Another advantage mentioned was that it is the easiest device to learn to use and the easiest to train providers to use.“There is a fear of the unknown when opening the device after cutting. There is anxiety to open up the clamp and check whether the glans has been severed. For smaller infants, as you pinch the foreskin to slide in the device, it is difficult to feel whether the glans is out of the way.”The biggest challenge in using the Mogen that all providers agreed upon was the risk of injuring or severing the glans penis. As one participant said, Several participants mentioned that the risk of a severed glans may be increased if the angle of the opening of the clamp is larger than it should be and that clamps should be checked regularly, since the opening can be enlarged by repeated autoclaving.The main advantage of using the AccuCirc device that participants cited was that there was no risk of injuring the glans. A typical statement was:Accucirc is 100% safe. There are no worries about severing the glans.”“The other advantage mentioned was that the AccuCirc comes in a complete sterile package with everything needed for the procedure. This was seen as ideal for use in situations where autoclaving and additional instruments may not be available. Participants considered this to be convenient and could be cost-saving.Nearly all participants cited the greatest disadvantage to using the AccuCirc as the risk of the device not achieving a complete cut of the foreskin. This is fairly easily addressed with scissors by simply completing the cut; however, some incomplete cuts result in bleeding, and participants were concerned that bleeding is an adverse event that occurs more often with the AccuCirc than the other devices.After inserting the ring you are not sure if there will be an incomplete cut or bleeding. Sometimes bleeding starts during the 1 hour post procedure observation period. One is not confident that they are sending a child home and he won’t bleed.”“It was pointed out that when the AccuCirc is used, there should be a clinician available who has experience in suturing. This is necessary in the event that the application of pressure to a bleeding wound does not staunch the bleeding. Someone mentioned that such suturing skills should be available no matter the technique used for EIMC, although they may be needed more when the AccuCirc device is used.Suturing skills should cut across [all the devices].”“The participants cited several advantages of using the PrePex device for EIMC. They felt that the cosmetic outcome was very good. They also felt that it was easy to learn to use and that it would be easy to train others. This is primarily because application of the PrePex device does not require suturing skills. However, all expressed concern that placement of the inner and outer rings was difficult and required a lot of practice. Some participants said that once the device is in place, mothers expressed fewer concerns than with other techniques; however, others said that with PrePex mothers called a lot with questions and concerns during the one-week period between placement and detachment of the device.A few participants pointed out that the PrePex had not been used previously for EIMC except in Rwanda and that there were aspects of its use that still required further refinement. One of these was the application of EMLA to achieve anesthesis. There was the question of how best to apply the EMLA. But of more concern to all the clinicians was that the EMLA did not achieve the level of anesthesis required for the comfort of the infant, and the levels of pain were very troubling.If you read the anatomy of innervation for the penis, you will see that EMLA only numbs the ventral side and the dorsal nerve is not touched.”“The biggest challenge I faced was pain, especially when removing adhesions. I would say EMLA doesn’t work.”“Lignocaine injection would be better because with PrePex, babies cry a lot in pain.”“It was the consensus that a dorsal block similar to that used with the other two techniques was as necessary when using the PrePex as when using the other devices.The participants spent quite a lot of time expressing their concerns about placing the inner ring of the PrePex device correctly so that it interfaces with the outer placement ring. Some were still experimenting with how to best achieve proper placement.During training we were told to insert the ring perpendicularly, but I found a different way where the ring approaches the glans horizontally. It requires practice so you get better with time.”“Some discussed the difficulties of placing the inner ring with different penile and foreskin sizes:If you get a short shaft and a long foreskin, placing the ring is quite hard.”“Another challenge is a narrow foreskin. Makes it hard to insert the ring and the skin might tear. With the narrow foreskin it is also difficult to view whether ring is in place so there is a fear of invagination.”“If the skin tears or you have a hard time placing the ring, you might have to resort to using a Mogen. We have had three such cases [out of a total of 50 cases].”“The participants were asked to weigh the challenges and advantages of each EIMC method and to express their preference under three different scenarios: First, if they themselves are performing the procedure; second, if a different provider is circumcising their infant; and third, if EIMC is scaled up in Kenya and throughout east Africa.Five of the 11 participants expressed their preference for the Mogen. The reasons they gave included the reduced chances of bleeding, reduced pain due to local anesthesia, and speed and ease of the procedure. One participant said,I believe the foreskin should be removed instantly, so [I prefer] the Mogen.”“Three participants expressed a preference for the PrePex, saying that the pain is brief and the cosmetic outcome is good. Two participants said that they would prefer the PrePex, but only if local anesthesia was administered. Two participants said their choice would depend on the age and size of the baby.It depends on age. Up to 30 days I would prefer AccuCirc. For greater than 30 days I would prefer Mogen.”“AccuCirc and PrePex, depending on what I see on the baby. If the baby is bigger and parent is ok with a non-surgical method, then I would use PrePex. Otherwise I would use AccucCirc because of safety.”“These participants were concerned that the risk of incomplete cuts and bleeding with the AccuCirc was greater with larger, older babies.One participant said that he had no preference; he was fine with using any of the three methods.Under these conditions, most of the participants expressed preference for the AccuCirc.Accucirc because there is 100% surety of not severing the glans. The circumcision cut is achieved instantly. There are no unknowns like odor with PrePex.”“Accucirc because of safety, and also because of my experience. My son was circumcised with Mogen and I was very worried about severing the glans.”“Accucirc because of safety of the glans.”“Two participants said that they would prefer the use of Mogen, but only if they knew and trusted the provider; otherwise they would opt for the AccuCirc:Mogen, if done by a trusted colleague. Accucirc if there is no trusted health care worker available because of safety.”“All my sons have had surgical circumcisions. I would go for Mogen if I trust the provider. If I was not a clinician, I would go for AccuCirc because any adverse events are manageable and don’t have far reaching consequences.”“Mogen, but I would ensure it is an experienced provider.”“Only one person preferred that her son be circumcised using the PrePex device.My son was circumcised with Mogen and he cried [for hours]. I would go for PrePex. Mums all say that the baby does not cry once the device is placed.”“The study participants were unanimous in their preference for AccuCirc as the device to be chosen in the event of a national scale-up of EIMC. The major reasons were due to its safety, ease of operation, and costs in terms of human resources needed.AccuCirc because in many health facilities there is a shortage of staff. It needs only one operator. PrePex may need two. Also safety reasons, since it is safer than Mogen. Also, logistics for sterilization in public facilities will be easier to manage with the AccuCirc kit, which comes complete”“If there is no follow up, Prepex device is locked out. I would go for Accucirc because it is cheaper in terms of human resources.”“AccuCirc because of workload. If babies are many, health care workers might be exhausted, and chances of severing glans are eliminated. AccuCirc is easier with smaller babies.”“Participants had many insights into possible barriers and ways in which some of them might be overcome. Their responses can be divided into three different areas: community factors, parental factors, and provider/facility factors.Regarding community factors, it was pointed out that EIMC is little known or understood in Kenya, among both communities where circumcision is traditionally practiced and where it is not traditionally practiced. The consensus was that it would take time for EIMC to be widely adopted by either type of community.Some communities want to circumcise later when it is considered a rite of passage. Non circumcising communities find it suspicious. ‘Why are they forcing us to do what our forefathers did not do?’ This brings about identity issues.”“The uncircumcised adults do not allow their infants to be circumcised. As more men get circumcised, EIMC may be more acceptable.”“The circumcised boy (for now) is the anomaly, not the norm.”“The current group of infants [who are getting circumcised], once they reach nursery, it will be more the norm.”“Regarding parental factors, the participants felt that concerns about pain and safety were especially salient for mothers.Perceived pain by the parents. Parents feel that babies are still too small and need to rest. There is the perception that the child is delicate and should not be subjected to such trauma.”“Another factor mentioned was whether the father or an older brother has been circumcised. Most mothers will not make the decision to circumcise their baby without the father’s approval. This makes recruitment and consenting more difficult than for adult VMMC, and it often places the decision in the hands of the father.Fathers who have not been circumcised will not agree to have their son circumcised.”“Maybe the firstborn child was not circumcised and [the] mother does not want the younger son to be circumcised before the older one.”“Certain religious and cultural practices were mentioned as barriers to adoption. For example, in rural communities, mothers are not permitted to observe the penis of their boy child until after their post-partum vaginal discharge (lochia) has ceased. This can be anywhere from ten days to two months after the birth, requiring someone else—a sister or other family member—to bring the baby for the procedure.Also, some churches do not allow babies to get out of the house until after 2 months.”“Another participant mentioned that accessibility and cost will be factors contributing to uptake, and he pointed out that some parents seek the service in private clinics where it is expensive. And another said that many parents want more information about EIMC.We need education and demand creation.”“Regarding provider and facility level factors that should be taken into consideration if Kenya is to scale up EIMC, all the participants expressed doubt that staff in health facilities would take on the additional burden of providing EIMC unless they received incentives. This is in part because the history of introducing new services in health facilities—especially HIV prevention, care and treatment services—has included either additional remuneration or additional staffing to cover the new service. Another method of introducing additional services has been through parallel programs not integrated with existing public health services and implemented by partner organizations that hire and pay their own staff and receive separate donor funding.The perception of providers is that there are donor funds that should trickle down to them which is a challenge scaling up VMMC, and it will be the same with EIMC.”“They view the program as a cash cow. They expect cash since they don’t do it routinely.”“We trained over 20 healthcare workers in facilities to do EIMC, but none are currently offering the service in the facilities.”“The participants discussed possible solutions to these challenges and felt that it would take strong leadership from the Ministry of Health to integrate EIMC with maternal, neonatal child health (MNCH) services. If there were no additional funds to pay staff for adding EIMC to their duties, then achieving significant numbers of infant circumcisions will be challenging. However, the MOH could make EIMC a mandatory, reportable service and require facilities to meet targets.To make EIMCs to be part of the reportable data to the MOH might push the staff to do more procedures.”“Some other comments that participants had regarding scaling up EIMC nationally included concerns about getting informed consent from parents.Some mothers are willing to give consent for the procedure, but most need to consult the father of the baby. This can make recruitment more complicated and time-consuming than for VMMC.”“There was concern about safety on several levels. If providers do not do large numbers of EIMCs in some facilities, their skills may not be maintained, and there could be more adverse events than seen so far in research settings. One participant suggested that this problem may be especially acute in rural settings since uptake will likely be lower in rural areas—just the areas farthest from back-up emergency facilities. Another mentioned that diagnoses of signs and symptoms that make adult men ineligible for VMMC are more difficult to detect in infants.We take a history early in life and may miss out on underlying congenital anomalies. With adults there is a clear history, making their screening easier.”“As policymakers and donors consider whether and how to transition to sustainable models of male circumcision for HIV prevention, some programs are assessing the feasibility and safety of introducing EIMC services into health facilities as part of MNCH programs –10. KnowThere was no one device that was seen to be clearly superior to the others. Each had its own advantages and disadvantages. Notably, provider preferences were situation-specific. Most preferred the Mogen if they themselves were performing the procedure. However, most were concerned that not everyone will have the skills necessary for optimal safety. When asked which device they would recommend if someone else were circumcising their son, most would opt for the AccuCirc because of the risk of severing the glans when using the Mogen. A minority preferred the PrePex, but only if the baby received local anesthesia, not EMLA cream (a eutectic mixture of lidocaine 2.5% and prilocaine 2.5%), as presently prescribed by the manufacturer. In the context of a national EIMC program, all participants agreed that AccuCirc would be the device they would recommend due to protection of the glans from laceration and to the provision of a pre-assembled sterile kit that overcomes the need for additional supplies or autoclaving. They also all agreed that scaling up EIMC, integrating it with existing MNCH services, will face many challenges, not least of which being to persuade providers to take on an additional workload when they are already overloaded and poorly compensated.“When I close that clamp, my heart is in my throat and I am praying that I have not pinched the glans.”WHO has pre-qualified three devices for EIMC: the Mogen, Gomco and Plastibell devices . The GomThe AccuCirc device avoids any risk of damage to the glans. It has undergone evaluation in a single-arm study in Botswana with no serious adverse events . A randoThe participants in our study expressed concern that integrating EIMC services with ongoing reproductive, maternal, newborn and child health platforms will be challenging primarily because of human resource constraints, competing priorities and desire for compensation for additional responsibilities. Such challenges have been voiced in the context of incipient programs in other countries  and in oThe primary limitation of this study is its small sample size of just 11 EIMC providers. As more doctors, clinical officers and nurses become trained and gain EIMC experience using different devices, the views regarding methods and how to scale up EIMC services safely and efficiently may change. This may be especially true once there is more experience with the PrePex device. However, at this time, we are unaware of any other study that has included providers who have experienced the use of the three main EIMC devices likely to be considered for scale-up of national EIMC programs in east and southern Africa. Thus this report should prove very useful to many programmers, donors and practitioners as they design their EIMC programs. Also, this study is novel for asking providers their opinions about which device is preferable under varying circumstances, going beyond preference for personal use to include preference for which device would be best in a national scale-up scenario.Based on the experience and preferences of the providers included in this study who have performed EIMCs using three different devices, the AccuCirc device may be the safest and most preferred device for use in a large-scale regional or national EIMC program. The process for bringing the AccuCirc device to the WHO pre-qualification stage should move forward as countries consider implementation of sustainable circumcision programs for comprehensive HIV prevention. In addition, this study highlights some of the many challenges that programmers will face as they seek to initiate EIMC in east and southern Africa. Among those mentioned in this study are: lack of familiarity with EIMC on the part of both populations and providers, cultural and religious barriers, demand creation, low initial uptake, obtaining parental consent, comprehensive screening of infants, safety of the procedure itself, emergency response capability, training of providers, ensuring maintenance of provider skills, and integration with maternal neonatal child health services.


Uterine arteriovenous malformation (AVM) can cause massive hemorrhage and is often treated with uterine artery embolization (UAE), which may lead to ovarian insufficiency. Thus, avoiding UAE should be considered, particularly in women undergoing fertility treatments. We present three women diagnosed with postmiscarriage AVM on color Doppler by transvaginal ultrasound imaging. They had no genital bleeding and a small mass, measuring 16–22 mm. If estradiol was >300 pg/mL when AVM was diagnosed, then a gonadotropin-releasing hormone agonist was administered. All three women underwent follow-up observation, revealing spontaneous mass disappearance. To avoid ovarian insufficiency risk with UAE, conservative management and close follow-up observation should be considered in patients with AVM without bleeding, particularly during the fertility treatment. Uterine arteriovenous malformation (AVM) is a rare condition, and although its precise incidence is unknown, most cases of AVM are undiagnosed. Thus, this condition may have a higher incidence than expected . AVM canAlternatively, some reports have described the spontaneous disappearance of AVM by expectant management , 11–15. Ethical Approval Statement. This study was conducted according to the guidelines of the Declaration of Helsinki and was approved by the Institutional Review Board of the University of the Ryukyus on 7 April 2015 (#936). All patients gave informed consent prior to her inclusion in the study.μg/day Suprecur®; Mochida Pharmaceutical Co., Ltd., Tokyo, Japan) was administered for 4 weeks. Furthermore, methylergometrine maleate was administered for 3 weeks to promote uterine contraction. Four weeks following diagnosis, the patient's estradiol level dropped to 5 pg/mL, the hCG level dropped to 4.9 mIU/mL, and the AVM disappeared  in the myometrium on ultrasonography 1 day after D&C. After 1 week, the abnormal vessels had grown to a size of 16 × 6 mm with abundant blood flow, which was shown on Doppler as a mosaic color pattern . No vagiPatient 3 had become pregnant by IVF-ET but had a missed abortion at 8 weeks of gestation, which ended in a complete abortion without D&C. Ultrasonography performed 1 week later revealed a cyst with a low-level echo (6 × 2 mm) and blood flow in the myometrium. Methylergometrine maleate was administered for 5 days. After 3 weeks, the cyst had grown to 20 × 15 mm with abundant blood flow . No vagiData regarding AVM following miscarriage are limited. Although the number of cases is small, we presented detailed cases of conservative management. Methylergometrine maleate was administered to all three cases to promote uterine contraction. A GnRH agonist was administered to cases 1 and 2 in whom estradiol levels were >300 pg/mL when AVM was diagnosed, which could have affected the growing AVM. In three patients with AVM without vaginal bleeding, the mass spontaneously disappeared without performing UAE. AVM does not always cause massive vaginal bleeding and spontaneously disappears in some patients. Therefore, for women concerned about ovarian insufficiency, particularly those undergoing fertility treatments, performing UAE should be carefully considered.Although AVM-induced massive vaginal hemorrhage is considered a rare disease, it is possible that the actual incidence is higher because of cases not being diagnosed . AsymptoBlood flow in the myometrium, verified by color Doppler on day 3 and at 6 weeks following normal delivery, has been reported . Of 93 cThere are many reports of UAE for uterine myoma –19. HoweWhen conservative treatment is selected for AVM, the use of methylergometrine maleate , 13 and In cases of AVM for which UAE is performed, early recurrence can develop with choriocarcinoma diagnosed after a subsequent hysterectomy . TherefoIn conclusion, to avoid ovarian insufficiency caused by UAE and potential complications in subsequent pregnancies, we believe that conservative management should be considered as the primary approach in hemodynamically stable patients, particularly in those undergoing fertility treatment.


Malnutrition in elderly patients is a common condition. Nevertheless, there is evidence on specific risk factors and problems of malnutrition in geriatric patients with neurological diseases. In this review, we summarize recent knowledge on malnutrition in different neurological diseases with a focus on elderly patients. This overview also provides strategies for a more specific and profound assessment of neurogeriatric patients to improve identification and treatment of malnutrition. Early and consequent treatment of malnutrition can lead to a decreased progression of the neurological disease and to a better quality of life in geriatric patients. An important and yet under-recognized geriatric syndrome is malnutrition. Although a widely accepted definition of malnutrition that adequately reflects its pathophysiology and its consequences is still lacking, the most relevant and recognized elements in the definition of malnutrition comprise the In clinical practice, the nutritional intake may be compromised in settings of: (1) pure chronic starvation without inflammation , (2) conditions with sustained mild inflammation , and (3) acute disease with significant inflammation which elevates resting energy expenditure   <20–22 is usually regarded as indicator for malnutrition in geriatric patients /22 cm  and calf-circumference below 31 cm are sensitive indicators of malnutrition and easily applicable , not affected by non-nutritional factors, and normalize through nutritional therapy  recommends three scores for screening malnutrition. The Malnutrition Universal Screening Tool (MUST) uses BMI, history of unexplained weight loss and acute illness effect  from 1619 participants of greater age, baseline weight, female gender, higher baseline disease severity assessed by Unified Parkinson Disease Rating Scale (UPDRS) scores, greater postural instability, difficulty in eating and drinking, lower cognitive scores, and baseline levodopa use (compared to dopamine agonists) were all associated with weight loss. Surprisingly difficulties such as swallowing, dyskinesia, depression, constipation, and nausea/vomiting were not significantly associated with weight loss in this cohort of early treated Parkinson's disease patients  patients with acute stroke are at a high risk for developing malnutrition. The National Institute for Health and Care Excellence (NICE) guideline states the necessity of screening and assessing all acute stroke patients for swallowing problems by appropriately trained staff before being given any oral food, fluid or medication  is higher in the elderly than in other adults. This is caused by an increased prevalence of epilepsy, neuropathic pain and behavioral disorders associated with dementia, for which AEDs are frequently administered. Extensive use of AEDs accounts for adverse drug reactions and contributes to the high frequency of untoward drug effects Lackner, . Since, Nutritional problems have also been found to be associated with multiple sclerosis (MS). Although it is reasonable to expect that due to the nature of MS  malnutrition is associated with MS, the prevalence of malnutrition in elderly MS patients is currently unknown , vascular dementia (25%), Lewy body dementia (15%), and frontotemporal dementia  have to be specifically addressed. The therapeutic goals in geriatric patients do not fundamentally differ from those for younger patients, but are weighted differently. While in younger patients the reduction of morbidity and mortality is of importance, the preservation of function, independence and quality of life are the focus in geriatric patients  felbamate, topiramate, zonisamide; (2) cardiovascular drugs ; (3) psychiatric drugs , and (4) non-steroidal anti-inflammatory agents (Landi et al., All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


One key advantage of VR is that sharing of virtual content can lead to more robust replication and representative sampling. A database of standardized content will help fulfill this vision. There are two objectives to this study. First, we seek to establish and allow public access to a database of immersive VR video clips that can act as a potential resource for studies on emotion induction using virtual reality. Second, given the large sample size of participants needed to get reliable valence and arousal ratings for our video, we were able to explore the possible links between the head movements of the observer and the emotions he or she feels while viewing immersive VR. To accomplish our goals, we sourced for and tested 73 immersive VR clips which participants rated on valence and arousal dimensions using self-assessment manikins. We also tracked participants' rotational head movements as they watched the clips, allowing us to correlate head movements and affect. Based on past research, we predicted relationships between the standard deviation of head yaw and valence and arousal ratings. Results showed that the stimuli varied reasonably well along the dimensions of valence and arousal, with a slight underrepresentation of clips that are of negative valence and highly arousing. The standard deviation of yaw positively correlated with valence, while a significant positive relationship was found between head pitch and arousal. The immersive VR clips tested are available online as  Blascovich et al.  proposedThe immersive video (or immersive VR clip) is one powerful and realistic aspect of VR. It shows a photorealistic video of a scene that updates based on head-orientation but is not otherwise interactive  between the ages of 18 and 24 took part in the study.YouTube, Vrideo, and Facebook. In total, more than 200 immersive VR clips were viewed and assessed. From this collection, 113 were shortlisted and subjected to further analysis. The experimenters evaluated the video clips and a subsequent round of selection was conducted based on the criteria employed by Gross and Levenson  head-mounted display (HMD). The Oculus Rift has a resolution of 2,160 × 1,200 pixels, a 110° field of view and a refresh rate of 90 Hz. The low-latency tracking technology determines the relative position of the viewer's head and adjusts his view of the immersive video accordingly. Participants interacted with on-screen prompts and rated the videos using an Oculus Rift remote. Vizard 5 software  was used to program the rating system. The software ran on a 3.6 GHz Intel i7 computer with an Nvidia GTX 1080 graphics card. The experimental setup is shown in Figure Participants viewed the immersive VR clips through an Oculus Rift HMD features a magnetometer, gyroscope, and accelerometer which combine to allow for tracking of rotational head movement. The data was digitally captured and comprised of the pitch, yaw, and roll of the head. These are standard terms for rotations around the respective axes, and are measured in degrees. Pitch refers to the movement of the head around the X-axis, similar to a nodding movement. Yaw represents the movement of the head around the Y-axis, similar to turning the head side-to-side to indicate “no.” Roll refers to moving the head around the Z-axis, similar to tilting the head from one shoulder to the other. These movements are presented in Figure The Oculus Rift remote control device that could scroll among options. Studies have shown that SAM ratings of valence and arousal are similar to those obtained from the verbal semantic differential scale  or arousal (low/high) were shown consecutively , ranging from a low of 1.57 to a high of 7.4. This compares favorably with arousal ratings on the IAPS, which range from 1.72 to 7.35 , with a low of 2.2 and a high of 7.7. This compares reasonably well with valence ratings on the IAPS, which range from 1.31 to 8.34.The immersive VR clips varied on arousal ratings  = 5.06, p = 0.03, r = 0.26, adjusted R2 = 0.05], although the direction was in contrast to our hypothesis. There was no significant relationship between standard deviation of head yaw with arousal . However, there was a significant relationship between average head pitch movement and arousal . Assumptions of the F-test for the significant relationships were met, with analyses showing homoscedasticity and normality of the residuals. The plots of the significant relationships are presented in Figures Pearson's product-moment correlations between observers' head movement data and their affective ratings are presented in Table F1, 1 = 5.06,Youtube which have a strict policy on the types of content that can be uploaded. Hence, it is not surprising that stimuli of negative valence and arousal were not captured in our selection of immersive videos. Regardless, the collection of video clips (which can be found here) should serve as a good launching pad for researchers interested to examine the links between VR and emotion.The first objective of the study was to establish and introduce a database of immersive video clips that can serve as a resource for emotion induction research through VR. We sourced and tested a total of 73 video clips. Results showed that the stimuli varied reasonably well along the dimensions of valence and arousal. However, there appears to be a lack of representation for videos that are of negative valence yet highly arousing. In the IAPS and IADS, stimuli that belong to this quadrant tend to represent themes that are gory or violent, such as a victim of an attack that has his face mutilated, or a woman being held hostage with a knife to her throat. The majority of our videos are in the public domain and readily viewable on popular websites such as Although not a key factor of interest for this paper, we observed variance in the length of the video clips which was confounded with video content. Long video clips in our database tend to be of serious journalism content  and naturally evoke negative valence. Length is a distinct factor of videos in contrast to photographs which are the standard emotional stimuli of photographs. Hence, while we experienced difficulty sourcing for long video clips that are of positive valence, future studies should examine the influence of video clip length on affective ratings.The second objective sought to explore the relationship between observers' head movements and their emotions. We demonstrated a significant relationship between the amount of head yaw and valence ratings, which suggests that individuals who displayed greater movement of side-to-side head movement gave higher ratings of pleasure. However, the positive relationship shown here is in contrast to that presented by Won et al.  who showR2 = 0.05). While we tried our best to balance efficient data collection and managing participant fatigue, some participants may not be used to watching VR clips at length and may have felt uncomfortable or distressed without overtly expressing it. This may have influenced their ratings for VR clips toward the end of their study session, and may explain the small effect size. Future studies can explore when participant fatigue is likely to take place and adjust the viewing duration accordingly to minimize the impact on participant ratings.One thing of note is the small effect sizes shown in our study . This can exist through allowing participants to sit, stand or walk freely, or even program depth field elements into the immersive videos and seeing how participants' rotational and translational head movements correlate with their affect. Exploring the effects of the added degrees of freedom will contribute to a deeper understanding on the connection between head movements and emotions.This study was carried out in accordance with the recommendations of the Human Research Protection Program, Stanford University Administrative Panel on Human Subjects in Non-Medical Research with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Stanford University Administrative Panel on Human Subjects in Non-Medical Research.The authors worked as a team and made contributions throughout. BL and JB conceptualized and conducted the study. AP contributed in the sourcing and shortlisting of immersive VR clips and in revising the manuscript. WG and LW acted as domain consultants for the subject and contributed in writing and revisions.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The cutoff value of the luminance ratio was 1.62, resulting in 66 FVL-positive and 13 FVL-negative specimens. The luminance ratio was significantly higher in the epithelial dysplasia-positive than -negative group (P<0.000 1). The objective AVM showed much higher consistency between histopathological results than did the two methods (kappa statistic=0.656). In conclusion, objective autofluorescence visualization has a potential as an auxiliary method for diagnosis of epithelial dysplasia.The autofluorescence visualization method (AVM) uses blue excitation light to assist in the diagnosis of epithelial dysplasia. It detects epithelial dysplasia as a black area, which is known as fluorescence visualization loss (FVL). In this study, we evaluated the detection accuracy for epithelial dysplasia of the tongue using the objective AVM and assessed its possible clinical utility. Seventy-nine tongue specimens clinically suspected to have leukoplakia or squamous cell carcinoma (SCC) were analyzed. First, the AVM was subjectively performed using the Visually Enhanced Lesion scope (VELscope), and the iodine-staining method was then performed. After biopsy, the histopathological results and the luminance ratio between the lesion and healthy tissue were compared, and a receiver operating characteristic curve was created. The cutoff value for the objective AVM was determined; the lesion was considered FVL-positive or -negative when the luminance ratio was higher or lower than the cutoff value, respectively. The histopathological diagnoses among the 79 specimens were SCC ( The iodine-staining method (IOM) has been used to detect oral SCC and epithelial dysplasia.7 In the IOM, healthy oral mucosa turns to a yellowish brown color secondary to the iodine-glycogen reaction; however, epithelial dysplasia of the oral mucosa, which has less glycogen, is visually detected as an iodine-unstained area because of the absence of this reaction. Although the IOM is a useful modality with which to detect epithelial dysplasia, it has several weak points: iodine is irritative to the mucosa, it is contraindicated in patients with allergy to iodine,7 and it cannot be used in keratinized mucosa, such as the gingiva and hard palate, because of the mechanism of iodine staining.1Epithelial dysplasia is often observed in the tissue surrounding oral squamous cell carcinoma (SCC),8 The AVM utilizes blue excitation light to detect the difference in luminance between healthy tissue and epithelial dysplasia. No drugs or other agents are required.12 Recently, several optical imaging system have been produced such as Visually Enhanced Lesion scope , EVINC , and Identifi 3000 , using different wavelength of light sources.14The autofluorescence visualization method (AVM) is another modality that has a potential for detecting epithelial dysplasia without the above-mentioned weak points of the IOM.16 Green light with a wavelength of 515 nm is then emitted from endogenous autofluorescence substances in healthy area.18 However, the collagen cross-links and basal lamina of tissue affected by SCC with epithelial dysplasia are destroyed,20 and glucose is highly consumed in malignant tissue even when in an aerobic environment (Warburg effect).21 The concentration of flavin adenine dinucleotide, which is the main source of cellular fluorescence, then decreases in the epithelial dysplasia.24 Therefore, the lower level of endogenous autofluorescence substances in tissue affected by epithelial dysplasia and SCC of the oral mucosa has no fluorescence energy, resulting in the appearance of a black area detected as fluorescence visualization loss (FVL)  emitted from the VELscope contacts these endogenous autofluorescence substances, the level of fluorescence energy emitted from the endogenous autofluorescence substances will become lower than that of the light energy emitted from the VELscope.ss (FVL) .27 The sensitivity and specificity of EVINCE also resulted in this range, however, the result showed significant variation between unskilled examiner and adept examiner.14 Therefore, to elucidate these variability possibly based on surgeon’s skill or wonder for judgment, we tried to quantify the luminance of FVL and normal tissue  by image processing software as the objective AVM in this study. We also evaluated the possible clinical indications for the objective AVM in comparison with the subjective AVM and the conventional IOM.In previous studies, the AVM had been performed to detect FVL by visual inspection (subjective AVM) resulting in relatively large variability in the diagnostic accuracy; for example, sensitivity varied from 30.0% to 100.0%, and specificity varied from 15.3% to 80.8%.We examined 79 specimens obtained from 62 patients  with an average age of 59.6 years  who were referred to our department and underwent biopsy under a clinical diagnosis of leukoplakia or SCC of the tongue from February 2014 to November 2016 . This stThe first step of the procedure was a conventional oral examination including palpation. The subjective AVM was carried out for the area visually suspected to be affected by epithelial dysplasia and the presence of FVL was illuminally detected subjectively. Next, a photograph was taken for the subjective AVM. Then, the iodine-unstained area was detected by the IOM. These procedures were performed by two specialists in oral and maxillofacial surgery who had 19 and 27 years of clinical experience in oral cancer treatment. The luminance ratio between the lesion and healthy tissue was then calculated using image-analysis-software. Consequently, biopsy was performed and the result of the histopathological analysis was compared with the luminance ratio, and the cutoff value for the objective AVM was determined. Then, the objective AVM was assessed on the basis of this semi-quantitative value. The detection accuracy of each modality  was also analyzed.F-value was 8.0. Photos at visual inspection and the IOM were taken with a flash in a room with white light, and those for the AVM were taken without a flash and with the room light turned off.All photographs of lesion sites were taken by single-lens reflex camera  equipped with an 18- to 55-mm macro lens (Canon) and macro ring light . The photographing conditions were as follows: the ISO film speed was AUTO, shutter speed was 1/125 s, and The subjective AVM was performed using a VELscope and VELscope camera attachment kit . The distance between the emission site of the VELscope and lesion site was set to 15 cm, and photographs were taken under blue excitation light. The green light area was defined as healthy mucosa area, and the black area of FVL was defined as lesion area.First, the target lesion on the tongue was washed with physiological saline solution and air-dried, and 1.5% diluted iodine was then applied. After 3 min, the area was fully rinsed and all surplus iodine liquid was removed. Consequently, the areas stained and unstained by iodine were confirmed. The stained area was defined as the epithelial dysplasia-negative area, and the unstained area was defined as the epithelial dysplasia-positive area.For biopsy, the lesion was resected including both the blackest point identified by the subjective AVM and the iodine-unstained area. In cases without an iodine-unstained area, only the blackest point was included in the biopsy specimen. Conversely, in cases without the blackest point, only iodine-unstained area was included in the biopsy specimen. In cases with neither a blackest point identified by the AVM nor an iodine-unstained area, the area macroscopically suspected to be the lesion was resected as the biopsy specimen.28  was defined as the epithelial dysplasia-positive group, and that of leukoplakia without dysplasia (Lw/oD) was defined as the epithelial dysplasia-negative group. The criteria of histopathological diagnosis of epithelial dysplasia were in accordance with WHO criteria28 .The photographs of the subjective AVM images viewed from the VELscope were analyzed by Image J software , and the luminance ratio was calculated. First, all photographs were converted from color images to grayscale, and the luminance level was measured by a precise circle with a 12-pixel diameter. The blackest point of FVL area was defined as the luminance level of the lesion, and the average luminance level of three points in the white area of the same image, which was originally green light area, was defined as the luminance level of the healthy area. The LNR was then determined using the following formula: LNR=luminance of the healthy area/luminance of the lesion.http://www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmedEN.html, accessed 28 October 2015).29 The maximal point of addition of the sensitivity and specificity on the ROC curve was defined as the cutoff LNR value according to the Youden index,30 which is the criterion of determination of the existence of FVL  curve was created by EZR statistics software , and the Mann–Whitney The subjective AVM showed 66 (83.5%) FVL-positive and 13 (16.5%) -negative specimens. On the other hand, the conventional IOM showed 74 (93.7%) iodine-unstained areas and 5 (6.3%) iodine-stained areas .Patient No. 12 was one of the typical type of patients for whom the subjective AVM and the conventional IOM could detected the epithelial dysplasia lesion well. There was lace-like white plaque at the lateral edge of the tongue, which was macroscopically suspected to be epithelial dysplasia. With VELscope emission light, the area of suspected epithelial dysplasia was detected as black area (FVL) and surrounding healthy area turned bright white. The lesion was also detected as iodine-unstained area by the conventional IOM. Histopathologically, hematoxylin and eosin staining of the lesion showed destruction of the basement membrane and tumor cell invasion into the submucosal tissue with keratin pearl formation, resulting the diagnosis of oral SCC .in situ in 30 specimens, LwD in 34 specimens, and Lw/oD in 15 specimens. Therefore, 64 specimens were epithelial dysplasia-positive, and 15 were epithelial dysplasia-negative. Among the 64 histopathological epithelial dysplasia-positive specimens, the number of FVL-positive or -negative specimen was 55 or 9 in the subjective AVM, and that of iodine -unstained or -stained specimen was 61 or 3, respectively . Based on the combinatorial results of the LNR and pathological diagnosis, an ROC curve was created. The area under the ROC curve was 0.84, which was moderately accurate, and the 95% confidence interval (CI) was 0.69–0.98. On the created ROC curve, the maximal point of addition of sensitivity and specificity was 1.620, which was defined as the cutoff value for the criterion of judgment of epithelial dysplasia for the objective FVL area . Thus, tP<0.000 1)  and that in the epithelial dysplasia-negative group was 1.68 . The LNR in the epithelial dysplasia-positive group was significantly higher than that in the epithelial dysplasia-negative group (0.000 1) .We also analyzed the correlation of the objective AVM and the conventional IOM by combining the result of the two methods. This analysis showed that 58 specimens (73.4%) were objectively FVL-positive and iodine-unstained, 3 specimens (3.8%) were FVL-positive without an iodine-unstained area, 16 specimens (20.3%) were FVL-negative and iodine-unstained, and 2 specimens (2.5%) were FVL-negative without an iodine-unstained area. All specimens with both objectively FVL-positive and iodine-unstained lesions were histopathologically diagnosed as epithelial dysplasia-positive.The 12 of 15 (80.0%) specimens histopathologically diagnosed as epithelial dysplasia-negative were FVL-negative; however, 13 of these 15 (86.7%) specimens showed an iodine-unstained area, and only 2 (13.3%) showed an iodine-stained area .The detection accuracy of the subjective AVM, the IOM and the objective AVM for the diagnosis of epithelial dysplasia of the tongue was as follows: sensitivity; 85.9%, 95.3%, and 90.6% specificity, 26.7%, 13.3%, and 80.0% positive predictive value, 83.3%, 82.4%, and 95.1% negative predictive value, 30.8%, 40.0% and 66.7% accuracy, 74.7%, 79.7%, and 88.6% positive likelihood ratio, 1.17, 1.10, and infinity; and negative likelihood ratio, 0.53, 0.35, and 0.12, respectively. The degree of confidence between the histopathological diagnosis and the results of these auxiliary diagnostic modalities were as follows; the subjective AVM was fair with a kappa value of 0.132 , IOM was slight with a kappa value of 0.116  and the objective AVM was substantial with a kappa value of 0.656  .Six specimens were assessed as false-negative by the objective AVM. Histopathologically, two were assessed as SCC and four were assessed as LwD. Specimen No. 2 was typical type of false-negative by the objective AVM. There was macroscopically suspected lesion area with iodine-unstained area, however, the FVL was not apparent, and the histopathological diagnosis was SCC . On the In this study, we tried to quantify the luminance of FVL for the objective AVM and calculated a cutoff value of 1.62. This is the first attempt to provide an AVM device capable of objectively evaluating the viewing function of an eye to be examined. The present study thus contains significant meaning for the diagnosis and treatment of oral cancer including epithelial dysplasia.31 and a statistically significant difference has been found in the malignant transformation rate of patients with leukoplakia with epithelial dysplasia vs leukoplakia without epithelial dysplasia.32 Although leukoplakia with moderate or severe dysplasia would be selectively and immediately excised after biopsy, while that with mild dysplasia would not be so hastly treated, there is still a significant difference in the transformation rate of malignancy. However, there are opposite opinions regarding the relationship between malignant transformation and epithelial dysplasia.34 Because the statistically significant reported risk factors for malignant transformation of leukoplakia include the presence of epithelial dysplasia,35 we support the opinion that surgical resection with an adequate safety margin including the area of epithelial dysplasia would be effective in preventing malignant transformation.Epithelial dysplasia has been reported to transform to oral SCC,The number of patient in this study might have been relatively low, and the number of pre-malignant and malignant specimens was higher than that of leukoplakia without dysplasia specimens. There are two plausible reasons. One is that the patients who were subjectively diagnosed as non-malignancy were emitted before examination by the two specialists. These patients had been diagnosed as lichen planus, pemphigus, and papilloma; they also received treatment and were undergoing careful follow-up at the time of this writing. The other plausible reason is that our hospital is one of two university-hospitals in Kanagawa prefecture that have an oral and maxillofacial surgery department; thus, our patients tend to have more severe diagnoses than patients in the oral and maxillofacial surgery departments of our general branch hospitals.In the present study, the objective AVM showed higher specificity, positive predictive value, negative predictive value and accuracy than did the subjective AVM and the conventional IOM. In particular, high positive and negative predictive values can provide facilitate decision-making regarding the adequate safety margin at biopsy or excision surgery. In addition, the degree of confidence between the histopathological diagnosis and the objective AVM was higher than that of the other two modalities, indicating optimistic potential for this technique as auxiliary methods for diagnosis of epithelial dysplasia.However, there are several concerns regarding the objective AVM; one is the slightly higher false-negative ratio compared with the conventional IOM. The correlation between the objective AVM and the conventional IOM was relatively high in epithelial dysplasia-positive patients, which suggests that both methods have a certain level of reliability. The most plausible reason for the slightly higher false-negative diagnosis of the objective AVM could be related to the location of the lesion and the healthy area. All false-negative lesions detected by the objective AVM were on the lateral edge of the tongue, and the healthy area was on the dorsum of the tongue.27 Therefore, the setting of the AVM has to be reconsidered when the healthy area is located only on the dorsum of the tongue. Another plausible reason for the slightly higher false-negative diagnosis associated with the objective AVM is that the protocol of the objective AVM involves many steps to achieve a diagnosis, and a complicated calculation is required to determine the LNR and perform analysis using Image J software.The lesion showed relatively low FVL and the healthy area on the dorsome of tongue showed a relatively low level of green fluorescence, which led to a decreased luminance ratio between the lesion and healthy areas resulting a false-negative diagnosis . This hy36Interestingly, the false-negative patients of the objective AVM and the conventional IOM were totally different. The reason for this could be the difference in the mechanism to detect epithelial dysplasia. Moreover, we consider that the genetic alteration in each specimen might have differed, leading to the different level of FVL and patterns of false-negative results among the methods. Further investigation is necessary to evaluate the relationship between the false-negative pattern and the expression level of the reported molecular changes associated with dysplasia or transformation to oral SCC.In this study, only tongue lesions were analyzed to compare the objective AVM with the other two methods because adequate number of patients has not yet been analyzed. One of the advantages of both AVM techniques is that they are indicated for evaluation of keratinized mucosa, such as the gingiva and hard palate. We hypothesize that the cutoff value of each anatomic sites may be different, however, we do not yet know how these factors are related to endogenous fluorescence substances or what kind of genetic alteration which relates to the level of endogenous fluorescence substances will be found in epithelial dysplasia area and affect LNR. Therefore, further investigation for other sites of the oral cavity and reconsideration of the setting of the objective AVM would be required.At this moment, chair-side evaluation by the objective AVM is available and the cutoff value for tongue lesion was decided in this report. For future feasibility of the objective AVM, cutoff value for another site of lesion in the oral cavity will be required at least. Then, software developing that minimize the time consumption will also be required.et al.13 had just reported a new attempt of objective methods of EVINCE by calculating ROC curve, area under the curve, and regions of interest, whose methods were similar to ours and their concept was probably based on same intensions to ours. Having said that, there are three different points from our study in addition to difference of devices as follows; (1) our study proposed comparison of three modalities (the subjective and objective AVM of VELscope and IOM); (2) our study also proposed comparison of LNR between different histopathological diagnosis; and (3) the first step of examination was performed just before biopsy, which is not chair-side usage of the device. Considering these two manuscripts, building objective and reliable methods for optical imaging system would be one of the next subjects to develop visual inspection devices.Coincidently, Yan When the objective AVM will be used in practice, it will be indicated not only for decision of biopsy or excision, but also observation after surgical treatment and screening for oral epithelial dysplasia at general clinics.In conclusion, the objective AVM is suggested to have optimistic potential as a clinical auxiliary method comparable with the conventional IOM, but still may miss overt carcinomas.


Stand-alone text message–based interventions can reduce binge drinking episodes (≥4 drinks for women and ≥5 drinks for men) among nontreatment-seeking young adults, but may not be optimized. Adaptive text message support could enhance effectiveness by assisting context-specific goal setting and striving, but it remains unknown how to best integrate it into text message interventions.The objective of this study was to evaluate young adults’ engagement with a text message intervention, Texting to Reduce Alcohol Consumption 2 (TRAC2), which focuses on reducing weekend alcohol consumption. TRAC2 incorporated preweekend drinking-limit goal-commitment ecological momentary assessments (EMA) tailored to past 2-week alcohol consumption, intraweekend goal reminders, self-efficacy EMA with support tailored to goal confidence, and maximum weekend alcohol consumption EMA with drinking limit goal feedback.We enrolled 38 nontreatment-seeking young adults (aged 18 to 25 years) who screened positive for hazardous drinking in an urban emergency department. Following a 2-week text message assessment-only run-in, subjects were given the opportunity to enroll in 4-week intervention blocks. We examined patterns of EMA responses and voluntary re-enrollment. We then examined how goal commitment and goal self-efficacy related to event-level alcohol consumption. Finally, we examined the association of length of TRAC2 exposure with alcohol-related outcomes from baseline to 3-month follow-up.Among a diverse sample of young adults , response rates to EMA queries were, on average, 82% for the first 4-week intervention block, 75% for the second 4-week block, and 73% for the third 4-week block. In the first 4 weeks of the intervention, drinking limit goal commitment was made 68/71 times it was prompted (96%). The percentage of subjects being prompted to commit to a drinking limit goal above the binge threshold was 52% (15/29) in week 1 and decreased to 0% (0/15) by week 4. Subjects met their goal 130/146 of the times a goal was committed to (89.0%). There were lower rates of goal success when subjects reported lower confidence (score <4) in meeting the goal (76% [32/42 weekends]) compared with that when subjects reported high confidence . There were reductions in alcohol consumption from baseline to 3 months, but reductions were not different by length of intervention exposure.Preliminary evidence suggests that nontreatment-seeking young adults will engage with a text message intervention incorporating self-regulation support features, resulting in high rates of weekend drinking limit goal commitment and goal success. Young adults have the highest prevalence of hazardous alcohol consumption among all age groups , largelyOne design feature potentially limiting TRAC1’s effectiveness was that drinking limit goal support was not optimized. In examining EMA data collected from those exposed to TRAC1, we found that subjects declined to commit to a weekend drinking limit goal based on the binge threshold roughly 40% of the times they were prompted and that goals were met only 65% of the time . In examTo improve context-specific goal support, we incorporated drinking limit goal commitment EMA tailored to past 2-week alcohol consumption, intraweekend goal reminders, self-efficacy EMA with support tailored to goal confidence, and maximum weekend alcohol consumption EMA with drinking limit goal feedback into the TRAC intervention .Our primary aim was to evaluate young adult engagement with the TRAC2 goal support features. Specifically, we examined responses to goal commitment and goal self-efficacy EMA, and how responses related to event-level alcohol consumption. We hypothesized that the percentage of responses indicating a willingness to commit to a weekend drinking limit goal tailored to past drinking  would be higher compared with the 60% willing to commit to the fixed binge threshold used in TRAC1. Our secondary aim was to examine the association of length of TRAC2 exposure with alcohol-related outcomes from baseline to 3-month follow-up, including maximum drinks per drinking occasion on weekends, prevalence of reporting a binge drinking episode on a typical drinking week, and alcohol-related consequences. We hypothesized that subjects who used the TRAC2 intervention for longer periods would have greater reductions in alcohol-related outcomes than those who used it for shorter periods.From April 1 to June 9, 2016, a convenience sample of 143 patients aged 18 to 25 years who presented to an urban emergency department (ED) were identified through medical record review. Following introduction by a member of the care team, 117 young adults who were medically stable and not seeking treatment for substance use disorder were approached by research staff and 72 (66.7%) of them provided consent to complete a questionnaire, including assessments of alcohol use severity. Young adults reporting recent hazardous alcohol consumption based on an Alcohol Use Disorder Identification Test for Consumption (AUDIT-C) score of ≥3 for women or ≥4 for men .” If subjects completed at least 50% of EMA during the 2-week run-in, they were offered the option of enrolling in the TRAC2 intervention by texting “Go.” We included the run-in period to exclude those individuals who expressed initial willingness in participation but did not exhibit adequate engagement through texting.Subjects who met the run-in eligibility criteria and opted in (n=38) were sent EMA each Thursday, Friday, Saturday, and Sunday. On Thursdays, subjects were queried about their weekend drinking plans and willingness to commit to a drinking limit goal. Instead of asking individuals to commit to a weekend drinking limit goal based on the binge threshold (as done in TRAC1), we used an algorithm that prompted a drinking limit goal based on the running average of the largest number of drinks consumed by that individual on any occasion in the prior 2 weekends. When the average number of drinks in prior 2 weeks was greater than 10, the drinking limit goal was set at 10. When the average number of drinks in prior 2 weeks (#) was reported as less than or equal to 10 but greater than binge (>4/5 drinks), their drinking limit goal was (#) minus 1. This adaptive goal prompt feature fits with harm reduction principles .To increase goal salience proximal to contexts of high cue reactivity and peer pressures , we sentIn addition to these goal support features, we chose to provide individuals more control over how long they use the TRAC2 intervention using enhanced active choice , where aAll subjects, including those enrolled in the ED but not exposed to TRAC2, were asked to complete a follow-up Web-based survey 3 months after baseline assessments and were compensated US $40 upon completion. Subjects were notified by SMS to access the survey website and those who did not complete their Web-based follow-up within 1 week were contacted once through email as a reminder.At baseline, subjects reported their age, sex, race, ethnicity, and education (college enrolled: yes/no).During screening, we asked subjects the AUDIT-C and the question: “How many days have you had ≥4 (for women) or ≥5 (for men) standard alcoholic drinks in the past month?” At baseline and at 3-month follow-up, subjects were presented with a calendar and a visual reference displaying standard drink amounts and were asked to report their alcohol consumption by day of the week for both a typical and heavy drinking week (Daily Drinking Questionnaire ). We useAt baseline, subjects were asked to report frequency of other drug use over the past 3 months using the NIDA Modified Alcohol, Smoking, and Substance Involvement Screening Test (NM-ASSIST ). Cigare” reported as a continuous variable. We used this value to calculate whether they met their drinking limit goal (when made), coded as did not meet goal=0 and met goal=1.Drinking intentions were measured each Thursday through responses to: “Do you plan on drinking this weekend?” coded as no=0 and yes=1. Willingness to commit to a drinking limit goal was measured through responses to: “Would you be willing to commit to a goal to drink less than [X] drinks on any occasion this weekend?” coded as no=0; and yes=1. Drinking limit goal self-efficacy was measured through responses to: “How confident are you that you will meet this goal on a scale from 1  to 5 (completely)?” For the purposes of this study, we used the lowest value reported over the weekend as a measure of self-efficacy vulnerability. Finally, we measured the maximum number of drinks consumed each weekend through responses to: “Between Thursday and today, what is the MOST drinks you had on any occasion? We first examined baseline characteristics of enrolled subjects, identifying any differences across groups of different durations of TRAC2 engagement (number of 4-week blocks enrolled) using analysis for variance for mean comparisons, Kruskal-Wallis test for medians, and chi-square test for categories. We then calculated EMA response rates across weeks by group. To understand changes in alcohol consumption over weekends, we visually inspected distribution of maximum drinks consumed on any weekend day across groups and modeled data by group using repeated-measures linear regressions. We first declared data as a panel to account for clustering within individuals. We specified “max drinks” as a count variable with a Poisson distribution and modeled random effects, given the variability in maximum drinks consumed by subjects in week 1 (intercept). We specified that residuals were autoregressive. To understand predictors and processes influencing goal success, we used chi-square tests to examine univariate associations between selected correlates of drinking behavior and drinking goals being met. Finally, we tested the significance of differences between baseline and 3-month follow-up reports using Wilcoxon signed-rank tests (for maximum drinks and negative consequences) and 2-sample test of proportions . All statistical tests were conducted using Stata 14.0 .A total of 50 subjects were enrolled in the ED. Baseline descriptive statistics are reported in P=.01) and lower percentage of college-enrolled subjects . The percentage of subjects who continued to enroll in TRAC2 was 76% (29/38) after the first 4-week block, 50%(19/38) after the second 4-week block, 24% (9/38) after the third 4-week block, 16% (6/38) after the fourth 4-week block, 5% (2/38) after the fifth 4-week block, and 2% (1/38) after the sixth 4-week block. The only significant differences in baseline characteristics between subjects based on length of TRAC2 enrollment were higher prevalence of cannabis use among subjects enrolled for 4 weeks and higher prevalence of opioid use among those enrolled for 12 weeks. Stage of change was not associated with length of voluntary TRAC2 enrollment  completed the run-in successfully and enrolled in TRAC2. Comparing those who were excluded during the run-in with those who successfully enrolled in the intervention period, there was a higher percentage of Hispanic subjects  of subjects reported a plan to drink over the weekend, which decreased to 46% (15/33) by week 4. Among subjects who reported a plan to drink over a given weekend in the first 4 weeks of the intervention, on average reported being willing to commit to the proposed drinking limit goal 96% (68/71) of weekends. The percentage of subjects being prompted to commit to a drinking limit goal above the binge threshold was 52% (15/29) in week 1 and decreased to 0% (0/15) by week 4. The percentage of weekend days where subjects reported high confidence (score 4 or 5) in meeting their drinking limit goals on both Friday and Saturday in the first 4 weeks of the intervention was, on average, 60% (68/71 weekends), with no changes in confidence across time.The median number of maximum drinks consumed on any weekend day by length of TRAC2 enrollment and regression model output is shown in P=.01). There were lower rates of meeting drinking limit goals when the goal prompt was greater than binge levels (77% [26/34 weekends]) than when the goal was at the binge threshold . Finally, there were lower rates of goal success when subjects reported lower confidence (score <4) in meeting the goal on either Friday or Saturday (76% [32/42 weekends]) compared with that when subjects reported high confidence .The percentage of weekends where the drinking limit goal was met was, on average, 89.0% (130/146 weekends), with no significant change over time. When examining factors associated with goal success, we found that goal success rates were higher among black subjects (98% [51/52 weekends]) than white subjects  completed Web-based follow-up surveys at 3 months. No baseline factors including sex, college education, race, baseline alcohol use severity (AUDIT-C score), or stage of change were associated with attrition. There were trends indicating reductions in maximum drinks consumed over typical weekends and prevalence of binge drinking in all groups exposed to TRAC2. There were significant reductions in the number of alcohol-related consequences among TRAC2-exposed participants see .In this study, we found high levels of engagement with a text message intervention incorporating adaptive goal support features among a racially diverse sample of nontreatment-seeking young adults at varying stages of change. Among subjects who met run-in criteria, there were high response rates to EMA during TRAC2 exposure. Consistent with our a priori hypothesis, we found that there was a high willingness to commit to adaptive drinking limit goals (96% of time), which is higher than the 40% goal commitment willingness when we used a fixed “binge” threshold with a similar cohort of young adults in TRAC1 . This suRegarding the safety of prompting individuals to commit to goals to limit drinks at levels found to be associated with negative outcomes, we found that it was a time-limited issue. Despite more than half of subjects being prompted in week 1 to commit to a drinking limit goal above a binge threshold, by week 4 no subject was being prompted to limit drinks above binge threshold. We also recognize that the binge threshold is a somewhat arbitrary cutoff and that there is a linear relationship with escalating blood alcohol content and consequences , thus suTo our knowledge, this is the first published report of an alcohol intervention that incorporates an algorithm that gradually steps an individual down gradually over time. We focused on goal support, given the importance of goals in behavior change generally  and for We found that 76% (29/38) of enrolled subjects chose to continue the TRAC2 program after the first 4 weeks. We were surprised that a third of subjects chose to continue the program after 12 weeks, with 1 individual continuing the program up to 28 weeks. These findings suggest that most individuals exposed to TRAC2 find it valuable. It also highlights the importance of choice architecture in behavioral intervention designs and supports “enhanced active choice”  where usThis was a pilot study with a small number of participants. As such, differences may exist that we were not powered to detect. Subjects were sampled from an urban ED and therefore may not represent young adults broadly. All outcome data were self-reported and subject to possible bias. A quarter of young adults who expressed interest in study participation in the ED did not complete at least half of EMA sent over the first 2 weeks and were thus excluded from receiving the TRAC intervention. This may indicate that not all young adults with hazardous alcohol use are willing or interested in interacting through digital modalities such as SMS to improve health behaviors. We did not use randomization procedures, given the primary aim of determining acceptability, and therefore, cohorts may differ in both measured and unmeasured ways. Finally, the response rates to goal self-efficacy EMA were significantly lower than other EMAs. This may have been due to the fact that either the timing of the messages was not optimal  or the nature of the query was unacceptable.Preliminary evidence suggests that, among a diverse sample of nontreatment-seeking young adults with past hazardous alcohol consumption, adaptive goal support text message intervention features are acceptable and potentially effective in supporting short-term reductions in alcohol consumption. Future research is needed to replicate findings in a larger cohort and determine which features of adaptive goal support optimize behavioral change.


There is an increasing trend in association football (soccer) to assist referees in their decision-making with video technology. For decisions such as whether a goal has been scored or which player actually committed a foul, video technology can provide more objective information and be valuable to increase decisional accuracy. It is unclear, however, to what extent video replays can aid referee decisions in the case of foul-play situations in which the decision is typically more ambiguous. In this study, we specifically evaluated the impact of slow-motion replays on decision-making by referees. To this end, elite referees of five different countries (n = 88) evaluated 60 different foul-play situations taken from international matches, replayed in either real time or slow motion. Our results revealed that referees penalized situations more severely in slow motion compared to real time (e.g. red card with a yellow card reference decision). Our results provide initial evidence that video replay speed can have an important impact on the disciplinary decision given by the referee in case of foul play. The study also provides a real-life test-case for theories and insights regarding causality perception. In sporting events, high-speed cameras are frequently used to provide slow-motion replays of important game situations in every detail. Fans and sport commentators have immediate access to this footage and they increasingly rely on it to scrutinize referee decisions. Furthermore, the International Football Association Board agreed to introduce experiments with video assistant referees who can rely on video clips in slow motion and/or real time to evaluate and review referee decisions on the spot. Although referees on the field of play have to decide in real time, these slow-motion replays are frequently adopted as an objective representation and comparison standard. The current study demonstrates that there is a biasing potential of slow-motion replays when assessing foul-play situations. Slow motion can, for example, increase the probability for penalizing an offender with a red card instead of a yellow card. These findings are of particular relevance for all stakeholders in sports and refereeing. Slow motion is a separate viewing mode and it can alter the result of crucial decisions, thereby impacting on the final outcome or perceived justice throughout and after a game. Consequently, we discuss clear and consistent guidelines regarding when and how slow-motion replays can be used and the link with basic perceptual and cognitive functions.Referees in team sports are responsible for interpreting and enforcing the specific rules of the sport from a neutral point of view. They have to take into account several sources of information and make up their mind to maintain fair play and protect the players’ safety , judgments of referees require subjective evaluations to determine the intentionality of the offence and the disciplinary sanction for the offending player. According to the Laws of the Game FIFA, , severalFans, players, sport commentators, and journalists increasingly rely on video replays, which are often played in slow motion, to evaluate and discuss the referee decision. During decision-training and feedback sessions, referees are also exposed to video replays in slow motion. The use of video technology has already found its way into several sports such as field and ice hockey, cricket, tennis, and basketball to assist the referee and improve decisional accuracy. Here, video technology is used to evaluate whether a goal was validly scored, to determine whether a ball was in or out, or to reconsider foul-play situations. Interestingly, most decisions for which video technology is currently used involve situations for which fairly to clearly objective criteria exist. As such, video technology can effectively increase the accuracy of referee decisions during the game by allowing certain situations to be reviewed from various perspectives and/or replay speeds. Indeed, in field hockey and cricket, video referees have access to replays at different replay speeds and they can use (a combination of) different speeds to arrive at a decision.Although slow motion is commonly used in video refereeing, it is currently unclear to what extent the use of variable video speeds impacts decision-making by referees. The relevance of this question was emphasized by a recent study of Caruso, Burns, and Converse . Here, tLorains, Ball, and MacMahon  showed tThe previous studies focused mostly on decision-making by athletes or assistant referees in situations for which a more or less objective ground truth  can be determined. To date, only a single study assessed whether slow-motion replays impact the decision-making process of association football referees in more ambiguous situations such as foul-play situations  derived from real, international football matches. As in Spitz et al. , we reliIn addition to the applied significance of the current study, this experimental task also taps into the process of the perception of causality . This line of work goes back to the Gestalt psychological tradition  participated in the experiment, yielding a response rate of 63%. All were top-class referees active in European professional football. They provided informed consent and the study was approved by the local University ethics committee (G-2015 04 218).(i)the foul-play situations are represented well in the video clip, as recorded from an in-game perspective the position of the players is clear, most of the time even in the middle of the field, to exclude the influence of the position or situation in the game;(iii)the players are always clearly distinguishable.A total of 60 realistic and representative video clips of tackle incidents were selected. These foul-play situations were taken from matches of the UEFA . We took particular care in selecting specific video clips, in accordance with the following criteria:Each video clip was edited by using two software programs . We manipulated the original video clips as follows: either we reduced the speed of a real-time video clip four times or we increased the speed of a slow-motion video clip four times. The video clips were cut down to the essential fragment to be able to come to a correct decision. This resulted in two identical video clips for each situation, 60 video clips in real time (mean duration 3.08 s) and the same 60 video clips in slow motion (mean duration 12.32 s). The same information was present in both video speed conditions, only the temporal dynamics were modulated. The video clips are MP4 files (720 × 406 pixels), with good quality and with the background sound removed. Two independent and experienced ex-international referees, still involved as referee match observers for UEFA, determined the reference decisions based on the rules established by Law 12: Foul and Misconduct FIFA, . Both moThe experimental video clips were presented to the participants via a web-based application (perception4perfection), developed by the research unit “perception and performance” of the KU Leuven to be used for perceptual-cognitive skills training and research. All participants received an account with an individual login and password to enable them to assess the different situations at their own place. Each referee assessed 60 unique situations. Half of the participants – randomly selected – evaluated 30 situations in real time and 30 situations in slow motion. The other half of the group evaluated the same situations but in the different video speed condition . Three different video clips were used for familiarization with the test. During the test, every slow-motion video clip was followed by a real-time video clip (and vice versa) and after every 20 video clips there was a break. The participants watched each video clip just once, either in real time or slow motion. After every video clip, the referees had to assess whether a foul occurred  and they had to indicate the disciplinary decision  within a time window of 10 s by clicking on the mouse. After clicking, no correction was possible and there was no feedback. The referees were asked to assess the 60 situations, which took approximately 20 min, all on the same day.tidyverse package  and RStudio . For data processing, we relied on the Wickham,  and for Wickham, . All cumDue to the low number of no foul technical decisions, we decided to analyze the disciplinary decisions only. We collapsed the no foul and foul/no card situations into a no card category. Thus, all analyses pertained to disciplinary decisions that could take on the value no card, yellow card, or red card. We evaluated the performance of the referees in two different ways (cf. two aims formulated earlier). First, we computed a simple accuracy measure (i.e. whether the decision was the same as the reference decision or not) to test whether video speed influenced the accuracy of the decisions. It should be noted that this measure of accuracy is merely a reflection of how strongly the referee and reference decisions overlap, rather than being a quantification of how good the referees are at determining a certain objective characteristic of the video clips. An accuracy score was calculated for each video speed and referee; a paired t-test was used to examine differences between both video speed conditions (α = 0.05).We complemented the analyses on accuracy with an analysis that aims to model the data directly and can take into account other aspects of the data, such as the direction in which the decision of the referees shifted. This statistical method is known as cumulative link mixed modeling or mixed ordinal regression. A mixed model allows to simultaneously model different sources of random variability present in the dataset. Importantly, for our experiment, these random effects comprise referees and stimuli. We always included random intercepts for both referees and stimuli, as well as random slopes of video speed condition for both referees and stimuli, and random slopes for reference decision for referees. This was the maximal random effects structure that guaranteed stable convergence during model fitting . ϑj are known as cut-points or threshold parameters. The inverse logits of these threshold parameters indicate the baseline cumulative probabilities for a response ending up in a certain category (or lower) when all predictors are set to zero. In our case, this implies baseline cumulative probabilities for the clips belonging to the no card reference condition shown in real time (see the “Results” section for an example using the estimated threshold coefficients). The sign of the regression coefficients for reference decisions and video speed indicates how the cumulative probabilities are influenced. For example, positive coefficients indicate that the value of these predictors is associated with a higher category rating (i.e. a more severe decision).We model the cumulative probability of the p = 0.11).As can be derived from the scatterplot in Fig. As highlighted in the “Data analysis” section, we used a top-down model selection approach starting with the most complex model, and reducing it in complexity until the drop-in-deviance test indicated that there was no longer a benefit to simplifying a model. Table Thus, Table An increasing number of competitive matches in professional sports are recorded on video and referee decisions are retrospectively analyzed by coaches, fans, players, and sport commentators using slow-motion replays. In March 2018, the International Football Association Board (IFAB), the game’s law-making body, approved, with immediate effect, the use of video assistant referees in association football. A video assistant referee has to check every situation to examine whether a potential clear and obvious error has been made in a match-changing situation. The video assistant relies on video clips in slow motion and/or real time for that. The video assistant referee eventually informs the main referee who then has the opportunity to review footage on the field before making a final decision. It is often acknowledged that slow motion distorts reality and can change the way body movements and intentions are perceived  may be deceptive because it is not always a good indicator of what people are doing and does not provide a complete and comprehensive account of performance differences. The decisions that yield a given accuracy level may encompass extremes of liberal and conservative biases. To gain more insight into the underlying mechanisms of slow motion on the perception of foul play and to determine how the decisions deviated from the reference decision, we performed a mixed ordinal regression analysis. As such, we were able to determine whether the speed of the video replay biased the decisions in a certain direction.The results indicate that slow-motion video clips are associated with increased odds for choosing a higher category on the decision scale . In case of high-impact tackle incidents, there is a clear impact of slow motion, altering the judgment of the referees towards more severe disciplinary sanctions for the offending players. These results are in line with previous research investigating the way replay speed affects human judgment in the courtroom. Viewing a situation in slow motion, compared with regular speed, increased the perceived intent of a violent action  referees more and more make use of technology and they only see videos and replays in slow motion. Despite the fact that referees on the field of play have to decide in real time, these slow-motion replays are adopted as objective representations of the foul-play situations. However, our results demonstrate that it is important to take the biasing potential that results from the artificial distortion of temporal dynamics into account when assessing foul play situations. Slow motion can make the offence look more pre-meditated than it actually was and can, for example, change the disciplinary sanction from a yellow card into a red card.Slow motion can therefore not be seen as a valid basis of comparison and we recommend to only use real-time footage for judging the amount of risk for the opponent’s safety involved and the perceived impact/intent of a tackle. Reminding people that they are watching a slow-motion situation might not be sufficient since previous research has shown that even when people are aware that there is an incidental influencing factor (e.g. slow motion), they often do not correct sufficiently  were available to determine the reference decisions and we were not able to verify whether the expert panel based their reference decisions more on the slow motion rather than on the real-time presentation mode. A potential alternative interpretation of our results could thus be that the influence of slow motion on referee decisions reflects that they converge towards the expert panel decisions. We see two arguments that counter this alternative interpretation. First, it has been shown that showing an action at both regular and slow-motion speed is effective in reducing the possible biasing influence of slow motion  has given rise to training programs where assistant referees are taught to cognitively compensate for their perceptual mistakes , reckless (yellow card), or with excessive force (red card). Therefore, caution is warranted before adopting video technology and clear guidelines should be defined Collins, . Our fin


Oral magnesium supplementation is commonly used to support a low magnesium diet. This investigation set out to determine whether magnesium in a cream could be absorbed transdermally in humans to improve magnesium status.2+ cream intervention there was a clinically relevant increase in serum magnesium  that was not seen in the placebo group (0.77 to 0.79 mmol/L), but was only statistically significant (p = 0.02)) in a subgroup of non-athletes. Magnesium urinary excretion increased from baseline slightly in the Mg2+ group but with no statistical significance (p = 0.48). The Mg2+ group showed an 8.54% increase in serum Mg2+ and a 9.1% increase in urinary Mg2+ while these figures for the placebo group were smaller, i.e. +2.6% for serum Mg2+ and -32% for urinary Mg2+. In the placebo group, both serum and urine concentrations showed no statistically significant change after the application of the placebo cream.In this single blind, parallel designed pilot study, n = 25 participants  were randomly assigned to either a 56mg/day magnesium cream or placebo cream group for two weeks. Magnesium serum and 24hour urinary excretion were measured at baseline and at 14 days intervention. Food diaries were recorded for 8 days during this period. Mg test and placebo groups’ serum and urinary Mg did not differ at baseline. After the Mg2+ in human subjects. In this pilot study, transdermal delivery of 56 mg Mg/day  showed a larger percentage rise in both serum and urinary markers from pre to post intervention compared with subjects using the placebo cream, but statistical significance was achieved only for serum Mg2+ in a subgroup of non-athletes. Future studies should look at higher dosage of magnesium cream for longer durations.No previous studies have looked at transdermal absorbency of MgISRTN15136969ISRCTN registry ID No.  However, subjects in the Mg2+ group showed slight rises in urinary Mg2+ (+9 to 11%) while those in placebo group showed a substantial decrease in urinary Mg2+ (-32%). Possibly the decreased urinary Mg2+ excretion in the placebo cream group represents more active physiological Mg2+ retention processes that are not apparent in the Mg cream group  showed a larger percentage change in both serum and urinary markers from pre to post intervention compared with subjects using the placebo cream. In addition, the rise in mean serum Mg2+ seen in the Mg2+ group was clinically relevant although only statistically significant (p<0.05) when non-athletes were analysed separately.No previous studies have looked at effects of transdermal Mg2+ of these subjects, we suggest that future research focus on a larger number of human subjects given higher concentrations of Mg2+ cream application administered for longer durations to investigate whether transdermal application may show a significant contribution to improvement in magnesium status. It would also be of interest to look at the effect of transdermal Mg2+ supplementation on athletes as compared to a sedentary population group.Given the high variance in serum MgS1 Textlist.Ingredients for magnesium and placebo creams (DOCX)Click here for additional data file.S1 FigChecklist of information to include when doing a randomised trial.(DOC)Click here for additional data file.S1 TableSubject data.(XLSX)Click here for additional data file.S2 Text(DOCX)Click here for additional data file.