There is an urgent need to develop an evidence base for children’s palliative care (CPC) globally, and in particular in resource-limited settings. Whilst the volume of CPC research has increased in the last decade, it has not been focused on countries where the burden of disease is highest. For example, a review of CPC literature in sub Saharan Africa (SSA) found only five peer-reviewed papers on CPC. This lack of evidence is not confined to SSA, but can be seen globally in specific areas, such as an insufficient research and evidence base on the treatment of pain and other symptoms in children. This need for an evidence base for CPC has been recognised for some time, however without understanding the priorities for research in CPC organisations, many struggle with how to allocate scarce resources to research.The International Children’s Palliative Care Network (ICPCN) undertook a Delphi study between October 2012 and February 2013 in order to identify the global research priorities for CPC. Members of the ICPCN Scientific Committee formed a project working group and were asked to suggest areas of research that they considered to be important. The list of 70 areas for research was put through two rounds of the Delphi process via a web-based questionnaire. ICPCN members and affiliated stakeholders (n = 153 from round 1 and n = 95 from round 2) completed the survey. Participants from SSA were the second largest group of respondents  followed by Europe.A list of 26 research areas reached consensus. The top five priorities were: Children’s understanding of death and dying; Managing pain in children where there is no morphine; Funding; Training; and Assessment of the WHO two-step analgesic ladder for pain management in children.Information from this study is important for policy makers, educators, advocates, funding agencies, and governments. Priorities for research pertinent to CPC throughout the world have been identified. This provides a much needed starting place for the allocation of funds and building research infrastructure. Researchers working in CPC are in a unique position to collaborate and produce the evidence that is needed. Palliative care should be available to all children who need it, regardless of where they live, their culture, nationality, or stage of illness. Yet there are at least an estimated seven and a half million children who need palliative care  and in mIt has been well documented that there are many challenges to the provision of palliative care for children including a lack of education for families and providers; limited resources; lack of evidence; limited access to medications - including opioids for pain treatment- and the lack of appropriate policies to ensure availability and access within the health care system , 5, 6.As the demand for CPC increases globally, there is a need to develop an evidence base in order to strengthen services . This isMoreover, there is a desperate need to establish methodologically robust evidence on how best to deliver palliative care in resource-limited settings . This waThree studies have looked at research priorities in CPC at the national level, in Scotland , 17, CanThus, whilst these studies –19 have The Delphi method was used to identify and prioritise areas for research into CPC  as this Step 1: Baseline list of priority areas for research into children’s palliative careThe four steps of our Delphi study are described below.Members of the working group were asked to suggest areas of research that they considered to be important in CPC. An initial list of broad themes for research was provided based on the toolkit for CPC  Fig. 1)1). The ti.Research is urgently needed in that area.ii.There is a gap in the existing evidence in the area, or there is no evidence in existence.iii.Research in the area will impact, either directly or indirectly, on the quality of life of children requiring palliative care and their families.Working group members were informed that in order to recommend an area of research as a priority, it had to meet the following criteria:Step 2: List of participantsFollowing content analysis, similar responses from working group members were grouped together to ensure that the questionnaire was not repetitive and could be easily completed. Content analysis was undertaken in order to identify themes for research and reduce the number of items to a manageable number for the Delphi process , 28. ConStep 3: Delphi processOnce the initial list of priorities was created, invitations to participate in a survey were sent to all ICPCN members and ICPCN board members, who were also asked to recommend individuals in their countries/regions that could complete the survey. This sampling technique was used with the goal of having a geographically balanced group of respondents, including participants from developed and developing countries.A list of 70 research priorities suggested in the first step were put through two rounds of the Delphi process. An online survey was set up using SurveyMonkey, through which participants could access information anonymously and rate the suggested research priorities.Top priority – urgently needs to be done within the next 24 months.High Priority – needs to be done within the next 24–48 months;Medium priority – needs to be done within the next 4–6 years;Low priority – needs to be done but can wait.Not a priorityParticipants were asked to place an X in the box which they felt best described how important the research topic is. The response choices were:Do not know/Not sure’ option if they did not feel comfortable rating the priority. Information as to how the list of suggested areas for research was built was provided to the participants and an opportunity was given to participants to suggest other areas for research that they strongly felt should be incorporated into the list . Participation in the study was voluntary and completion of the survey was taken as consent to participate. Reminders were sent to participants at fortnightly intervals, along with a reminder through the ICPCN newsletter/website. Summary statistics were run on the results to determine the number of statements that had reached consensus at this stage. Consensus was deemed to have been reached if the percentage of answers scoring 1 (top priority) or 2 (high priority) was above 75 %. It was also agreed that the mean score should be <2 for the area of research to be considered a priority.Respondents were also given a ‘The research team reviewed the responses and any additional topics made by the participants in the first round and the initial list of research topics was revised. Those statements that reached consensus during the first round (i.e. >75 % of the participants agreed on the importance) were ‘banked’ prior to round two, as having already gained consensus .The first round of the Delphi process took place between October and November 2012. In the first round of the Delphi, there were a total of 75 questions, divided into 11 sections. Sections 1–10 were based on the broad areas for research and Section 11 was demographic data. There were 70 closed questions i.e. research topics to be prioritised, 1 open question and 4 demographic questions.In the second round of the Delphi process the responses from the first Delphi round were listed and participants were informed that topics had been removed if 75 % or more of respondents had identified them as a Top or High priority. Several new research topics were included that were identified by participants as missing. The results of the first round of the Delphi process in terms of median, mean and standard deviation were included as information for participants. The same response categories were offered.Step 4: Analysis of the ratingsThe second round of the Delphi took place between December 2012 and January 2013 and had a total of 68 questions, divided into 12 sections. Sections 1–10 were based on the broad areas for research, Section 11 was demographic data and Section 12 asked if they had completed round 1. There were 62 closed questions, 4 demographic questions, a question asking whether they had completed round 1, and a question asking if they would like to receive the results of the study.Those areas of research identified as priorities by 75 % or more of the respondents with a mean of <2 after the two rounds of the Delphi process constituted the top priorities for research into CPC. This list was further narrowed down to the top ten according to level of consensus.Results of the study have been reported on according to the CHERRIES statement for web-based surveys .Twenty invitations to participate in step 1 were sent out and 16 responded (80 %). Of these 16, 3 (19 %) were from low-income countries, 2 (13 %) from lower-middle income countries, 4 (25 %) from upper-middle income countries and 7 (43 %) from high-income countries. Respondents represented a range of professions , had been working in CPC for varying lengths of time and worked in eight countries.The first round of the Delphi process included an ‘open survey’ meaning it was open for each visitor to the survey site and could be forwarded on to others at the discretion of the respondent. Invitations for both rounds of the Delphi study were sent to a total of 758 people. If they chose to participate they were given a unique Identification (ID) number which matched their Internet Protocol (IP) address recorded.The completion rate, or the number of people agreeing to participate (or submitting the first survey page), divided by the number of people submitting the last questionnaire page  was calcAn initial list of 165 areas for research within CPC was identified. The list was refined to 70 through content analysis prior to the first round of the Delphi process.Results from the first round of the Delphi process (Step 3) were reviewed and analysed. Descriptive statistics were run on the data in order to determine the number of statements that had reached consensus and to show the distribution of responses. Consensus was deemed to have been reached if the percentage of answers scoring 1 (top priority) or 2 (high priority) was > 75 % with a mean score <2. The consensus ratings for the different areas for research ranged from 43 % through to 84 %. Seventeen questions (24.3 %) had a consensus rating of >75 %, 41 (58.6 %) between 60 and 75 %, and 12 (17.1 %) under 60 %.The seventeen questions which reached consensus were excluded from the second Delphi round . Thirty-Results from the second round of the Delphi process were reviewed and analysed. 62 areas for research within CPC were graded on a scale of priority. Summary statistics were run on the results to determine the number of statements that reached consensus.The consensus ratings for the different areas for research ranged from 35.9 % through to 78.9 %. Nine areas for research reached consensus therefore making a total of 26 areas in total from both Delphi rounds , none of them fit into the categories of social, spiritual or management and human resource issues, whereas 4, (15.4 %) came under education, 3 (11.5 %) interventions and models of care, 2 (7.7 %) for both legislation and ethics and other, and 1 (3.8 %) under policies and procedures.When narrowing it down to the top 10 research priorities for children identified through this Delphi study, it can be seen that they are linked to psychological issues, clinical care, policies and procedures, interventions and models of care, education and legislation and ethics Table .Table 5TThe aim of this research was to identify and prioritise research areas in CPC. Although this exercise has been done in the past, it has been focused at the national level and not been able to comment on global alignment or variation in the field. Contributions of this study to the literature are described below.Participants in this Delphi study represented more than 50 countries and all regions of the world. From the results it is clear that there is consensus on what is important in CPC and that these priorities were chosen independently by the participants. This is important because oftentimes consensus is reached through round table discussions and there might be a tendency for those from the developing countries to have more input since they would by default have more experience in conducting research. By using this method, with this sample, we are able to identify a list of priorities where each respondent received equal weighting of input.Focusing on the results from the top 10 priorities is interesting. When broken down into broad research categories, there is no singular category that overwhelmed the other, although clinical care had the most priorities. It is not surprising that all four clinical issues were around pain management. It is well documented that treating children’s pain is difficult since not many providers receive formal training, there are myths surrounding the use of opioids, availability of pain medication can be a problem, and many of the pain treatment regimens are not evidence based and/or were developed for adults . This isChildren’s understanding of death and dying was the top priority and lends itself well to multidisciplinary research. A child’s understanding will depend on a variety of factors including their age and developmental stage, their illness, how long they have been unwell, their experience of death in the family, and their culture . Much ofFor the two educational priorities, some progress has been made. While there are many accredited palliative care training programmes, many of them are costly. ICPCN recently developed seven online training modules in CPC. Participants can learn about CPC including issues on pain and symptom management, communicating with children and emotional issues, child development and play, end-of-life care, and grief and bereavement, and receive a certificate once they have completed the courses. Admittedly, these modules are limited in scope and language, although they are currently available in English, Spanish, French, Portuguese, Serbian, Russian, Dutch and Mandarin. However, results from this survey can be used to develop new modules in the areas identified as priorities for research such as models of care. Other organisations can also benefit from the result of this study, which can inform their education agenda. Revising the curriculum is a long-term goal that will require coordination between educational institutions, accrediting agencies, and the health care labour market.When comparing the results of this international study with those done in Scotland , 17 CanaAs with any Delphi study, there are limitations. During the initial stage of identifying research priorities, content analysis was used and this can introduce bias as the researcher does not have the opportunity to discuss their responses directly with participants. To mitigate this the content analysis was shared with working group members who commented on it and changes were made as appropriate. The stability of responses within the study is an important factor, and in particular what happens between Delphi rounds, however as there are no direct ethical issues in this study with regards to the identified priorities, this is not considered to be a significant issue. Parents and patients were not invited to participate although their opinions are certainly important in setting priorities and it is hoped that the opportunity will arise to look at these priorities with an international parent organisation. Finally, no definitions were provided and respondents were left to interpret terms on their own.Despite these limitations, this is the first study to prioritise research needs in CPC. National and international organisations can look to this list for guidance and confirmation as they work through their own initiatives. Listing the priorities is only the first step in a long agenda that must be carefully planned and executed and more work needs to be done in order to ascertain the differences in research priorities between high and low resource settings, or between different continents. As we move forward in making strides in CPC research, it is crucial that we stay family-focused and drive our decisions by evidence when possible.


The subject of whether all girls with central precocious puberty (CPP) require brain imaging is controversial.A review of the major papers concerning this topic published since 1994 was conducted looking primarily at the frequency of occult intracranial lesions, particularly brain tumors, in girls with CPP. While CNS abnormalities are frequently noted (8–15 %), the proportion of previously unknown findings requiring intervention in 6–8 year old girls is very small, in the range of 0–2 %.While MRI should still be done in boys and in girls with onset of puberty younger than age 6 and in boys, ordering an MRI should not be routine in 6–8 year old girls with CPP. Suggestions are made as to how to approach the decision-making process with the parents regarding brain imaging in asymptomatic 6–8 year old girls with CPP. Although there is much evidence that female puberty is starting earlier now than in the past , 2, the It has long been known that most cases of girls with CPP are idiopathic, and estimates during the 1970s and 1980s put this figure at about 80 %. With the widespread use of CNS imaging beginning in the early 1980s, small occult CNS lesions could be detected in asymptomatic girls with CPP, leading to concerns that these lesions, including tumors such as astrocytomas and gliomas, might be missed unless all girls with CPP underwent brain imaging. However, in a 1995 report, Bridges et al at Middlesex Hospital in London  reportedth %ile identified all girls with occult intracranial lesions (OCIL). When the model was applied to a larger group of 443 girls from seven centers in six European countries [th %ile for girls with CPP according to the distribution of values at each center identified all 6 girls with onset over age 6 who had an OCIL, but of those who had an estradiol >45th %ile, only 3 % had an OCIL, still a small proportion. In an editorial accompanying this article, Stanhope reviewed the existing literature on occult intracranial tumors in CPP and concluded that “the previous recommendation of denying neuroimaging to girls with CPP made by Bridges et al can no longer be substantiated. It is unfortunate to miss the diagnosis of an early and treatable hypothalamic tumor, such as an astrocytoma, especially as magnetic resonance imaging does not involve ionizing radiation” [A larger series of patients in a 2000 European study involving 304 girls with CPP who underwent brain imaging found that 18.4 % had a CNS lesion, of which half were previously known. Of the CNS lesions found, 8.5 % were newly discovered, though the number involving neoplasms was smaller , would rountries , the resth %ile cut-off to discriminate idiopathic CPP from CPP due to an OICL, a difficult task.One problem with the approach of using estradiol as a key part of decision-making for ordering brain imaging is that it would still require that imaging be done on nearly half of girls with CPP. Furthermore, estradiol levels are notoriously difficult to interpret. Unlike in males where consistently rising testosterone levels during puberty allow one to estimate how far along in the pubertal continuum a boy falls, estradiol levels are less reliable. Even with the more sensitive assays which can detect levels as low as 5 pg/mL, it is not unusual to find girls who are clearly progressing though puberty with pubertal LH values but estradiol levels which are not elevated, as well as estradiol levels in the range of 30 pg/mL in girls who during follow-up prove to have premature thelarche, not CPP. Also given that different labs use different assays for estradiol, it would fall upon every center to pool enough results to determine their 45CPP may be a sign of central nervous system pathology. Unsuspected intracranial pathology has been reported in 8 % of girls and 40 % of boys without neurologic findings or neurofibromatosis. The percentage of children with unsuspected intracranial pathology decreases with age. Only 2 to 7 % of girls who have onset of CPP between the ages of 6 and 8 years have unsuspected pathology, and only ∼ 1 % have a tumor such as a glioma or astrocytoma. Factors that may decrease the likelihood of finding a tumor include racial/ethnic background, family history of CPP, and adoption.It is controversial whether all girls who develop CPP between 6 and 8 years of age require head MRI. Girls with neurologic findings and rapid pubertal progression are more likely to have intracranial pathology and require an MRI examination (BII).Conclusions: All boys with CPP and girls with CPP at <6 years of age should have a head MRI. In 2007, a conference including pediatric endocrinologists from the North American and European societies was held to produce a consensus paper on the use of GnRH analogues in children. One of the topics addressed was the need for brain imaging in CPP, which appears to be routine in most European centers but is not as consistently recommended for 6–8 year old girls in US centers. The consensus paper  acknowleA 2012 study from Copenhagen reviewed imaging findings in 229 girls with CPP evaluated during a 16 year period between 1993 and 2009 who underwent a brain MRI . Of thesThe most recent study on this topic published in December 2014 presents findings in 182 girls with breast development onset before age 8 and a diagnosis of CPP evaluated at the Bambino Gesu General Hospital in Rome between January 1990 and December 2012 . All hadSo how should we use the ample data from the studies cited above to inform the decision as to whether to order brain imaging in patients with CPP? There is no argument that all boys with CPP, girls with CPP with onset before age 6, and any girl with clinical findings indicating the possibility of a CNS lesion  need brain imaging as the yield of new findings which may affect clinical management is significant. The real issue is what to do about girls with CPP onset between ages 6 and 8 with no CNS-related symptoms, who form the great majority of CPP patients seen by pediatric endocrinologists. While rare girls in this category will harbor an OICL, we should also consider the costs of doing so many brain MRIs or CTs to find such a small number (estimated to be in the range of 1 %) of tumors such as astrocytomas and gliomas which will require surgery. (It should be acknowledged that there is no consensus as to how frequent a serious finding must be to justify expensive imaging studies for many conditions in medicine). Although brain MRIs do not expose the child to ionizing radiation, they are significantly more expensive than CT scans. The average charge in the US in 2014 was $2600, which does not include the charge for the neuroradiologist interpreting the study, as well as sedation which is often needed in children, and IV administration of contrast agents, both of which increase the risk of the procedure. There is also the consideration that ordering a brain MRI increases parental anxiety and may be quite stressful for the child. Furthermore, doing MRIs on girls with CPP at low risk for OICL will result in picking up minor incidental findings like pituitary microadenomas, which as pointed out , are verPart of the reason the incidence of tumors in 6–8 year old girls with CPP is so low in recent studies may be that the incidence of CPP in this age group has increased, as part of a larger trend towards earlier puberty in girls, the cause of which has been much debated but is likely due at least in part to the obesity epidemic . The stuOne issue many of us grapple with is the legal implications of missing a brain tumor in a child with CPP. My approach to this is to point out to the parents that the risk of finding a tumor in an asymptomatic 6–8 year old girl with CPP is at most 1 %, and that I would not recommend brain imaging given that small risk. I have found that most parents do not push for imaging when it is presented that way, but if they cannot live with even that small amount of uncertainty, then it makes sense to order the MRI. However, if they are informed of the small risk and included in the decision-making process, I believe that the chance of medicolegal challenges in the unlikely event that a CNS tumor is eventually found is reduced significantly. We are all well-intentioned providers wanting to provide the best care for our children and their families, but in this situation, routine MRIs in all girls with CPP may not be the optimal approach. Until we have more reliable guidelines to identify the rare child with CPP and an OICL, it may be best to review the available evidence with the parents and get their input before making a final decision on brain imaging.Considering the very low frequency of finding brain tumors which require intervention in 6–8 year old girls with CPP and no CNS-related symptoms, it is proposed that brain imaging not be ordered routinely but discussed with the family after explaining both the benefits and risks as noted above.


We propose a new mechanism and a related device concept for a robust, magnetic field tunable radio-frequency (rf) oscillator using the self oscillation of a magnetic domain wall subject to a uniform static magnetic field and a spatially non-uniform vertical dc spin current. The self oscillation of the domain wall is created as it translates periodically between two unstable positions, one being in the region where both the dc spin current and the magnetic field are present, and the other, being where only the magnetic field is present. The vertical dc spin current pushes it away from one unstable position while the magnetic field pushes it away from the other. We show that such oscillations are stable under noise and can exhibit a quality factor of over 1000. A domain wall under dynamic translation, not only being a source for rich physics, is also a promising candidate for advancements in nanoelectronics with the actively researched racetrack memory architecture, digital and analog switching paradigms as candidate examples. Devising a stable rf oscillator using a domain wall is hence another step towards the realization of an all domain wall logic scheme. Self oscillators show a remarkable property of sustaining oscillatory behavior without being driven by sources that possess inherent periodicity. In the macroscopic world, a few well known examples of self oscillations include the heartbeat, violin string oscillations in response to steady bowing34The interest in dynamics of magnetic domain walls has been active for decades7891011131451617112021field like torque which is typically smaller than the Slonczewski like torque222324Normally, domain wall motion under vertical spin currents is caused by We first provide a theoretical analysis using a rigid domain wall model to find an approximate waveform for the oscillations. We show that the frequency is twice the resonant frequency of a magnet in a magnetic field; while the amplitude is approximately a linear function of the ratio of the hard axis anisotropy and the magnetic field. The oscillatory part of the waveform is independent of the input spin current to a very good degree of accuracy; and hence can be of great technological advantage for accurate oscillatory waveforms. We then also numerically simulate the micromagnetic Landau-Lifshitz-Gilbert equation see  as a verz direction exists throughout the region. Both the regions, z = 0. A possible device realization of the proposal, in which the domain wall self-oscillations may be effectively translated into an alternating current oscillations is depicted in 2930The working principle of the proposed oscillator is depicted in The analysis to follow will be based on m is the magnetization unit vector; γ(>0) is the gyromagnetic ratio; Ms is the saturation magnetization of the magnet; μ0 is the permeability of free space; d is the thickness of the sample  is the vertical spin current density loss which is assumed to be dependent only on z; Hext is the externally applied field; Aex is the exchange energy constant; where e sample ; α is thrces see  given byw is the width of the magnet  period, say T. Note that under such conditions, all the terms in Eq π after the time period. Considering Eq nπ where n is any natural number. We restrict our attention to T = 2π which is what we observe in simulation. Coming back to real time, t, we conclude that rigid domain wall approximation restricts the angular frequency of oscillation to be 2γH  will have a field driven drift until it encounters the region of non-zero spin current. In both the scenarios, the spin current magnitude should be large enough to push back the domain wall or the latter will continue to move indefinitely against the field.In MS is the saturation magnetization and Aex is the exchange energy. We assume a crystalline anisotropy, with its contribution to energy density as To verify the results, we have also performed micromagnetic simulations, details of which are included in the NZ and Finally, we verify the stability of the oscillations by adding noise to the rigid domain wall equations and numerically calculating its quality factor. For simplicity, we assume K for 40 μs for various values of spin current and magnetic field. The power spectral density (PSD) of Z for three values of the applied magnetic field is plotted in kA/m, 10 kA/m and 12 kA/m respectively.where In conclusion, we have proposed a new set up for an oscillator based on the self oscillations of a magnetic domain wall. We found that under rigid domain wall approximation, the oscillatory part of waveform is almost independent of input spin current and the frequency of oscillations is solely governed by the external magnetic field. We also demonstrated a high quality factor giving evidence for the stability of the oscillations. We envision that the simple set up proposed, namely a domain wall subject to a non-uniform vertical spin current will also open up many possibilities for simultaneous write and read out along with the possibility of an all domain wall logic scheme.How to cite this article: Sharma, S. et al. Proposal for a Domain Wall Nano-Oscillator driven by Non-uniform Spin Currents. Sci. Rep.5, 14647; doi: 10.1038/srep14647 (2015).


Unfortunately, the original version of this article  containeAfter publication of our study protocol, we noticed an error at the fifth bullet on page 2 . We descIn the original study protocol we described a sample size calculation in which an average length of hospital stay (LoHS) of 7 days and a standard deviation of 6 days was used. These numbers were based on a study of Borghans et al, in which the LoHS was presented of all patients who were admitted at 69 hospitals in the Netherlands during one year . This coAs a consequence of the matched controlled study design, the SD in our study population might be smaller than the above mentioned SD of 4.8, but we are unable to provide reliable estimates .


The physical mechanisms behind accelerating solar and stellar winds are a long-standing astrophysical mystery, although recent breakthroughs have come from models invoking the turbulent dissipation of Alfvén waves. The existence of Alfvén waves far from the Sun has been known since the 1970s, and recently the presence of ubiquitous Alfvénic waves throughout the solar atmosphere has been confirmed. However, the presence of atmospheric Alfvénic waves does not, alone, provide sufficient support for wave-based models; the existence of counter-propagating Alfvénic waves is crucial for the development of turbulence. Here, we demonstrate that counter-propagating Alfvénic waves exist in open coronal magnetic fields and reveal key observational insights into the details of their generation, reflection in the upper atmosphere and outward propagation into the solar wind. The results enhance our knowledge of Alfvénic wave propagation in the solar atmosphere, providing support and constraints for some of the recent Alfvén wave turbulence models. Alfvénic waves are oscillations that occur in a plasma threaded by a magnetic field and their propagation, reflection and dissipation is believed to be partly responsible for the solar wind. Here, the authors observe the counter-propagating Alfvénic waves that most models require for solar-wind acceleration. It is now well known that the fast solar wind originates from within open magnetic field regions in the Sun's atmosphere, for example, coronal holes, with wind acceleration beginning in the transition region and low corona1234789109127891011The textbook Alfvén wave, first described by Hannes Alfvén, requires the existence of an infinite, homogenous plasma. In this scenario, other perturbations of the plasma can also be categorized neatly as slow and fast MHD waves. The distinct characteristics of Alfvén waves are that they are the sole propagator of vorticity perturbations and magnetic tension is the dominant restoring force, in addition to incompressibility. Conversely, slow and fast MHD waves are characterized by compressibility and do not perturb vorticityAU) has been known for a number of years1819202122232426272829303233The existence of Alfvénic fluctuations far into the solar wind The Sun, on 27 March 2012, had two dominant open-field regions with the southern one more readily identifiable. The southern region is marked by the presence of a coronal hole that has extremely low emission in Fe XIII images of the corona obtained with CoMP . This laTo confirm the presence of open fields in this region, we use the evolving surface-flux assimilation model and potential field source surface (PFSS) extrapolation toolWe focus on the northern open-field region and examine the Doppler velocities in this part of the corona. It is evident from the data that there is a predominantly outward propagating Doppler signal in this region. To analyse the fluctuations in the Doppler velocities, we use two different methods to extract the data in the form of velocity time–distance diagrams . The twof) and wavenumbers (k) in the vertical direction, and the outward and inward propagating signals are decomposed. To analyse the waves, both an f–k diagram . The method explicitly determines the direction of propagation of the waves and assuming that these propagating waves are Alfvénic in nature, the direction of propagation defines the orientation of the magnetic field in the plane of the sky. Building up this picture of orientations over the entire atmosphere, the local direction of the magnetic field is determined.The second method is a more refined version of the first, providing the f–k diagram  that the low frequency waves are more readily reflected than high frequency waves, which is to be expected for coronal Alfvén waves7f∼6–7 mHz. The increase in the ratio for these higher frequencies is likely related to the inward power being dominated by noise for f>6 mHz. The noise in the data has a flat power spectrum and the continued decrease in the outward wave power with frequency >6 mHz leads to the increase in the ratio. The ratio flattens off for f>10 mHz, a sign that the outward power spectra also becomes dominated by the noise. The influence of noise is confirmed upon estimating the contribution of the data noise to the power spectra.The inwardly propagating waves can be seen to have significantly less power, both in the diagrams  and the diagrams . In Fig.∼1/f . At the canopy, a transformation from slow to fast magnetoacoustic waves can occur, with the efficiency of this transformation dependent upon the angle between the magnetic field and the direction of wave propagation. This phenomenon has been well studied in a variety of magnetic field configurations and plasma conditions464748455051p-modes to leak out from the interior into the atmosphere535456p-modes to coronal Alfvén waves to explain the approximate energy content of observed Alfvénic motions in the coronaTheoretical considerations support the idea that p-modes could excite Alfvénic waves in a corona with a cross-field density structuring. However, it is clear from the theory that vorticity perturbations must be excited in the corona by the mode conversion at the transition region; otherwise Alfvén waves would not be produced. In the case of a structured corona, any generated vorticity at the transition region must also be transported and the Alfvénic modes would seemingly be the best choice for this. The observed enhanced power of the coronal Alfvénic waves coincident with the frequency range of the dominant p-mode power may support this but further investigation is required for the confirmation of this hypothesis.We note that the discussed theoretical work455051Moving away from the power spectra, another interesting aspect observed is that the propagation velocities of the outward waves is greater than the inward. Under the assumption that there exists a background outflow, in this case most likely the solar wind, then a simplified relationship describing the Alfvénic waves can be obtained (see Methods),cph is the phase speed of the wave, U is the flow speed and z is the direction parallel to the magnetic field. The propagation speed of the outward (plus) and inward (minus) waves is modified by the presence of the flow. Hence, outward and inward wave speed estimates obtained earlier from the Doppler velocity time–distance diagrams suggest the presence of an outward moving flow with an average speed U=31±7 km s−1. This value is comparable to the spectroscopic estimate of outflows in open-field regions obtained from the transition region and low coronal emission linesHere, −1 at 1.2 This basic process is taken further. Following the same principles outlined for creating Doppler velocity time–distance diagrams, estimates for the outward and inward propagation velocities throughout the corona are obtained , which rels ref. . InteresThe measured properties of the Alfvénic waves, that is, amplitude and propagation speed, are further exploited to gain estimates for the gradients of magnetic field strength and density in the open-field region (see Methods). These gradients are shown in combination with electron density measurements available from CoMP, an analytic model of electron densities in an open magnetic field region from measurements in white lightThe estimated electron density from CoMP is found to follow the expected trend from the analytic model and this is supported by the density gradient obtained from the magneto-seismological inversion. In addition, the magnetic field gradients from the magneto-seismology show good agreement with that predicted by the PFSS. The quality of the agreement between the different measures for the plasma parameters suggests that the physical properties of this particular open magnetic field region are well constrained by this set of observations.−1. This value is significantly larger than CoMP Doppler velocity amplitudes —which can meet the energy flux requirements for accelerating the solar wind assuming δ∼50% . The indication that p-modes could play an important role in wave generation suggests that this assumption would neglect a fundamental physical process.In addition to this, the power spectra reveal insights into the generation of the waves and their propagation. The slope of the power spectra for the Alfvénic waves shows a 1/Currently, the estimates of energy flux from observable Alfvénic  waves in open-field regions advocate that there is insufficient energy to meet the demands for solar wind accelerationThis study also demonstrates the power of magneto-seismology of the solar atmosphere to probe the corona. Using the measured properties of the waves, evidence for the origins of the solar wind are seen in flow maps and significant constraints can be placed on other physical properties of the open magnetic field region, that is, magnetic field strength, density and the gradients of the two quantities. It is hoped that the measurements of the plasma parameters, along with the measured wave properties, for example, amplitude and power spectra, should provide a significant test scenario for models of solar wind acceleration, especially those which focus on MHD Alfvénic wave turbulence.UT to 20:13:02 UT. The details of the acquisition and reduction of the data are fully described in refs ″.46 . The final data product is intensities at three infrared wavelengths , which are positions centred on the Fe XIII emission line at 10,747 Å. The filter has a bandpass of 1.3 Å. Following ref. The data used here were obtained with the CoMPUT to 20:10 UT and processed following standard procedures.We also make use of SDO AIAHere, we describe the two complementary methods for analysing the wave power spectra.″ wide and 125″ tall  and the outward and inward power spectra are determined  is performed and the power for a range of frequencies and wavenumbers in the vertical direction is calculated. The outward propagating motions are decomposed from the inward propagating motions. Averaging the outward and inward power over the different strips, the power is integrated over wavenumber  and mp is the proton mass, 1.67 × 10−27 kg. The electron density measurements as a function of height (stars) are shown in CoMP is able to measure both the 10,798 Å and the 10,747 Å Fe XIII emission lines, the ratio of which is known to be sensitive to the electron number density, 7.0 ref. , electroIn the main text, we discussed the process of estimating the flow speed in the corona via magneto-seismology of the solar atmosphere by exploiting the measured propagation speeds of the waves. This relationship can be obtained from the following equation:η is the perturbation of the displacement, μ0 is the magnetic permeability of free space, and the subscript i and e correspond to quantities inside and external to the waveguide, respectively. The magnetic field inside and external to the waveguide is assumed equal. This equation describes the kink wave in a thin over-dense waveguide in a low-beta plasmaλ∼100 Mm. Looking for plane wave solutions and under the assumption that Ui≈Ue, it is straightforward to arrive at cph equal to the kink speed. The square of the kink speed is given by ck2=B2/(μ0<ρ>), where <ρ>=(ρi+ρe)/2 is the average density.Here, Further information about coronal plasma properties can also be obtained via magneto-seismology of the solar atmosphere, if we exploit measurements of the wave amplitude and propagation speed together. In particular, gradients in the density and magnetic field strength can be estimated69MHD wave theory reveals that the relationship between the measureable quantities and the quantities to be estimated is given by,v is the velocity perturbation amplitude of the wave, ω is the angular frequency, C is a constant and B is the magnetic field strength. Due to the presence of the unknown C, it is only possible to find the gradients of the density and magnetic field strength. The magnitude of the quantities can only be known if we have initial values for both the quantities. Hence, the gradient of each quantity is normalized and can be scaled for comparison with the magnetic field and density estimates measured by other means.where To exploit In addition to the propagation speed, the Doppler velocity amplitude is also required as a function of height. Each velocity time series in the boxed regions is smoothed using boxcar function of length 3. The root mean square (RMS) value of the removed signal due to smoothing is found to match the estimated RMS of the noise, implying that the smoothing isolates the real velocity signal and suppresses the noise. Taking the RMS value of the smoothed velocity signal and averaging, we obtain the Doppler velocity displayed in v∝ne1/4− . Using this expression, the density gradient inferred from the RMS Doppler velocity amplitude (red diamonds) shows good agreement with the analytic density profile =21 km s−1, where kb is the Boltzmann constant, Te is the electron temperature  and mion is the mass of the ion. In addition, the line will be broadened by an instrumental width that has a value of 21 km s−1. The thermal and instrumental widths can be removed from the measured Doppler width to provide the non-thermal width. As with Doppler velocity, the non-thermal width is averaged horizontally over the boxed region and plotted as a function of height in The non-thermal widths of the spectral lines are often used as an indicator of Alfvénic wave activity2021222324SDO/AIA is used to measure the swaying motions of the magnetic field, which can be interpreted as MHD kink waves. The magnetic field is outlined by density enhancements in the corona seen in the open-field region . The meaρ=9.5 × 10−13 kg m−3. In addition, the phase speed at 1.01 To estimate the wave energy flux, we require an estimate for the mass density in the corona. This is determined from extrapolating from the CoMP electron density measurements back to 1.01 The wave energy flux from the non-thermal widths uses the density and value for non-thermal widths at a height of 1.06 How to cite this article: Morton, R. J. et al. Investigating Alfvénic wave propagation in coronal open-field regions. Nat. Commun. 6:7813 doi: 10.1038/ncomms8813 (2015).


Objective: The use of radionuclides in patients undergoing nuclear medicine procedures presents a special concern on the safety of not only the patients but also of those who come in contact with such patients either at the nuclear medicine centre or at home after discharge from the facility. This has heightened the public concern about nuclear medicine especially in Nigeria where the practice is new. When patients are injected with radioactivity for nuclear medicine procedures they excrete most of the radioactivity via urine even before leaving the nuclear medicine facility. Therefore, we set out to survey the toilets used by these patients in the hospital for radiation levels to know the radiation risk posed by the ‘radioactive urine’ of the patients to the general public and radiation workers respectively. Methods: A portable digital radiation survey meter was used for measurement of radioactivity in toilets used by a total number of 202 patients injected with 99mTc-based radiopharmaceuticals over a period of 60 days for the level of radioactivity. Results: The minimum background radiation level measured was 0.18 µSv/h while the maximum was 0.44 µSv/h and the mean background reading was 0.28 µSv/h. The readings recorded for the male toilets were: 0.1 µSv/h minimum, 5.62 µSv/h maximum with a mean of 0.52 µSv/h while those for the female patients were 0.19 µSv/h minimum, 21.73 µSv/h maximum and a mean of 3.3 µSv/h. Conclusions: In conclusion, the radiation levels from toilets used by patients injected with 99mTc-based radiopharmaceuticals were within reasonable and acceptable limits and do not pose significant radiation risk to others.  Nuclear medicine is relatively new in Nigeria with the first nuclear medicine department established in 2006 at the University College Hospital Ibadan. The phobia for radiation which has led to a heightened public concern of medical procedures involving radiation  is still99mTc-based radiopharmaceuticals. The nuclear medicine patient, before leaving the nuclear medicine facility, would have eliminated much of the radiation by both physical and biological decay of the radionuclide. The patients are usually encouraged to drink large amounts of water to aid the excretion of the radionuclide injected from the body and for the attenuation of the radiation dose to the bladder . Since t99mTc-based radiopharmaceuticals. This study was therefore aimed at investigating the radiation levels in the toilets to know the radiation risk posed by the “radioactive urine” to relative of patients (who accompany very sick patients to such toilets), the cleaners and other radiation personnel who come in contact with such toilets in the course of their work. This will enable us review the radiation safety rules in the toilets used by patients undergoing scintigraphy using A portable digital dose rate meter  with a measuring range of 0.1 µSv/h to 100 µSv/h (energy range of 40 keV to 1.5 MeV) and a sensitivity of 0.83 c/s per µSv/h was used to measure the gamma dose rates in the toilets over a period of 60 days. Background readings for gamma dose rate in the toilets were taken, usually between 7.30 - 8.00 am prior to injection of radiopharmaceutical and use of the toilets by the patients for each day during this period. Measurements were also taken at 9.00 am shortly after the patients injected would start using the toilets. Further measurements were carried out at 12.00 pm and 3.00 pm respectively for each day, during which time the use of the toilet would have reached its peak. Toilets used were the normal WC found in most homes in our country and measurements were taken directly above the toilet seat, at the sides of the seat and at 1m from the toilet seat. These were carried out both in the male and female toilets. Tc-based radiopharmaceuticals used the toilets during the period of survey. We had 60 male patients and 142 female patients respectively. The summary of the demographics and amount of radionuclide injected into the patients is shown in A total of 202 patients injected with 99mA total of 1,745 measurements were carried out within the period of survey of the toilets. Worldwide, radiation protection is a very important aspect of nuclear medicine practice ,19,20,21The radioactivity is also contained by the use of toilet facility either at the nuclear medicine centre or at the patients’ home. Usually, the majority of radioactive materials used in nuclear medicine have short half lives. This means that the radionuclides decay to background radiation in a short while. Technetium-99m for instance, has a half life of 6.02 h and this means that in one day (24 h) it would have decayed physically by a factor of 4. So, the period during which the patients stay in the hospital before discharge is enough for much of the injected radioactivity to decay to safe levels. On a general note, radioactivity deposited internally in nuclear medicine patients is not a likely source of significant dose and risk for staff and relatives as it is deemed to be low as long as the patient is not incontinent or prone to vomit ,23. RadiFrom the results of our measurements, we observed that the maximum radiation level recorded was 21.73 µSv/h which in comparison with the above limits, is seen to be within acceptable limits. The highest dose rate measured in the male toilet was 5.62 µSv/h which is far below the limits set for restricted areas, such as the radioactive based toilets. Data obtained from this study also revealed that when the toilets are not flushed, the radiation levels could be two orders of magnitude higher than the dose limits for controlled areas but are less than the dose limits when the toilets are flushed twice after use. The high levels recorded in the female toilets could be attributed to the fact that during the period of survey, the female toilet was more frequently used than the male toilets, since the male patients with catheter did not use the toilets whereas there was no female patient with catheter. It could also be attributed the fact that sometimes, instructions to flush the toilet twice after use were not followed. At the nuclear medicine centre where substantial radioactivity is meant to be excreted, is also the regulation of the need for a delay tank. Furthermore, the issue of delay tank ensures that the public is not exposed to any radiation hazard as the waste is only discharged when the radioactivity would have reached background levels.99mTc-labeled radiopharmaceuticals were within reasonable and acceptable limits and do not pose significant radiation risk to others. However, these radiation levels can further be significantly reduced if radiation safety instructions are properly followed by the patients. Secondly, usage of automatic toilet flushers, which will flush the toilets should the patient fail to follow the instruction to flush twice after use will be of great efficacy especially within the milieu of high illiteracy. We can therefore conclude that the radiation levels from toilets used by patients injected with 99mTc-based radiopharmaceuticals, they would pose no radiation danger to their family members. It could also be inferred from this study that, when patients are discharged home from nuclear medicine facilities after been injected with The authors are grateful to Prof. Mboyo D. T. Vangu of University of Witwatersrand, Johannesburg South Africa for suggesting that we should carry out this work.


Sonotubometry is a non-invasive means of assessing Eustachian tube (ET) function. Its interpretation remains a complex task with questionable results due to wide variation between trials. A study was conducted to ascertain whether the measurement of phase shift in sonotubometric signals would be a more reliable indicator of ET patency than fluctuating Sound Pressure Level (SPL).The ears of six healthy participants and two participants with patulous ET (PET) were probed with a 100 Hz signal. Five recordings of SPL were performed at the external auditory canal. Cross-correlation was performed among filtered SPL signals and among extracted phase shift waveforms. Peak coefficients were averaged to provide a measure of waveform similarity between trials.Mean peak cross correlation coefficient for SPL signal measured 0.603 ± 0.057 Standard Error of Mean (SEM) whilst that for Phase-Shift signal measured 0.884 ± 0.027 (SEM). All normal participants demonstrated an observable phase change between the ear and nasal signal during swallowing indicating an acoustic impedance change during the event. For the PET patients tested, the phase measurements in ear and nasal signals follow one another reasonably closely, indicating little or no impedance change during swallowing. It is thought that this impedance change is indicative of opening of the ET in normal patients, and the lack impedance change indicates ET either remaining open or remaining closed throughout the swallow.Experimental data suggest that phase-shift detection is a more consistent means of interpreting sonotubometric data than SPL analysis. The middle ear, a normally sterile chamber, houses the auditory ossicles which couple mechanical vibrations from the external ear to the oval window of the inner ear. Bordered laterally by the tympanic membrane (TM) and medially by the inner ear, ventilation and pressure equalization are achieved through the periodic opening of the Auditory canal or Eustachian tube (ET) . MaximumPresently, auditory tube dysfunction is subjectively assessed, limiting the ability of physicians to detect the early signs of ET dysfunction and objectively assess the efficacy of surgical and medical interventions. Numerous methods have been proposed to objectively visualize/detect the patency of the ET including manometric methods, and conventional imaging techniques . HoweverThe principles of sonotubometry were first described by Politzer in the late 1800’s who reported increased acoustic transmission from a tuning fork through the Eustachian tube during deglutition . SonotubMany researchers use a chosen (arbitrary) number of standard deviations to classify a recorded section of an SPL signal as either “ET Opening” or “No Opening” . HoweverPhase-Shift detection for sonotubometric interpretation places less emphasis on changes in the sound pressure level transmitted through the ear and instead focuses on changes in the phase shift of the transmitted signal, caused either by changes in the reactive impedance of the ET or by changes in signal delay, resulting from the collapse or opening of cartilaginous walls of the ET.In a 1985 patent issued to Meno  describiTo lay a framework for sonotubometry that is clinically useful (by being easy to interpret) and reliable (by being less susceptible to interference), this study details a method of analyzing sonotubometric data based on phase detection of the measured signal. The reproducibility and interpretability of this strategy is contrasted against that commonly used in the literature to interpret sonotubometry results.Ethics approval for this study was granted by Capital District Health Authority Research Ethics Board. A 100 Hz sinusoidal signal was generated using LabView  and fed to a KRK VXT4 Speaker System  with peak SPL of 107 dB and 45 W power output (frequency response 66 Hz – 22 kHz). The speaker was isolated in a sound proof box and a funnel attached to its diaphragm channeled sound pressure through a ¼” diameter, 1 m long, flexible vinyl tubing to pass sound into an isolated soundbooth. The transmitted signal was captured through a Etymotic Microphone (transducer) placed in the external auditory canal and digitized by a USB-2404  24-bit data acquisition system (DAQ) sampling at a rate of 5 kHz and recorded over a 5 s time course. Five separate measurements were performed for each healthy participant. Despite Virtanen’s conclusion that frequencies above 5–6 kHz may be the best to probe for sonotubometry , for a sSix participants from the EAR/SENSE lab and two participants from the ET clinic had their measurements taken in the sound booth. The six participants from the EAR/SENSE were otologically healthy and reported no history of chronic ear infection, vestibular dysfunction, nor did they report symptoms of patulous ET or hypofunctioning/insufficient ET. They correspond to Ears 1 to 6. The two participants with PET correspond to Ears 7, and 8. The stimulus was presented to an open nostril and an Etymotic microphone was placed in the contralateral nostril to record the stimulus. Another Etymotic microphone was placed in the ear ipsilateral to the stimulus. Participants were given a glass of water and were signaled to swallow at 1 s following the initiation of recording. For each ear, this process was performed 5 times. The same process was performed on a patient with severe PET confirmed by visualization of TM motility with inspiration.th order Butterworth Filter with a passband 10 % below and above the frequency of interest (pass band = 90–110 Hz).Experimental data were subsequently processed in MATLAB . Signal recordings from both the contralateral nostril and ipsilateral ear were passed through a digital 10The filtered SPL signals were segmented into 10 ms lengths – equal to the period of the 100 Hz stimulus signal. Phase of each 10 ms long segment was calculated and entered as a data point in a new phase array producing 500 datapoints (100/s) over the 5-s long time course. The mean of this array was then subtracted from each data point in the array. Each participant ear yielded 5 SPL signals and 5 phase-shift arrays.The five sets of measurements from each patient were compared with one another to yield 10 different cross-correlation products for each of the filtered SPL output and the Phase Shift outputs. Similar waveforms yield higher peak cross-correlation values than dissimilar waveforms. In this manner, the average peak cross-correlation value for a series of waveforms is indicative of the repeatability/stability of the system that produced them. This “system” includes the act of swallowing, nasopharyngeal acoustic changes, and the detection method for the data. Both the amplitude data and the phase data share a common denominator by virtue of being produced by the same set of actions and being captured by the same equipment simultaneously.Figure Figure Figure p < 0.05, unpaired t-test), the peak cross-correlation coefficient in phase is greater than that in SPL.For each participant ear, the maximum values from each cross-correlation trial were averaged. Across all participants, mean peak cross correlation coefficient for SPL signal measured 0.603 ± 0.057 (SEM) whilst that for Phase-Shift signal measured 0.884 ± 0.027 (SEM). Figure These patients with PET illustrate that an increase or peak in SPL can still be achieved with swallowing but there is no sudden phase separation. We do not see the characteristic phase dip seen on the graphs from healthy patients.Overall, the results of this experiment show that the difficulty of interpreting sonotubometry data is compounded by the variability in SPL levels and highlights the comparative relative stability of phase data.Sonotubometry is an attractive clinical tool, yet remains widely unused in such settings. Previous attempts have used the detection of SPL and their standard deviation from the mean to infer the state of the ET, however the SPL of the test tone may or may not be consistent in the nasopharynx thus complicating the interpretation of the SPL data at the external auditory canal. Sinusoidal signals have been the predominant signal used to probe the ET and although the phase of these signals may be influenced by a number of factors, our early results suggest that the influence and the resultant measurements are more consistent than signal amplitude or SPL.The work presented in this paper models the nasopharyngeal region, ET and middle ear as compliant chambers in series and highlights the possible utility of using dynamic/shifting phase differences to determine the state of the ET and the degree to which it is open. Using a low frequency (100 Hz) probing signal and a DAQ to capture SPL at participants’ ears and noses, notable deviations were observed when the participants were instructed to swallow. In the majority of otologically healthy patients, a negative phase shift occurred during the swallowing motion. The phase detected at the ear deviated sharply from the phase measured in the nose which itself remained relatively flat. This shift may be indicative of decreased impedance experienced by the transmitted acoustic signal (presumably through opening of the ET). However, it could also be due in part to stiffening of the tissue sound bridge (e.g. the articulation of the Temporomandibular Joint), the movement of the soft palate, the movement of the tongue, muscles of the larynx, the temporarily increased pressure in the nasopharyngeal cavity, etc. The nature and magnitude of the contribution of the ET to this phase shift is yet to be determined and is the subject of further research.The phase shifts measured at the ears and noses of the subjects with confirmed PET differ from those of healthy subjects in that the nasal phase also deviated from the baseline during the act of swallowing. Due to the complex changes that occur in the nasopharyngeal space during swallowing, it is difficult to interpret the significance of this deviation. More meaningful, however, is the fact that the ear and nasal phases tracked together during the act of swallowing – that is, they trended upward and downward in relative unison/synchrony. This synchrony, and upward deflection corroborate the model of directly coupled chambers in PET and could perhaps be one of the discriminating factors to differentiate between PET patients and healthy subjects.Despite the small sample size used in this preliminary study, the results, indicating improved consistency using phase data relative to SPL in sonotubometry, are compelling and warrant further investigation. To the best of the authors’ knowledge, at the time of this preparation there had been no studies detailing phase-shift detection as a strategy for sonotubometry data analysis and presenting experimental results. Yet to be determined are the method’s sensitivity and specificity for transient ET opening and PET which may be accomplished using a detection protocol described by Swarts et al. . With de


Slipped capital femoral epiphysis (SCFE) is one of the most common adolescent hip conditions. Unstable SCFE is characterized by sudden and severe hip pain with the inability to weight bear, even with crutches. Osteonecrosis of the femoral head is increased in patients with unstable SCFE. The aim of our study was to systematically review the literature that compares hip decompression to no hip decompression of unstable SCFE.We searched several databases from 1946 to 2014 for any observational or experimental studies that evaluated hip decompression and osteonecrosis of unstable SCFE. We performed a meta-analysis using a random effects model to pool odds ratios (ORs) for the comparison of osteonecrosis between patients undergoing hip decompression and no hip decompression. We also investigated the type of hip decompression performed. Descriptive, quantitative, and qualitative data were extracted.p = 0.54, I2 = 0 %]. No significant differences in the rates of osteonecrosis were detected in unstable SCFE with open and percutaneous hip decompression alone  or hip decompression with bony procedures .Of the 17 articles identified, nine studies (eight case series and one retrospective cohort study) were eligible for the meta-analysis, with a total of 302 unstable SCFE. The pooled OR = 0.91 of osteonecrosis between hip decompression and no hip decompression was in favor of hip decompression, but was not statistically significant [95 % confidence interval (CI): 0.47, 1.75; The cumulative evidence at present does not indicate an association between hip decompression and a lower rate of osteonecrosis of unstable SCFE. However, hip decompression of unstable SCFE remains an option that can potentially decompress the intracapsular hip pressure and optimize the blood flow to the femoral head. Thus, multicenter prospective cohort studies are required and will be able to answer this question with more certainty and a higher level of evidence.Level III/IV. Slipped capital femoral epiphysis (SCFE) is one of the most common adolescent hip conditions that have potential long-term sequelae and are dependent on the severity of the SCFE . SCFE caThe management of unstable SCFE remains controversial, with little consensus on the best treatment and with most recommendations made with level IV evidence . HoweverOsteonecrosis of the femoral head is the most significant complication in patients with unstable SCFE. The rate of osteonecrosis varies between studies and has been reported to range from 3 to 58 % . A recenThe aim of our study was to systematically review the literature that compares hip decompression to no hip decompression of unstable SCFE. The primary outcome analysis involved the rate of osteonecrosis of the femoral head.A senior medical librarian with 40 years of experience developed the search strategy and performed the literature search. The databases that were searched included Ovid MEDLINE (1946 to August 2014), Ovid EMBASE (1988–2014), Web of Science, Elsevier Scopus, and the Cochrane Registry of Clinical Trials. The primary terms were “slipped capital femoral epiphysis” combined with “unstable”, “avascular necrosis”, and “osteonecrosis”. Articles were not limited to any particular study design. Two authors independently assessed the eligibility of the identified studies. Any study that could be relevant based on the respective abstract was reviewed in full text. Bibliographies and review articles were reviewed manually for additional citations. The language of the publications was restricted to English. We did not seek unpublished investigations.We considered any study design that compared hip decompression and no hip decompression of unstable SCFE and reported the rate of osteonecrosis of the femoral head. An unstable SCFE was defined as a patient with pain so severe that walking was not possible even with crutches, regardless of the duration of symptoms according to the Loder et al.  classifiTwo authors independently extracted and recorded the required datasets, which included study characteristics , mean age of patients, number of unstable SCFE, method of reduction and treatment of unstable SCFE, and the number of cases of osteonecrosis of the femoral head. Two authors independently assessed the methodological quality of retrospective cohort studies according to key validity components that address selection, comparability, and exposure using the Newcastle–Ottawa Scale  to assesI2 statistic. This defines the variability percentage in effect estimates that is due to heterogeneity rather than to chance; the larger the I2, the greater the heterogeneity.We pooled studies and constructed Forest plots using the DerSimonian–Laird random effects model , which rWe based the main meta-analytic comparison on the odds ratio (OR) of the osteonecrosis rate in patients undergoing hip decompression versus those undergoing no hip decompression. The osteonecrosis rate was obtained by dividing the number of unstable SCFE that developed osteonecrosis of the femoral head by the total number unstable SCFE. The diagnosis of osteonecrosis was defined by clinical and radiological findings. If no event occurred in at least one cell of the (2 × 2) contingency table for a parent study, a continuity correction of 0.5 was added to each cell to compute the OR and permit analysis, as described in the Cochrane handbook .A further sensitivity analysis was performed with the inclusion of the study by Kallio et al. . AdditioThe search strategy yielded 317 publications, of which we considered 17 articles for full-text review. We excluded four systematic reviews and a further four not fulfilling our inclusion criteria of unstable SCFE and not reporting the rate of osteonecrosis in patients undergoing hip decompression compared to those with no hip decompression. A total of nine studies addressing hip decompression versus no hip decompression were eligible , 15–22. Table Table p = 0.54, I2 = 0 %], which suggested a lower rate of osteonecrosis in patients who had hip decompression, but this difference was not statistically significant. The rates of osteonecrosis in the hip decompression and no hip decompression groups were 16.2 and 22.2 %, respectively.Figure p = 0.77) was not significant for publication bias.There was no evidence of publication bias from the funnel plots, and the Egger test    Fig.  for unstI2 = 30.9 %; p = 0.16) and no significant changes in the overall results.Sensitivity analysis with the inclusion of the study by Kallio et al. , which rHip decompression was associated with a 16.2 % pooled rate of osteonecrosis of the femoral head compared to 22.2 % for no hip decompression in patients with unstable SCFE. The current study revealed no statistically significant difference in the observed rate of osteonecrosis in unstable SCFE when comparing hip decompression and no hip decompression. The results were consistent across different assumptions. The extent to which this statement reflects the true outcome of comparison requires an understanding of the limitations in the current literature and included studies and consideration of the conduct and interpretation of the results of the analyses. The ability to detect a difference is further confounded by the relatively small sample size. Although our study assessed the effect of hip decompression, there was varied reporting regarding the key determinants of unstable SCFE known to influence the rate of osteonecrosis, and none of the included studies reported effect estimates adjusted for these potential confounders.Intracapsular hip pressure is increased after traumatic femoral neck fractures and, thus, increased intracapsular hip pressure is a known cause of osteonecrosis in femoral neck fractures in children , 25. DecParsch et al.  observedThere is currently no comparative study demonstrating the superiority of decompression over no decompression in terms of lowering the intracapsular hip pressure of unstable SCFE and preventing osteonecrosis of the femoral head. Surveys of both the European and North American pediatric orthopedic societies showed that hip decompression was recommended by 29 % of European and 35 % of North American pediatric orthopedic surgeons . Our sysOur findings are consistent with the literature, with an overall rate of osteonecrosis of 19.5 %. We found that hip decompression was not associated with a lower rate of osteonecrosis in patients with unstable SCFE. Sensitivity analyses revealed no significant change in the OR of osteonecrosis when no bony and bony procedures were performed with hip decompression in unstable SCFE. However, orthopedic surgeons may consider hip decompression of unstable SCFE as an option that can potentially decompress the intracapsular hip pressure and optimize the blood flow to the femoral head.Our analysis has a limitation due to the paucity of studies addressing this pivotal issue. There were only nine eligible published studies, but we chose to perform the meta-analysis to provide more generalizable results on the effect estimate. The only outcome measure examined in this meta-analysis was the rate of osteonecrosis. This is a clinically relevant and important outcome and the definition of osteonecrosis was the same amongst the nine studies. Other important factors, such as the time of intervention, the role of reduction, the type of fixation, and post-operative management, could not be controlled for in this analysis and require further study. The limited number of studies addressing these factors permits limited conclusions from the current study. These factors will particularly vary from center to center and variations in clinical skill, implant use, and patient assessment will further confound the results because of these inconsistencies. In addition, others have expressed a concern regarding the different and variable definitions for stable and unstable SCFE . HoweverThere has recently been a change of approach to unstable SCFE with urgent reduction, decompression and fixation or open reduction, and fixation using surgical dislocation. The rate of osteonecrosis has been reported to be as low as 8 %, but larger series are required in order to determine the safe approach to unstable SCFE using these surgical techniques . DespiteOur study has only assessed the effect of hip decompression on the rate of osteonecrosis for unstable SCFE, which is one of many factors that may influence osteonecrosis. Hence, the cumulative evidence at present does not indicate an association between hip decompression and a lower rate of osteonecrosis for unstable SCFE. However, orthopedic surgeons may opt to decompress unstable SCFE to decrease intracapsular hip pressure and optimize the blood flow to the femoral head. The results of our meta-analysis are based on observational studies and, thus, further attention should be directed to studies of good methodological quality. Therefore, multicenter prospective cohort studies are required and will be able to answer this question with more certainty and a higher level of evidence.


A cohort study was planned to evaluate vaccine immunogenicity and effect of malaria and helminth co-infections on the bivalent Human papilloma virus (HPV) vaccine. The study would involve self collected introital swabs, blood draws and stool sample collection. We therefore conducted a pilot study to assess the acceptability of these procedures among the students and their parents.A cross-sectional study among forty four students from two purposively selected primary schools of Western Uganda. Exit interviews and two focus group discussions (FGD) (for parents) were conducted. Acceptability was measured by willingness to undergo the procedures again, recommending the procedures to others as well as proportion of introital swabs positive for β globulin. FGD determined acceptability of the parents and explored opinions and perceptions that would influence their decisions. HPV-16/18 and β globulin deoxyribonucleic acid (DNA) were analysed using a polymerase chain reaction (PCR) kit. All the students (100 %) in the study were willing to provide a self- collected introital swab and a stool sample as well as recommending their friends while (86.3 %) were willing for blood draws. There were 40/44 (90.1 %) self collected introital swabs that had positive result for human β globulin though none of them was positive for HPV-16/18. In the FGD, it emerged that parents concerns were on the blood draws and introital swab collection which were addressed.The study procedures were highly acceptable among this study population of students and their parents. Follow-up to assess HPV vaccine effectiveness and factors that may influence the vaccine in this age group is feasible.The online version of this article (doi:10.1186/s13104-016-1984-8) contains supplementary material, which is available to authorized users. Cervical cancer is the second most common malignancy among women worldwide and the commonest cancer among—Ugandan women , 2. HumaThe available vaccines against HPV infection are almost 100 % effective in preventing infection and high-grade pre- cancerous lesions associated with the HPV-16/18 included in the bivalent vaccine . About 4In addition, the duration of protection and need for booster doses are not known, therefore, there is need for continued monitoring of vaccine immunogenicity and effectiveness over time .A study was therefore conceptualized to evaluate vaccine immunogenicity and effect of malaria and helminth exposure on the vaccine in Uganda. This study would require multiple invasive and private procedures; blood draws, self-collected vaginal swab and a stool sample. Acceptability of self collected vaginal/introital swabs has been well documented . HoweverWe conducted a cross section study in February 2011. Study participants were students aged 10–16 years from two Western Ugandan districts of Ibanda and Mbarara. HPV vaccination had taken place in Ibanda district and none in Mbarara. Ibanda district had about 272 primary schools while Mbarara district had 402 primary schools according to the district records. We purposively selected two neighboring schools one from each district that were near each other and near the road with at least 20 students in primary five. All the students from the two selected schools in primary level five were eligible to participate. The head teachers from these schools were contacted and detailed explanations about the study were given. Prior appointments were made for the teachers to request the parents/guardians of the students to come to the school. Presentations and discussions were held with the, parents/guardians as well as the students in separate sessions. These included information about the HPV vaccine; need to assess its effectiveness and the study procedures the students would undergo. Parents/guardians who consented and with their students’ assent were included in the survey. After the consent and assent, study numbers were assigned serially and a plaster bearing the number was placed on the left arm of the participating students. Students who were menstruating were excluded.A demonstration was given to the students on how to collect introital swabs by the principal investigator in the classroom. Students were instructed to wash their hands. In a squatting position with a Dacron swab the students were to open the swab by the end of the handle, rotate it around the introitus while counting up to 10 and then place it in a labeled sterile tube. With the above instructions, in the privacy of a restroom, the students self-collected an introital swab and returned them to the research assistants.from the rest room. After collecting the stool, it was immediately examined by two skilled technologists using the Kato-Katz method [The students were requested to place a stool sample of about a teaspoon on a polythene sheet bearing their unique number by use of a wooden spatula z method  for presmls) of blood were aseptically collected from the cubital vein into a labelled serum separator tube (SST™) tube.The study laboratory technician, carried out the blood draws from the students. In a sitting position, the girl’s non dominant hand was identified. Following identification of the vein in the cubital fossa, the area was cleaned with 70 % alcohol swab. Five millilitres  of Tris Ethylenediaminetetraacetic Acid (EDTA) buffer for 2 min and vigorously vortexed to remove the swab material. The solution was transferred in a new tube and centrifuged and the supernatant was discarded. DNA was isolated from 100 µl of the remaining sample and HPV-16/18 genotyping was done by a commercial multiplex Real Time amplification according to the manufacturer’s instructions . The PCR reaction involved primers for the human β globulin gene as an internal control. Samples that were negative for β globulin represented non compliance from the student to collect the sample.After the swab, blood and stool samples were collected we conducted exit interviews of all the students who had participated in the study were conducted to measure acceptability of the procedures by the students. The interviews were administered by use of an interviewer administered questionnaire. The students were asked whether they would undergo the same procedures in future as well as recommending the procedure to their friends. This lasted about 10–15 min  of the Makerere University College of Health Sciences and the Uganda National Council for Science and Technology (UNCST).Permission was also sought from the local governments of the study districts, school authorities and parents/guardians of the students and finally from the students who participated in the study. Written informed consent was obtained from the parents/guardians of the students who participated in the study and a written signed assent was obtained from the individual students. Privacy and confidentiality were strictly observed participation in the study was voluntary. Students who were found with helminthes infection were treated according to the Uganda National guidelines. In addition, the parents/guardians who participated in the focus group discussions gave informed consent to participate in the study.A total of 52 school students in grade 5 were approached to bring their parents to school; 45/52 (86.5 %) returned with their parents. The main reason for those that didn’t turn up was that they were attending to their gardens given the rainy season. Forty four 97.8 % students were enrolled while one girl was excluded due to menstruation.Their socio-demographic characteristics are shown in Table All students were willing to undergo the procedure again if necessary, and would recommend other students for the procedures. This gave acceptability for self-collected introital swab and self-collected stool sample of 100 %. Of the 44 students, 38 (88.4 %) were willing to provide a blood sample in future. Those who were not willing to participate gave pain during blood draw as the reason.The 12 participants included parents with an age range of 27–45 years, all Christians and of the same local language and diploma as the highest education level. Three major themes emerged with relevance to acceptability of study procedures: (1) Fear- of imagined process, consequences of the procedures and other undisclosed possible use of sample; (2) favorable opinion of the stool exam; (3) willingness to support vaccination programs and see them succeed.‘Eh, how can my little girl provide all that blood, won’t this cause some of our children to collapse?’ (Mother of 11 year old girl).The parents/guardians were concerned about the effect of blood draws on their daughters’ health and this feeling was shared by many of them. They thought that the 5 mls of blood collected from the students was too much and that it might lead to collapse. None of them knew how very little 5 mls was compared to the possible over 3000 ml which each student could have. With this clarity, this fear was dispelled.Um, us the old women we go to Ibanda hospital and they put an instrument under…..too big for these small girls….you see they have not known these things of adults…hu ….I didn’t know how you people were going to do this I was wondering how this can happen……….after your explanation and what you have showed us they will use………..the little stick……outside only….eh…we are now happy that it will not be the same as for us’ (Mother of 13 year old girl).The Program for Appropriate Technology in Health had set up cervical cancer screening centers and these women had the experience of cervical cancer screening which they had initially imagined would be the same procedure to be employed by the study. Though this fear was expressed here, these parents had already become comfortable with the procedure as it had earlier been demonstrated and they hoped it won’t change during the proposed study.‘Eh …eh….you people are just telling us other things for the blood…are you not going to use our childrens’ blood for other test like HIV ……um………..and others….we know some people want to study many things on Africans ………..’ (Father of 14 year old).‘Even if they study other things it is for our good…..our government protects us …um it is ok.’ (Father of 11 year old).There was some suspicion that the blood collected would be used to test the students HIV status and may be other diseases. However, some of them held other views on this;The research team clarified on some aspects of ethics on research and they were reassured that they are protected by the principals of research ethics. This fear too was dispelled.Eh …we are very happy about the stool exam………..you see our children can get treatment now if they are found with the worms…..that is very good……….. Thank you. (Mother of 12 year old).“We were a bit uncomfortable that you were just taking our girls’ blood and not sure of the motives, but when we saw you checking stool as well, we are now sure you are thoroughly checking our girls, which is good”. (Father of 15 year old).All the parents were happy for their children to undergo the stool collection procedure and examination and expressed no problem with it many of them saying it was good for detection of worms.We know vaccination has prevented diseases and we are happy….. we know our children will be well, but what about the results of the study’. (Father of 12 year old student).‘‘Um……. we see that our girls will be alright ….. when you come and explain everything to the parents and they understand……..our children can go ahead and participate in the study. (Mother of 14 year old).Majority of the parents were happy with the vaccination programs citing eradication of diseases like measles and polio. However many of them expressed need to know the results of the study for this vaccine that was given to their children.This view was echoed by majority of the parents and all of them expressed willingness to have their daughters participate in the future study.Pilot studies are a crucial element of a good study design and can provide valuable insights into the design of the main study. Reasons for conducting them may include among others developing and testing adequacy of research instruments, assessing the feasibility of the main study in terms of recruitment approach, logistical issues (finances and staff), sample collection methods as well as training needs for the research team . The genTherefore, we conducted the pilot study to mainly assess the acceptability of the procedures which were to be employed in the main study . In addition, during the conduct of the pilot study, valuable lessons were learnt which helped in the overall design of the main study.There was total acceptability of self-collected introital swabs and self-collected stool samples. However, six students did not accept to have blood drawn from them because of fear of pain. The first two procedures  were perceived to be painless while blood draw causes some transient pain. Despite the pain, a higher number would still undergo the procedure again. It is likely that this could improve even more if proper education and counseling are done on the necessity for the blood draw. The parents of the students expressed their fears about the procedures. They had these fears before they had the full explanations and demonstrations on how the procedures were to be done as well as the actual reason for the blood draw. After the demonstrations and explanations on the rationale of the exercise, the parents were able to understand the need for a study that will follow up the students to assess effectiveness of a vaccine that is hoped to help prevent cervical cancer a disease some of them had known about.Stool exam was very well accepted as the parents quickly understood a direct benefit of having stool examination. The strength of these findings lies in the exit interviews and focus group discussions that were conducted so as to measure acceptability in this sample of students and their parents. Unlike in another study , these iDespite the high acceptability, a small number of students may still refuse to undergo some of the procedures as evidenced in this study. Likewise, some parents may refuse to consent for their students. However, continuous education and sensitization to increase knowledge of benefits from HPV vaccine studies may enhance willingness to participate as evidence concerning hepatitis vaccine acceptability has showed .HPV DNA samples may be clinician collected or self-collected . The selOn average, the students in this study were older than their counterparts in the same class in urban setting. This trend is common in Uganda where children in rural areas tend to start school later than their counterparts in the urban areas. On the other hand the rural students tend to start sexual activity earlier than urban students , 19. ThiThe study had limitations. In our study, all the students were from two rural schools and were Christians. They were all from the same tribal region of Uganda. Given the tribal, cultural and religious diversity of Ugandans, the findings might not be generalisable to the rest of the Ugandan population. This is however from just a statistical view. We the researchers know that the study findings are more likely to apply to the rest of the Ugandan adolescent population since the fears that were expressed were not cultural or religious but physical for example pain.However, despite some of these lessons, very useful lessons were learnt. The process of approach to the school administration, mobilization of the parents for consent at the schools was refined for the main study. Finding no evidence of DNA on some of the introital swabs led to the change from having the students collect the samples unsupervised to having supervised collection while maintaining privacy. The distance from the field to the Laboratory that was to finally store the sample before shipping was too far (300 kms) for daily deliveries of the samples. So after this pilot, we were able to identify a laboratory about 80 km away (longest distance). In this laboratory, we would be able to take samples daily for centrifuging and storage at −80° centigrade. We were also able to find ways of safely handling stool samples without contaminating the school compound.Proposed study procedures to assess the effectiveness of the bivalent HPV vaccines were highly acceptable to both parents and their daughters. Lessons learned from the pilot included collection of the introital swab under supervision, all helped to inform the design of the final study.A follow up strategy to continue monitoring vaccine immunogenicity and effectiveness is therefore feasible in our setting and particularly in this group of young students.