To evaluate whether a full-coverage fetal-maternal scanner can noninvasively monitor ongoing electrophysiological activity of maternal and fetal organs.A simulation study was carried out for a scanner with an array of magnetic field sensors placed all around the torso from the chest to the hip within a horizontal magnetic shielding enclosure. The magnetic fields from internal organs and an external noise source were computed for a pregnant woman with a 35-week old fetus. Signal processing methods were used to reject the external and internal interferences, to visualize uterine activity, and to detect activity of fetal heart and brain.External interference was reduced by a factor of 1000, sufficient for detecting signals from internal organs when combined with passive and active shielding. The scanner rejects internal interferences better than partial-coverage arrays. It can be used to estimate currents around the uterus. It clearly detects spontaneous activity from the fetal heart and brain without averaging and weaker evoked brain activity at all fetal head positions after averaging.The simulated device will be able to monitor the ongoing activity of the fetal and maternal organs.This type of scanner may become a novel tool in fetal medicine. Magnetic Resonance Imaging (MRI) and ultrasound are useful for anatomical imaging of the maternal and fetal organs . UltrasoElectrical potential measurement techniques can be used to monitor the activity of maternal heart and other organs. The contractions of the uterus can be measured mechanically  can be monitored noninvasively on the maternal abdominal surface . The QRSvernix caseosa  we have developed recently . For the2This section describes our method for constructing the realistic torso model and several types of sensor array used in our simulation study. We present evaluation of an eventual FM scanner with a full-coverage sensor array wrapped around the torso of a pregnant woman to help readers understand the methods we evaluated for rejecting the interference from external noise sources and internal organs and how we determined the anticipated performance level of a full-coverage sensor array.2.1We constructed a realistic model of the torso of a pregnant woman carrying a fetus of 35 week GA based on the segmented anatomical data provided by FEMONUM repository  Fig. 1)Fig. 1). 2.2We computed the magnetic fields produced by external noise sources and different internal organs for two different types of sensor array. 2.3The initial design of our FM scanner is shown in Unlike the SQUID sensors based on superconductivity, the OPMs operate at room temperature, eliminating the need for handling of a cryogen, thus making the instrument potentially more widely useful. In the actual array, the sensors will be placed in light-weight, flexible belts, separated by about 5 cm from each other. Each belt conforms to the shape and size of the torso of any pregnant woman, unlike the rigid, fixed-shape arrays in the existing biomagnetometers. This flexible array guarantees that the sensors are all placed at the closest possible distance of 5 mm above the skin, thereby providing the maximum possible SNR for these sensors. In actual testing, the mother would lie on a set of 8 belts on the bed. The belts are flexible and easily conform to the shape of the torso. Once the mother is on the bed, the rest of each belt is placed over the torso. Each OPM probe is very light and does not cause discomfort to the mother. Once the sensors are in place, the bed slides into the bore of the magnetic shield.The shield will be made of two or three layers of hypermalloy metallic cylinders, combined with an external degaussing coil array and an internal active shielding coil array. The passive shielding creates an effectively “zero-field environment (<10 nT at DC and above up to about 100 Hz) for the zero-field OPMs to operate fully. The internal active shielding can be carried out by the low-sensitivity earth field OPMs  that can reduce the field further by a factor of about 1000 or to about 10 pT or less. This then brings the zero-field, high-sensitivity OPMs to operate within its dynamic range down to about 10 fT/√Hz.As mentioned below, an additional noise cancellation software technique, based on SSP, can be used to reduce this magnetic field to levels sufficient for measuring the biomagnetic signals from the maternal and fetal organs. The detection cell at the bottom of each OPM probe senses the magnetic field over the abdomen with a sensitivity of 5–15 fT/√Hz comparable to that of SQUIDs . The senCross-talk is a phenomenon in which the magnetic field applied to each OPM probe for reduction of the static field and modulation of the OPM cell influences the signal sensed by the adjacent probes. In the present study we have assumed that there is no cross talk. We expect this assumption to be fairly accurate since the separation between the probes is approximately 5 cm. The cross-talk for actual OPMs probes fabricated by QuSpin is <1.6% for this geometry and their sensors .2.4−4 Tesla. The fluctuation of the ambient field is normally about ±1 μT, for example in a room in the main building of our Boston Children’s Hospital. This ambient magnetic field can be reduced by a magnetic shielding enclosure such as the one shown in The magnetic noise from external sources is a major factor deteriorating the SNR. The external magnetic field can be very strong compared to magnetic fields from internal organs. The DC field of the Earth is about 0.5 × 10Rejection of external interference is thus a major problem for operating an FM scanner. We evaluated how well this type of interference can be eliminated by a combination of a whole-body coverage and a noise cancellation software technique. An external magnetic noise source was simulated by a cart moving longitudinally on one side of the mother at a velocity of 1 m/s, 3 m away from the central longitudinal axis of the sensor array. A magnetic noise source placed on the cart produced a temporal waveform of 10 s in duration (see www.martinos.org/mne) developed by one of us (Hämäläinen) for MEG/EEG research. We hypothesized that the SSP can provide a significant noise rejection that is sufficient for online monitoring of the signals from the fetal organs when the field is measured with a full-coverage sensor array. The results shown below fully confirm this hypothesis.To reject the external magnetic noise, we used the signal space projection (SSP) method . SSP has2.5We also studied how our sensor array can remove contaminations from various internal noise sources. When one is interested in measuring the activity of the fetal heart or brain, the signal from this target organ is contaminated by the magnetic field from the internal organs of the mother that are nearby (stomach and intestines) or that surround these fetal organs . We evaluated how well the full-coverage array can reject the noise from internal organs in comparison to various partial-coverage arrays. We placed 24 current dipoles inside the pregnant torso model by arranging two layers of 12 dipoles inside the body  and the full-coverage array (16 × 8 sensors). The outer surface of the myometrium in the FEM model with 873 nodes was defined as the source space. The activity was set up in a patch of the source space on the anterior side and in another patch on the posterior side of the uterus , top row2.7To evaluate the capabilities of the FM scanner for detecting the signals from internal organs, we modeled the activity in each target organ as an equivalent current dipole (ECD) source with a physiologically realistic amplitude and waveform. The source waveforms are based on the work of others. For the uterus, we used the data from the EHG database  with a cFetal heart - The detectability of electrical activity of the fetal heart was evaluated by first computing the magnetic fields produced by an external noise source, the uterus, the fetal heart and the fetal brain at the sensor locations of the full-coverage FM scanner and then by extracting the signal from the fetal heart in the presence of these “noise” sources. The magnetic field from the external noise source was calculated under the same condition as mentioned in Method section 4, except for the time course of the noise, which was a tapered 15 Hz sinusoid. The uterine dipoles were placed at five locations around the cervix of uterus. A single ECD was placed in the middle of the fetal heart and another dipole in the fetal brain. The magnetic field from the fetal heart was extracted from the mixture of the magnetic fields using a beamformer. In this method, data from all magnetic field sensors are combined to focus on the site of interest while suppressing interference from other potentially active sites. We used the linearly constrained minimum variance spatial filtering (LCMV) beamformer  - The detectability of electrical activity of the fetal brain was evaluated by following the same procedure used for extracting the magnetic field from the fetal heart. The same mixture of the magnetic fields from the different external and internal sources for the fetal heart was used for this analysis. The magnetic field from the fetal brain was extracted using the same beamformer as for the fetal heart. This procedure evaluated the detectability of spontaneous signals of the fetal brain.Fetal brain  - Cortical activity that can be evoked by external stimulations such as sound, light, or even linguistic stimuli is much weaker than spontaneous brain signals. The amplitudes are 10–100 fTrms as compared to 100–500 fTrms for spontaneous brain activity at the abdomen  and orientation (θ and ϕ) of the noise source relative to the signal dipole and on the coverage angle (Ω) of the sensor array. When the noise dipole is shallow , the subWhen the noise dipole is deeper and/or lateral, ϖ becomes dependent heavily on Ω as well as on θ and ϕ. 3.33.4p-p for the QRS complex and ∼1 pTp-p for the brain. Thus, the relatively weak fetal signals are extracted in the presence interference 10–50× stronger.3.5The capability for detecting cortical evoked activity was evaluated for sensor arrays varying in angular coverage as a function of depth of the fetal brain source. The rms strength of the signal from the dipolar fetal brain source was calculated as a function of the dipole depth without any internal noise source and in the presence of these noise sources. These results demonstrate that the full-coverage sensor array is superior to the partial-coverage sensor arrays. The signal level for the full-coverage array is 1–2× the noise level expected for the OPM instrument  even when the brain is deep (∼5–10 cm from the anterior or posterior side). The SNR can be, therefore, >10:1 if 100 evoked responses are averaged. Evoked cortical responses can be thus measured with a SNR of close to 10:1 in ∼3 min with a presentation rate of one stimulus every 2 s. This indicates that it should be possible to study cortical activity elicited by external stimulations within a reasonable period of time using a full-coverage FM scanner.4This study evaluated the possibility of noninvasively measuring ongoing electrophysiological activity of the uterus and fetal organs with a biomagnetic technique. Overall, we showed that it should be possible to monitor the activity online in real time using a novel type of biomagnetic instrument that provides a full coverage for measuring the magnetic field from the chest to the hip area of a pregnant mother. The online monitoring capability would provide an important new power in analysis and diagnosis important for maternal and fetal health care since the results could be used for immediate feedback in optimizing the monitoring procedure or interventions. The intervals between the QRS’s in fetal ECG can be used to estimate the instantaneous heart rate, which is useful for monitoring cardiac arrhythmia . It is p4.1One of the major problems in detecting the magnetic fields from internal organs of a pregnant woman is rejection of external magnetic interferences. Conventionally, this is accomplished by measuring the magnetic field inside a magnetically shielded room (MSR) . An MSR The use of a large MSR is costly and has inhibited the popular use of biomagnetic methods for clinical applications. In the present study, we considered an alternative, much more economical method of magnetic shielding, using a cylindrical shield that can fit into an enclosure that looks like a small MRI scanner. A 3-layer mumetal cylindrical shield has been used for an atomic magnetometer system . The FM 4.2In addition to rejecting the external interference, the magnetic field from various internal organs must be separated in order to detect the signal from an organ of interest. We have shown that our full-coverage sensor array design is superior to partial-coverage sensor arrays with a varying degree of coverage around the torso. The existing FM scanners such as SARA provide a coverage of about 110° or less around the torso . As was 4.3The activity of the uterus is important for understanding the preterm and term labor. The physiology of uterine contraction has been studied in animal models . The mecWe have shown that currents in the uterine wall at the source level can be visualized. The full coverage array could visualize the activity on the anterior and posterior sides of the uterus, whereas a partial coverage array could visualize the activity only on the anterior surface, but not on the posterior surface. This result suggests that the full-coverage FM scanner may be used to visualize the activity in the entire uterus. We still do not know the sensitivity of this technique. However, it is worthwhile exploring the possibility of detecting the myogenic activity during the relative quiescent period between contractions for understanding the development of synchronized activity preceding the onset of contractions and labor or even during the menstruation cycles. If the activity can be detected clearly during the quiescent period, one could try to visualize the initiation site and the propagation pattern.The measurements of the uterine activity can be combined with mathematical models of the electrophysiology of the uterus being developed by several groups  for incr4.4Our simulation study indicates that it might become possible to detect the fetal MCG online. The fetal MCG signals can be detected with the existing FM scanners . HoweverEchocardiography cannot detect the electrical activity during the mechanically silent period such as the ventricular repolarization phase . Neither4.5In addition to detection of fetal heart activity, our simulation study indicates that it might become practical to detect the ongoing spontaneous activity of the fetal brain in utero. This capability, if validated, would represent a major advance in obstetrics and fetal medicine . Our resIt might also become possible to detect evoked cortical activity from the fetal brain with a relatively small number of averages over a wide range of head positions. The detection of evoked brain activity in the fetus is a big challenge today . It may 5Based on the performance seen in this simulation study, we predict that it will become possible to monitor the ongoing electrical activity of the uterus and fetal brain and heart in real time using a full-coverage FM scanner. The full-coverage array is useful for reducing the magnetic interference from external noise sources to a level close to the instrumentation noise level. It is also useful for rejecting the magnetic interference from internal organs throughout the torso of the mother to clearly detect the electrophysiological activity of the internal organs of interest. We anticipate this approach could become very useful as a new clinical modality in clinical neurophysiology and fetal and maternal medicine.


An effective and efficient notifiable diseases surveillance system (NDSS) is essential for a rapid response to disease outbreaks, and the identification of priority diseases that may cause national, regional or public health emergencies of international concern (PHEICs). Regular assessments of country-based surveillance system are needed to enable countries to respond to outbreaks before they become PHEICs. As part of a broader evaluation of the NDSS in South Africa, the aim of the study was to determine the perceptions of key stakeholders on the national NDSS attributes of acceptability, flexibility, simplicity, timeliness and usefulness.During 2015, we conducted a nationally representative cross-sectional survey of communicable diseases coordinators and surveillance officers, as well as members of NDSS committees. Individuals with less than 1 year experience of the NDSS were excluded. Consenting participants completed a self-administered questionnaire. The questionnaire elicited information on demographic information and perceptions of the NDSS attributes. Data were analysed using descriptive statistics and the unconditional logistic regression model.p = 0.041); those in disease detection were less likely to perceive it as timely  and those participating in National Outbreak Response Team were less likely to perceive it as useful .Most stakeholders interviewed  were involved in disease control and response. The median number of years of experience with the NDSS was 11 years (inter-quartile range (IQR): 5 to 20 years). Regarding the NDSS attributes, 25 % of the stakeholders perceived the system to be acceptable, 51 % to be flexible, 45 % to be timely, 61 % to be useful, and 74 % to be simple. Health management stakeholders perceived the system to be more useful and timely compared to the other stakeholders. Those with more years of experience were less likely to perceive the NDSS system as acceptable  contains supplementary material, which is available to authorized users. Notifiable disease surveillance systems (NDSS) in the 21st century should be capable of rapid identification of priority diseases that cause national, regional or public health emergencies of international concern (PHEIC). An effective and efficient NDSS could enhance the ability of a country to respond rapidly to outbreaks before they become PHEICs. Regular evaluations of the surveillance system are needed to ensure this capability, as well as relevance and usage by the key stakeholders. Furthermore, the PHEICs caused by the Ebola Virus Disease (EVD) outbreak from 2014 to 2016 [At a global level, an independent panel appointed by the World Health Organization (WHO) in response to the EVD outbreak found that countries failed to develop International Health Regulations (IHR) surveillance core capacities . The panIn high-income countries in Europe  and AustThe NDSS in South Africa has been in existence since the late 1970s. The NDSS in South Africa is a paper-based system that tracks 33 medical conditions. In terms of existing legislation, all health care providers are obliged to notify these 33 conditions to their local authority, which in turn reports it to the district, district to province, and province to the NDOH  and all nine provincial health departments, as well as members of the National Surveillance Forum, the South African Malaria Elimination Committee, the South African Expanded Programme on Immunisations Committee and the National and Provincial Outbreak Response Teams (NORT and PORT respectively), to participate in a cross-sectional survey. As experience is an important determinant of the perspectives of the stakeholders, we excluded those not working in a health related field and those with less than 1 year experience of the NDSS from the study.We developed an electronic semi-structured questionnaire  to 7 (strongly agree). The questions were phrased in a manner that attempted to minimise an unreflective response by participants, for instance questions requiring a positive response were alternated with questions requiring negative responses so that respondents would not be tempted to continue answering all the questions using the same response. Cronbach’s alpha coefficients were calculated to determine reliability and coherence between items and ranged from 0.82 to 0.97, indicating high reliability and inter-item correlation.We piloted the questionnaire prior to implementation, and no changes were deemed necessary. The questionnaire was in English as this is the official language used for business communication in South Africa. On 7 April 2015, we electronically sent invitations for participation in the survey to all identified key stakeholders via REDCap. The first page of the questionnaire consisted of an information sheet and we asked participants to consent before completing the survey electronically. Those not consenting were allowed to opt out. We sent four reminders to participants who did not respond after 2 weeks and we closed the survey on 31 May 2015, after 54 days from the enrolment date.We captured data entered by participants in REDCap and exported the data into STATA® 14 for cleaning and analysis. We computed frequency and summary tables to describe participants’ age, position, experience, training and roles on committees. We summarized categorical variables in tables showing frequency and percentage of each category. We also summarized numerical/measured variables using means (standard deviations) or medians (ranges) depending on whether they could be assumed to be normally distributed or skewed.p-values. P-values of less than 0.05 were considered to be statistically significant.We analysed responses from 7-point Likert scale attribute questions by describing the frequency distribution for each point on the scale. In order to simplify the interpretation of the results, we then categorized the responses to each question on NDSS attributes as agree or disagree. We excluded the ‘neither agree nor disagree’ response in the analysis. We then computed the percentage of respondents who agreed with a particular attribute. We conducted a sensitivity analysis using two additional scenarios: in ‘scenario 2’, we combined the responses of participants who indicated ‘neither agree nor disagree’ with the responses of those participants who indicated ‘agree’ to the questions; in ‘scenario 3’, we combined the responses of participants who indicated ‘neither agree nor disagree’ with the responses of those participants who indicated ‘disagree’ to the questions. In the final stage of the analysis, we determined whether participants’ age, experience, training and roles with regards to the NDSS were associated with each of the attributes using the unconditional logistic regression model. The outcome variable was whether the participant agreed with the attribute or not. We calculated odds ratios (OR), 95 % confidence intervals (95 % CI) and n = 11), worked in a non-health related field (n = 9), and with less than 1 year experience with the NDSS (n = 7), the final sample size was 114. The median age of key stakeholders was 49 years, ranging from 26 to 69 years. The median number of years of experience in the NDSS was 11 years (inter-quartile range (IQR): 5 to 20 years). The median duration of NDSS training was 2 weeks. Most of the key stakeholders who participated in NDSS committees, participated in the NORT (43 %). ; disease detection ; health management ; and others (undetermined responsibility in the NDSS). Most key stakeholders were involved in disease control and response (53 %), and these stakeholders were younger, with a median age of 41 years, compared to 55 years in the health management group.The proportion of participants who strongly agreed with any of the attributes was small, with the highest value of 7.5 % for simplicity. The proportion of participants who agreed was slightly higher at around 10 % except for timeliness. An even higher proportion slightly agreed, at around 30 %, with the exception of acceptability. The proportion of participants who neither agreed nor disagreed was also around 30 % for all attributes with the exception of flexibility. The proportion of those who slightly disagree were higher in all attributes with the exception of simplicity. The proportion of those who either disagreed or strongly disagreed was higher for acceptability and flexibility, but negligible for the other attributes. The perceptions of participants for each attribute are shown in Fig. After categorizing the responses into agree/disagree and excluding those that neither agreed or disagreed, we found that 25 % of the stakeholders perceived the NDSS to be acceptable, 51 % to be flexible, 74 % to be simple, 45 % to be timely,, and 61 % to be useful. A higher percentage of participants in Health Management perceived the system to be simple, useful and timely. Participants from the ‘Other’ category that includes those with an undetermined responsibility in the NDSS, perceived the system to be more flexible. Similarly, stakeholders participating in PORT perceived the system to be more simple and useful, compared to those in other NDSS committees. . Participants working in disease detection were less likely to perceive the NDSS as timely , while those participating in NORT were less likely to perceive the NDSS as useful . However, there was no association between years of experience or respondents’ place of employment and the stakeholder perceptions on the NDSS attributes of flexibility and simplicity.  and those trained in the NDSS perceived the system to be simpler .In Scenario 2, participants younger than 35 years were more likely to perceive the NDSS as acceptable  . CompariThe usefulness score of 61 % was also lower than the one obtained in the Australian study that found that 94 % of participants reported reading NDSS reports and 85 % reported using the data . This maWhen considering perceptions in terms of responsibility in the system, those stakeholders involved at an operational level (disease detection and response) scored the usefulness, simplicity and timeliness of the NDSS lower than those in health management. The perceptions of health management may be an overestimation because they may have regarded the NDSS evaluation as a reflection of their own performance. Hence the scores may reflect social desirability bias. In terms of participation in NDSS committees, those participating in the provincial committees, PORT, scored the simplicity and usefulness of the NDSS higher than those in national committees. As is the case with health management, social desirability bias may again have played a role here as provinces are mainly responsible for the NDSS implementation.Results from the logistic regression analysis showed that the stakeholders in disease detection and national committees, NORT, involved with oversight of the system, as well as those with more years of experience with the system were less likely to perceive the NDSS as acceptable, timely or useful. This may represent a true reflection of the level of functioning of the system as the surveillance officers, epidemiologists, pathologists, communicable disease coordinators and public health officials are involved with the NDSS on a daily basis in an operational and monitoring capacity – the acceptability, timeliness and usefulness of the NDSS have direct application to their daily work. On the other hand, the perceptions of oversight structures may be a reflection of their distance from the operational functioning of the NDSS.Although the result of the sensitivity analysis in Scenario 2 showed an increase in timeliness to 77 %, this would not alter our conclusion as it still fall below a level that could be regarded as satisfactory for the effective function of the NDSS. However, in Scenario 2, a score of 92 % for simplicity is very good, and implies that no intervention is needed to improve the simplicity of the NDSS.With regard to factors found to be associated with the perceptions in Scenario 2, the finding that training was associated with simplicity imply that addressing training needs would increase the understanding of the processes and forms used in the system. The finding that participants younger than 35 years found the system more acceptable, should inform additional training and feedback that should be used to revitalise the NDSS. Training and feedback influence the value that stakeholders at the coalface attach to the system and affect their willingness to participate in it. Without the participation of stakeholders at all levels the NDSS cannot fulfil its purpose.The main limitation of this study was that it was based on the perceptions of individuals and not on the actual records of notifications, which is the focus of another study. Perceptions are influenced by social desirability bias among stakeholders surveyed. Although every attempt was made to include all the relevant key stakeholders at national and provincial levels, some stakeholders may not have been identified. The findings of this study will be validated through further studies on the actual records of notifications. Another limitation was the dearth of national or provincial studies on the South African NDSS to compare the research findings with. The study findings suggest the need for reforms of the South African NDSS, with particular focus on the attributes of acceptability, flexibility, timeliness and usefulness. We recommend the phased introduction of an electronic system that includes the use of mobile telephone technology to address the current perceived weaknesses in the NDSS attributes. This is because the latter has a high penetration in the South African population. In 2015 there have been some encouraging developments with regard to malaria surveillance  that couAt a global level, the findings of this study indicate a need for objective evaluations in support of annual IHR country submissions to the WHO. We recommend that objective assessments, using the baseline data provided in this study, be conducted every three to 5 years. This should be complemented with comparative studies of notification versus laboratory surveillance to provide a comprehensive evaluation of the NDSS in South Africa.This study found that the majority of key stakeholders scored the NDSS in South Africa low on the attributes of acceptability, flexibility, and usefulness. Factors found to be associated with key stakeholders perceptions were years of experience, training in the NDSS, age less than 35 years, participation in disease detection and NORT. The overall poor perceptions of NDSS stakeholders on the system attributes are a cause for concern. The study findings should inform the revitalisation and reform of the NDSS in South Africa to address stakeholder concerns. This should be done in consultation and in partnership with the stakeholders.


Miscarriages are a common pregnancy complication affecting about 10–15% of pregnancies. Miscarriages may be associated with a myriad of psychiatric morbidity at various timelines after the event. Depression has been shown to affect about 10–20% of all women following a miscarriage. However, no data exists in the local setting informing on the prevalence of post-miscarriage depression. We set out to determine the prevalence of positive depression screen among women who have experienced a miscarriage at the Aga Khan University hospital, Nairobi.The study was cross-sectional in design. Patients who had a miscarriage were recruited at the post-miscarriage clinic review at the gynecology clinics at Aga Khan University Hospital, Nairobi. The Edinburgh postpartum depression scale was used to screen for depression in the patients. Prevalence was calculated from the percentage of patients achieving the cut –off score of 13 over the total number of patients.A total of 182 patients were recruited for the study. The prevalence of positive depression screen was 34.1% since 62 of the 182 patients had a positive depression screen. Moreover, of the patients who had a positive depression screen, 21(33.1%) had thoughts of self-harm.A positive depression screen is present in 34.1% of women in our population two weeks after a miscarriage. Thoughts of self-harm are present in about a third of these women (33.1%) hence pointing out the importance of screening these women using the EPDS after a miscarriage.The online version of this article (10.1186/s12888-018-1619-9) contains supplementary material, which is available to authorized users. A miscarriage is the premature loss of a fetus prior to viability. This may have different definitions depending on a regions’ definition of the cusp of viability but the World Health Organization (WHO) defines it as the premature loss of a fetus up to 23 weeks of pregnancy and weighing up to 500 g . MiscarrWhether they are spontaneous or induced miscarriages have a significant implication in psychiatric morbidity of the involved women , 9. HoweDepression in women who have had a miscarriage occurs at various timelines after the miscarriage episode . StartinThere is paucity of local literature with regards to incidence of depression after a miscarriage and the factors influencing its occurrence with no studies published with regards to its prevalence in the African population. Henceforth, we set out to determine the prevalence of depressive illness in patients after a miscarriage at a private tertiary teaching hospital in Kenya.To determine the prevalence of positive depression screen for women who have experienced a miscarriage at the Aga Khan University Hospital Nairobi.The study was a cross-sectional study where we examined both the exposure to a miscarriage to the outcome of depression at the same time.The study was conducted at the Aga Khan University hospital Nairobi . Participants were recruited from the Gynecology Clinics, which run daily, at the clinic review after a miscarriage. A miscarriage was defined as a pregnancy loss occurring at or before 23 weeks of a pregnancy or the miscarriage of a fetus of less than 500 g. Participants had some sort of treatment of the miscarriage including expectant, medical or surgical management. The clinic review was usually scheduled 2 weeks after the miscarriage but had a range of between one and 3 weeks. We further explore the choice of the study participants in the discussion.We included women in the reproductive age group (15–49 years) who had experienced a miscarriage which were either spontaneous or induced. We excluded other forms of early pregnancy losses like women with a diagnosed ectopic pregnancy in order to eliminate it compounding the analysis of the impact of the mode of treatment on prevalence of depression. Women with previously diagnosed depression were also excluded.Participants were required to sign consent to be included in the study after which two types of data were collected from the patient. A demographics tool and the Edinburgh Postnatal Depression scale (EPDS)  was admiThe study used two tools to collect information from the patients – a demographics tool and the EPDS.The demographics tool was created for the study which collected the patients file number, age and other associated factors that may impact on the occurrence of post-miscarriage depression. These factors included the patient’s age, educational background, gestation at miscarriage, marital status, planning of the pregnancy, social support, mode of treatment of the miscarriage, number of prior miscarriages, mode of conception and prior pregnancy outcome.Depression symptoms were measured using the Edinburgh Postnatal Depression Scale . P = Expected prevalence of Post miscarriage depression at AKUH, N. d = Precision around expected prevalence ±0.05. Substituting for the equation:The patients were selected by a consecutive sampling method.The prevalence of positive depression screen for women who have experienced a miscarriage was determined as a percentage of patients who screened positive from the total participants. Descriptive statistics for continuous variables, such as age and gestation age at the miscarriage, were done to describe the baseline characteristics of women in the screen – positive and screen – negative groups. The statistical package for the social sciences (SPSS) version 22 was used for data analysis. Data were represented in tables and graphs.Ethical approval was obtained from the Research and Ethics committee at the AKUH, N. Participants were recruited after obtaining written informed consent as per study protocol. Patients had the right to refuse or withdraw from the study at any point and this did not impact on the quality of care received subsequently. The study used alternative study numbers to maintain patient privacy and confidentiality. The data collection forms were safely kept in a locked cabinet to which only the primary investigator and the research assistant had access to. Patient who screened positive for post-miscarriage depression had an appointment booked for further evaluation and management by the psychiatrist, this however was at their own cost. Around 80% (50 of the 62) of women referred attended a psychiatrist follow up, the number included the women who had suicidal ideation and they were offered appropriate counselling and follow up.A total of 182 patients were recruited for the study. The patients were recruited from the outpatient gynecological clinics at the AKUH. No patients were excluded from this number since they all had their documentation in full.n = 159) with less having a primary level  or secondary level of education .The age of the patients recruited varied from as low as 17 years to the oldest being 45 years old. The mean age was 29.42 (SD = 5.6) years as shown in Table n = 41). A large percentage  of the patients were married with also a high percentage of the pregnancies being planned . A high proportion of these women with miscarriages had social support with 89.6% (n = 163) living with other individuals and this corresponded to the high percentage of them having another individual aware of their pregnancy . This information is also displayed in Table n = 124) of the women recruited had not experienced a previous miscarriage with about a quarter having experienced one prior miscarriage  and much less having had 2 or 3 prior miscarriages. Most women had conceived spontaneously  with 37.4% (n = 68) having had a live birth in their previous pregnancy  with a small percentage  requiring a combination of more than one mode of treatment  had thoughts of self-harm which were distributed as shown in Fig. 3.8% had Miscarriages are common especially in early pregnancy and with the growing concern about its mental health implications, it’s an area of growing interest in obstetrics and gynaecology. The present study set out to determine the prevalence of positive depression screen among women who have had a miscarriage.The present study recruited 182 women who had miscarriage and screened them after having had treatment for the miscarriage. The patients recruited had a mean age of 29.42 years with the youngest being 17 years and the oldest 45 years. More so, although it is known that miscarriages tend to increase with advancing age , most ofThe mode gestational age at miscarriage was 8 weeks. This is in keeping with previous studies in miscarriages as most are seen within the first trimester and tend to reduce with advancing age . This paMost of women recruited in this study had an advanced level of education with 87.4% having a college or university level education. This is in keeping with studies done in pregnant women from a similar population. Majority of the women recruited were married (81.3%) and more of their pregnancies were planned (72.5%). This again just points out to the social strata of most patients with a miscarriage in our setting [The prevalence of positive depression screen in post miscarriage women in our study was 34.1%. Sixty two of the 182 women had an EPDS score of 13 or more. This is the highest prevalence of positive depression screen after a miscarriage reported in recent literature. Previous studies reported a prevalence ranging from as low as 10% to as high as 28.7% , 15. Then = 21) of the women who screened positive for post miscarriage depression. Although it was noted that most of the women hardly ever had these thoughts, it is concerning that they are present in the setting of post miscarriage depression. No studies have been done in post miscarriage women assessing their thoughts of self-harm, however in postnatal women assessed with the EPDS the prevalence reported varies from around 4–20% [Thoughts of self-harm were observed in about a third  hence pointing out the importance of screening these women using the EPDS after a miscarriage. The prevalence documented in this study outlines the importance of screening of women after a miscarriage for depression, more so, with associated self-harm in a third of these women this further strengthens the argument for universal screening. With universal screening, earlier pick up of these women may reduce the subsequent well documented effects of depression and primarily offer better universal care after a miscarriage. Moreover, the role of universal counselling after a miscarriage and its impact on reduction of depression needs to be explored in the clinical setting.


A crucial point in statistical mechanics is the definition of the notion of thermal equilibrium, which can be given as the state that maximises the von Neumann entropy, under the validity of some constraints. Arguing that such a notion can never be experimentally probed, in this paper we propose a new notion of thermal equilibrium, focused on observables rather than on the full state of the quantum system. We characterise such notion of thermal equilibrium for an arbitrary observable via the maximisation of its Shannon entropy and we bring to light the thermal properties that it heralds. The relation with Gibbs ensembles is studied and understood. We apply such a notion of equilibrium to a closed quantum system and show that there is always a class of observables which exhibits thermal equilibrium properties and we give a recipe to explicitly construct them. Eventually, an intimate connection with the Eigenstate Thermalisation Hypothesis is brought to light. Jaynes principle123SvN = −Trρ logρ. Jaynes showed that the unique state that maximises SvN (compatibly with the prior information that we have on the system) is our best guess about the state of the system at the equilibrium. The outcomes of such procedure are the so-called Gibbs ensembles.To understand under which conditions thermodynamics emerges from the microscopic dynamics is the ultimate goal of statistical mechanics. However, despite the fact that the theory is more than 100 years old, we are still discussing its foundations and its regime of applicability. The ordinary way in which thermal equilibrium properties are obtained, in statistical mechanics, is through a complete characterisation of the thermal form of the state of the system. One way of deriving such form is by using de facto is not experimentally testable because it gives predictions about all possible observables of the system, even the ones which we are not able to measure. To overcome this issue, we propose a weaker notion of thermal equilibrium, specific for a given observable.In the following we argue that such a notion of thermal equilibrium, The issue is particularly relevant for the so-called “Pure states statistical mechanics”567891011121314151617182021222324SvN is a way of estimating the uncertainty that we have about which pure state the system inhabits. Unfortunately we know from quantum information theory that it does not address all kind of ignorance we have about the system. Indeed, it is not the entropy of an observable (though the state is observable); its conceptual meaning is not tied to something that we can measure.The starting point of Jaynes’ derivation of statistical mechanics is that ρG): the number of observables needed to probe all the density matrix elements is too big. In any experimentally reasonable situation we have access only to a few (sometimes just one or two) observables. It is therefore natural to imagine situations in which the outcomes of measurements are compatible with the assumption of thermal equilibrium, while the rest of the density matrix of the system is not.This issue is intimately related with the way we acquire information about a system, i.e. via measurements. The process of measuring an observable p(λj)} of an observable Despite that, we think that the fact that a distribution is compatible with its thermal counterpart will lead to the emergence of certain thermal properties, concerning the specific observable under scrutiny. Building our intuition on that, we propose a new notion of thermal equilibrium specific for a given observable, experimentally verifiable and which relies on a figure of merit that is not the von Neumann entropy. A good choice for such a figure of merit comes from quantum information theory and it is the Shannon entropy j is the projector onto the eigenspace defined by the eigenvalue λj. p(λj) ≡ Tr(ρΠj)Throughout the paper we will work under the assumption that the Hilbert space of the system has finite dimension and we will refer to the case in which the Hamiltonian of the system has no local conserved quantities, even though it is possible to address situations where there are several conserved quantities, like integrable quantum systems. We will also assume that the observable has a pure-point spectrum with the following spectral decomposition where We propose to define the notion of thermal equilibrium, for an arbitrary but fixed observable is at thermal equilibrium when its eigenvalues probability distribution p(λj) maximises the Shannon entropyunder arbitrary perturbations with conserved energy. We call an observable with such a probability distribution: thermal observable.p(λj) = peq(λj), there will be several quantum states ρ which give the same probability distribution for the eigenvalues λj. In this sense this is a weaker notion of equilibrium, with respect to the ordinary one.It is important to note that this notion characterises only the probability distribution at equilibrium and it does not uniquely identify an equilibrium state. Given the equilibrium distribution In the rest of the paper we study the main consequences of the proposed notion of observable-thermal-equilbrium: its physical meaning and the relation with Gibbs ensembles. The investigation will show that the proposed notion of equilibrium is able to address the emergence of thermalisation. This is our first result.Hamiltonian Unbiased Bases (HUBs) and, accordingly, we call an observable which is diagonal in one of these bases Hamiltonian Unbiased Observable (HUO). The existence and precise characterisation of observables which always thermalise in a closed quantum system is our second result. Furthermore, we investigate the relation between the notion of thermal observable and one of the main paradigms of pure states statistical mechanics: the Eigenstate Thermalisation Hypothesis (ETH)27282930313233343536Furthermore, we study the proposed notion of equilibrium in a closed quantum system and prove that there is a large class of bases of the Hilbert space which always exhibit thermal behaviour and we give an algorithm to explicitly construct them. We dub them In the conclusive section we summarise the results and discuss their relevance for some open questions.The request that the equilibrium distribution must be a maximum for T〉 = E0, where T is the Hamiltonian of the system. The Hamiltonian has the following spectral decomposition T = ∑αEαTα, where ρn are the respective projectors and qn its eigenvalues. To describe the state of the system we use the following convenient basis: j runs over different eigenvalues λj of s accounts for the fact that there might be degeneracies. We also make use of the projectors We assume that the only knowledge that we have on the system is the normalisation of the state and the mean value of the energy 〈E0 is always subject to uncertainty, which we call δE. In this sense, all the states δE, we note that it is usually assumed to be small on a macroscopic scale but still big enough to host a large number of eigenvalues of the Hamiltonian.It is worth to note that the knowledge of Exploiting Lagrange’s multipliers technique we obtain four sets of equations. Derivatives with respect to the multipliers enforce the validity of the constraints while the derivatives with respect to the overlaps give two independent set of equations. Using two linear combinations of them we obtain the following equilibrium equations (EEs):λE and λN are the Lagrange multipliers associated to where the overbar indicates complex conjugation. peq(λj) has to be be invariant under the unitary dynamics. Indeed, writing the time evolution equation for p(λj) we obtainThe first step is to understand the physical meaning of these equations. The first one  gives theq” stands for “after plugging in the EEs”.where the superscript “The second equation  fixes thThere is a linear contribution in the mean value of the energy, plus a “zero-point” term We now come to the issue of understanding if our proposal is compatible with Gibbs ensembles. First we note that the ordinary notion of thermal equilibrium is much more stringent than ours, being a complete characterisation of the state of the system. Thus, we need to find the condition under which our criterion gives the full state of the system. Since we are using a maximum-entropy principle, a plausible auxiliary condition is the maximisation of the smallest among all Shannon entropies. Such a request fully characterises the state of the system because the lowest Shannon entropy of the state is unique: it is the one in which the density matrix is diagonal. Indeed, using the Schur-concavity of the Shannon entropy and the Schur-Horn theoremwhere In the next section we will apply the proposed notion of thermal observable to the so-called “pure-states statistical mechanics”56789ETH, in its original formulation272829303132ω ≡ Eα − Eβ while δε is a smeared version of the Dirac delta distribution. Rαβ is a complex random variable with zero mean and unit variance. Furthermore, we remember that ETH by itself does not guarantee thermalisation, we need to impose that the initial state has a small dispersion in the energy eigenbasiswhere ρmc = ρmc is the microcanonical state defined by the condition on the average value of the energy TrρT ∈ I0.where From the conceptual point of view, the “small energy-dispersion assumption” is a key element of the emergence of thermal equilibrium but it has nothing to do with ETH which, by itself, is only the ansatz in 18α ∈ I0 means α: Eα ∈ I0.Before we continue we define the following short-hand notation: E, with respect to the average energy E0: E = 0. With such a choice, we are left with an Hamiltonian eigenstate and a constraint equation given by TrρH = Eα. We note that To study the relation with ETH we need to change perspective. The point of view that we are adopting is the following. One of the key-points behind the ETH is that, in many real cases, the expectation values computed onto the Hamiltonian eigenvectors can be very close to the thermal expectation values. Moreover, when one wants to argue that thermalisation in a closed quantum system arises because of ETH, a main assumption is that the initial pure state of the system With this assumption, the second equilibrium equation becomesp(λj) on both sides, the right-hand side does not depend on the label j. Hence, keeping in mind that xlogx → 0 for x → 0, the most general solution of this equation is a constant distribution with support on some subset (Eα) of the spectrum and zero on its complementary:After crossing where It has to be understood here that mutually unbiased bases (MUB)3940A similar relation has already been studied within the context of quantum information theory. Two bases of a N-dimensional Hilbert space of N qubits, there are 2N + 1 MUBs and we have an algorithm to explicitly find all of themSuch a concept is a generalisation, expressed in term of vector bases, of canonically conjugated operators. In other words, each vector of HT has a small value, because the profile of the distribution will be peaked around a certain value. For such a reason By assumption, the pure state in Eq. (??) has an energy distribution Moreover, it can be proven that between any pair of MUB, like the Hamiltonian eigenbasis and an HUB, there exists the following entropic uncertainty relation, involving their Shannon entropiesPutting together This in turn implies that the distribution of all the HUO will be approximately the same as the one computed on the microcanonical state.For such a reason, we now study the properties of a HUO:In order to investigate the relation with ETH we need to study the matrix elements of a HUO in the energy basis:with This is the first part of our third result and as it is, it can already be used to explain the emergence of thermalisation in a closed quantum system. In refs cα ≡ 〈ψ0|Eα〉 and δE, there will be a huge number of eigenstates within the range Eα ∈ I0. To conclude, given a HUB it is always possible to obtain a HUO which satisfies the finite-range assumption. We can therefore apply Reimann’s theorem to HUOs.where It is important to note that Reimann’s theorem explains equilibration around the DE but this does not necessarily entail thermalisation. The DE still retains information about the initial state while thermalisation is defined  by the independence on the initial state. This is the point where our result is able to take a step forward and explain the emergence of thermal equilibrium in the HUOs. We can use π, π], with a constant probability distribution.In order to prove that a HUO satisfies ETH we need to study also its off-diagonal matrix elements. By using λj and this will make the value of the off-diagonal matrix elements severely smaller than the value of the diagonal ones:There are different ways in which this result can be used. The general argument is the following: in The randomness of the coefficients involved in the evaluation of the off-diagonal matrix elements has been recently proposed as the basic mechanism to explain the In order to understand how this works in practice we need to say something specific about the eigenvalues. We highlight two important cases in which our result is helpful: an observable which is highly degenerate and an observable whose eigenvalues distribution is not correlated with the phases Assuming that σ2 and In which λj}j,s and the phases If the eigenvalues distributions {Where we used the fact that the two sequences are uncorrelated to approximate the sum as the product of two sums and in the second identity we used the fact that I0. It is straightforward to see that the same results hold when the state is the microcanonical state ρmc involved in ρT ∈ I0.These results follows from the study of the equilibrium equations, under the assumption that the state is an Hamiltonian eigenstate thermal observable when its eigenvalues probability distribution maximises its Shannon entropy We proposed a new notion of thermal equilibrium for an observable In the second part of the paper we studied the emergence of thermal observables in a closed quantum system and especially their relation with the ETH. Using maximisation of Using this characterisation, we studied the matrix elements of an HUO in the Hamiltonian eigenbasis. The study of the diagonal matrix elements reveals that they always satisfy ETH. This has been used to prove thermalisation of the average value of HUOs, in connection with Reimann’s theorem about equilibration of observables. The study of the off-diagonal matrix elements revealed that their value is exponentially suppressed, in the dimension of the Hilbert space. This completes the proof that HUOs satisfy the ETH. The proven relation between ETH and HUOs is our third and last result. The relevance of this result for the pure-states statical mechanics is related to the two main objections usually raised against ETH: the lack of predictive power for what concern both which observables satisfy ETH and how long it should take them to reach thermal equilibrium. The proposed notion of thermal equilibrium is therefore revealing its predictive power since it gives us a way of finding observables which always satisfy ETH, in a closed quantum system.We would like to conclude by putting this set of results in a more general perspective. ETH is one of the main paradigms to justify the applicability of statistical mechanics to closed many-body quantum systems. However, it is just a working hypothesis, it is not derived from a conceptually clear theoretical framework. For such a reason, one of the major open issues is its lack of predictability. Despite that, there has been a huge effort to investigate whether the ETH can be invoked to explain thermalisation in concrete Hamiltonian models4344454647484950515253545556Further investigation in this direction is certainly needed, but we would to suggest a way in which this new tool can be used to address the long-standing issue of the thermalisation times. From our investigation one can infer that Shannon entropy is a good figure of merit to study the dynamical onset of thermalisation in a closed quantum system. Within this picture, the time-scale at which thermalisation should occur for Here we present the full derivation of the equilibrium equations, using the Lagrange multipliers’ technique. Our purpose is to find the distribution which maximises Shannon entropy of an observable We present here the derivation, in the general case of a mixed state in which qn gives three equations, of which only two are independent: The derivatives with respect to the Lagrange’s multipliers Instead of using these equations, we use the two following independent linear combinationswhich give the two equilibrium equations that we used in the main textHow to cite this article: Anzà, F. and Vedral, V. Information-theoretic equilibrium and observable thermalization. Sci. Rep.7, 44066; doi: 10.1038/srep44066 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


We present a method by which the spectral intensity of an ultrafast laser pulse can be accumulated at selected frequencies by a controllable amount. Using a 4-f pulse shaper we modulate the phase of the frequency components of a femtosecond laser. By inducing femtosecond filamentation with the modulated pulse, we can concentrate the spectral amplitude of the pulse at various frequencies. The phase mask applied by the pulse shaper determines the frequencies for which accumulation occurs, as well as the intensity of the spectral concentration. This technique provides a way to obtain pulses with adjustable amplitude using only phase modulation and the nonlinear response of a medium. This provides a means whereby information which is encoded into spectral phase jumps may be decoded into measurable spectral intensity spikes. The production of femtosecond laser pulses has played a significant role in the advancement of modern science. In addition to their ultrashort pulse duration, femtosecond laser pulses offer a broad spectral bandwidth and a high instantaneous intensity for each pulse24610111531823242718In this article, we investigate an approach using phase only pulse shaping with femtosecond filamentation to convert energy from one part of the spectrum of an ultrafast laser pulse to another part of the spectrum. This method may also be used as a possible way to communicate information. In particular, we demonstrate experimental and numerical results wherein the spectral amplitude of a femtosecond laser pulse is accumulated by a controllable amount at selected frequencies. These results have direct impact on the use of femtosecond lasers and filamentation in communication schemes, since in this method, information can be encoded onto a laser pulse with a phase mask, and decoded again as measurable intensity spikes.A direct result of the broad bandwidth associated with femtosecond pulses is the ability to shape the temporal profile by modulation of the spectral components. This temporal shaping can be done using a 4-f pulse shaper, which consists of a diffraction grating to spatially disperse the pulse into separate frequency components, a lens to perform a spatial Fourier transform, a spatial phase or amplitude mask to modulate the shape, and another lens and grating to recombine and collimate the pulse31et al. as a way to detect the onset of two photon absorption33One technique that can be implemented with shaped femtosecond pulses is spectral hole filling, which was developed by Warren In this paper, we present a technique similar to spectral hole overfilling in the regime of femtosecond filamentation. Here, the effect is driven by a phase shift applied by a pulse shaper to a narrow band of frequencies in the pulse, rather than by a spectral hole. While femtosecond filamentation is accompanied by the generation of new frequencies, we focus here on the role and importance of intensity dependent attenuation in the process of amplitude concentration. This is because of the key role that nonlinear absorption plays in filamentation in waterA(ω), whereA laser pulse can be completely described by its Fourier decomposition E(t) is the electric field, ω is the angular frequency, and E(t). In this experiment, a pulse shaper performs a spectral transformationHere δω is the width of a narrow spectral window about the center frequency ω0. Note that if the applied phase shift is ϕ = π, the multiplicative factor becomes −1, denoting a phase flip. After this transformation, the pulse can be written in terms of a superpositionwhere eiϕ with 0), this equation is equivalent to the explanation for spectral hole overfilling discussed previouslywhere Π is the unit box function. Note that in the case that the applied phase shift is replaced by a spectral hole  part of the pulse. In the  limit of total attenuation of the short pulse and no attenuation of the long pulse, the observed intensity spectrum of the pulse will be proportional to |(1 − eiϕ)A(ω)|2 over the modulated bandwidth, which for the case of a phase flip (ϕ = π) is |2A(ω)|2, a factor of 4 greater than the pulse before the nonlinear propagation. In this manner, a time-domain attenuation process can cause intensity of the pulse to be concentrated at selected frequencies in the spectrum. This is illustrated in If the short pulse is intense enough to undergo nonlinear loss mechanisms while the long, less intense pulse only undergoes linear loss, the π phase shift (i.e. a phase flip) to a narrow spectral region  of a 50 fs laser pulse , we observe a sharp peak arise in the emission spectrum of a femtosecond filament in the forward direction. The filament was approximately 7 cm long. This peak has a strong dependence upon the phase shift applied by the pulse shaper. As the phase applied is scanned from 0 to π, the peak rises to a maximum, and then disappears again as the phase is scanned further to a 2π phase shift. The measured spectra for π and 2π phase shifts are shown in 314π phase step is applied within two pixels width (200 μm). Evidence of this is shown in the spectrum of the shaped laser pulse without filamentation  also focuses, but not nearly as much. Furthermore, ripples are observed in the trailing edge. This asymmetry between the behavior of the leading and trailing edges of the pulse is due to the plasma trail that is left in the wake of the filament.From the numerical results, insight to the dynamics of this effect are attained. In Integration of the spectrum of the various components of the pulse yields the energy contained in each component as a function of propagation distance. These are shown in Furthermore, in simulation and experiment, the frequency of the peak generated by the amplitude concentration moves according to the frequency of light being modulated. This is achieved experimentally by simply scanning the modulating pixels across the spatial light modulator, and results are shown in π phase shift is applied experimentally to two pixels with a gap between them in the spatial light modulator. In π phase shift. Thus, to within the resolution limits of our spatial light modulator, we can control which frequencies to amplify.It is also possible to have multiple peaks as shown in the top row of π phase shift is applied to a laser pulse by a 4-f pulse shaper resulting in a pulse composed of a superposition of a long (narrow-bandwidth) pulse component with low intensity and a short (broad-bandwidth) pulse component with high intensity. Through intensity-dependent attenuation from femtosecond filamentation, energy is transferred into the spectral regions where the phase shift was applied. This amplitude accumulation process in femtosecond filaments is due to the nonlinear effects associated with filamentation; namely, nonlinear absorption due to ionization. It should be possible to generate similar results with any attenuating effect that has a similar threshold-like behavior, thereby attenuating the broad-bandwidth portion of the shaped pulse while leaving the narrow-bandwidth portion unaffected. Furthermore, the efficiency of this process may be improved by modifying the pulse characteristics  to increase the degree of nonlinear loss experienced by the high intensity component of the pulse.We have experimentally and theoretically demonstrated an example of amplitude concentration in a femtosecond filament. A Computer controlled spatial light modulators provide control over this result. Not only can the wavelength of the intensity spike be adjusted by choosing which pixel to modulate, but the height of the intensity spike can also be set by choosing the phase of the modulation applied. In this manner, it is possible to encode information into spectral phase jumps by the spatial light modulator. The information can then be decoded into measurable intensity spikes.μJ/pulse) is then focused into a 15 cm long tank of tap water using a 40 cm focal length lens . A filament is induced, and the light emitted in the forward direction is collected by an integrating cavity  and measured by an Ocean Optics USB 2000+ spectrometer (1.3 nm resolution). The intensity of the spectra were calibrated using a Coherent PM10 power meter. Changing the phase mask applied by the spatial light modulator alters the resulting spectrum of the filament’s forward emission. Note that it is important to consider chromatic dispersion in water, since the group-velocity dispersion (GVD) coefficient is large for these wavelengths. However, in the regime of our pulse parameters , chromatic dispersion cannot stop self-focusing and plasma generation38The experimental setup is depicted in In order to compare the initial spectrum of the laser pulse to the spectrum of the forward emission, measurements of both spectra are taken after the tank of water, thus accounting for linear absorption from the water. Filamentation is induced by the focusing from the 40 cm lens placed before the tank of water. Thus, by collecting the spectrum with and without this lens we are able to compare the emission spectrum of the shaped and unshaped filament to the laser pulse without filamentation.However, because the laser is focused into the water in one case and not in the other, coupling into the spectrometer requires an integrating cavity to collect the light emitted into the forward direction . Thus, the spectral measurements are comparable regardless of the focusing geometry. The intensity measurement of the spectrometer is also further calibrated by normalization using a power measurement for each case.Power loss due to reflection from the uncoated focusing lens also introduces inconsistency when comparing the intensity of the spectrum with the lens to the spectrum without it. We measured and accounted for this power loss in the normalization process of the data. Thus, we have obtained a calibrated measurement of spectral intensity for shaped and unshaped laser pulses with and without filamentation.A ≡ A, modified to include ionization effects2342Our experimental results are compared to theory via numerical simulations where we use the generalized nonlinear Schrödinger equation for the field envelope r is the radial coordinate, z is the propagation coordinate, ω is the radiation frequency, n(ω) is the frequency dependent linear refractive indext is the retarded time, ω0 is the central frequency of the pulse, n2 = 2 × 10−4 cm2/TWHere Ionization effects are included through the t to ω, e is the electron charge, m is the electron mass, μ0 is the vacuum permeability, τc is the electron momentum transfer time, Nat = 3.3 × 1022 cm−3 is the number density of water molecules, W(|A|2) is the single-molecule photoionization rate  is found from the equationwhere z = −5 cm). The shape of the input pulse without a phase flip is calculated from experimental spectra, assuming the pulse is Fourier-limited at the cell entrance. While the experiment may deviate slightly from this assumption, the results should remain similar because of the robust nature of filamentation above threshold. The key point here is that the main pulse is well above threshold while the phase-shifted part of the pulse is well below threshold. These simulations have been performed in parallel codes using supercomputer complex of Lomonosov Moscow State University.which accounts for photoionization and impact ionization. Simulations are started 5 cm before linear focus .Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Intrafraction organ motion during the dynamic delivery of intensity‐modulated radiation therapy (IMRT) treatment of lung tumors may cause unexpected hot/cold spots within the target volume, due to the interplay effect between tumor motion and multileaf collimator (MLC) leaf motion. In the past, this has been investigated through theoretical analysis, computer simulation, and experimental measurement using an ionization chamber dosimeter. In the work presented here, the interplay effect was studied experimentally in 2D, using Kodak EDR2 films. A five‐field lung IMRT plan was delivered to a solid water phantom with embedded film. The phantom was placed on a motor‐driven platform with a sinusoidal motion to simulate the respiration‐induced tumor motion. The delivery of each field began at one of eight equally spaced initial breathing phases. The dose distribution for each treatment fraction was estimated by combining the dose distributions for all fields with randomly sampled initial breathing phases. The dose variation caused by the interplay effect was estimated by looking at the dose values from 1000 trials of 30 fractions. It was found that, on a day‐to‐day basis, the standard deviation of the dose to a given pixel in the high‐dose region could be as high as 2% to 4% due to the motion interplay effect. After 30 fractions, the standard deviation in the dose to each pixel is reduced to 0.4% to 0.7%. However, compared to the static delivery, the dose distribution from a 30‐fraction case in the presence of motion shows some underdosing in the region of interest. We found that the maximum dose in the target remains within 1% of the maximum dose in the static case, but the minimum dose in the target is most likely to be about 6% lower than the static case. Our results indicate that there can be some underdosing of the tumor due to the interplay effect in lung IMRT delivery over the entire course of a 30‐fraction treatment.PACS number: 87.53.Mr The reluctance is due to organ motion effects, including dose blurring effect and interplay effect.The goal of radiotherapy treatment is the placement of a high dose within the target area(s) with minimal dose accumulated in healthy tissues and organs. A proven method for improving the conformality of a dose distribution is intensity modulated radiation therapy (IMRT).–4 ClThe blurring effect is a convolution of the dose distribution delivered to a static target with a motion kernel and is, consequently, an issue for any delivery technique. Dose blurring is most important at the edges of the treatment volume, where the dose gradient is high. Therefore, a sufficient safety margin should be used.(–) This effect is only an issue for dynamic delivery techniques (including step‐and‐shoot IMRT) and may cause hot/cold spots within the target as well as outside it. Previous experimental work used point measurements and/or a single beam only. This work expands on those earlier studies by using Kodak EDR2 film to estimate the delivered dose distribution in an axial plane in the presence of organ motion for a multifield, multifraction IMRT treatment.The interplay effect is a combination of tumor motion and beam motion (as it is shaped by a dynamic multileaf collimator (MLC)) and has been studied both theoretically and experimentally.–16 T(–) For the irradiation, we placed a NOMOS IMRT QA phantom on the platform. Kodak EDR2 film was placed within the phantom in an axial orientation using a 3D square to ensure reproducible alignment  with a frequency that is determined by the current supplied to the motor. Although lung tumors tend to move in elliptical paths,–19 FFor the motion studies, the phantom was set up on the treatment table using the in‐room lasers. The platform motor was then turned on and the irradiation was performed beginning at one of eight equally spaced breathing phases for each field. The different starting phases were used to simulate a clinical situation in which the therapist turns the beam on at random starting phases. The phase was determined visually using a closed‐circuit video monitoring system. This was repeated for all five fields and for all eight phases to obtain a total of 40 films. The films were then scanned to digital format for analysis using a VXR‐16 16‐bit film scanner  and the WP700 software .Due to a feature of the scanner, the films had to been fed with one corner first . The angle of film during scanning varied; therefore, the digital images showed the field edges at different angles. For a proper comparison, the field images had to be rotated to the same orientation. A program was written in Interactive Data Language (IDL)  to detect the field edges and reorient the 40 images. From our experience with the reorientation procedure, we estimate the error to be less than one pixel (1 mm) in any direction. Since this is a study of dose distributions and not single‐point measurements, the error associated with the field reorientation is negligible. In addition, the digital reorientation of the field helped correct for any manual misalignment in the initial placement of the film in the solid water.Two quantities were studied:andTD1{μ} is the total dose distribution after a single fraction, and TD30{μ} is the total dose distribution after 30 fractions. Here, j represents the field (1 to 5), m is the fraction (1 to 30), and μ is a random integer between 1 and 8, representing the initial motion phase. {μ} is the set of μ's for a given calculation. The results can be subtracted from the static distribution, TDS, to calculate the difference. An example of TDS−TD1{μ} for a randomly selected μ is shown in Fig. −9.8% to +15.4% of the total prescribed dose. Calculations of TD1{μ} for different starting phases can also be compared to each other. Figure −6.5% to +4.4% of the total prescribed dose. The latter calculation can be repeated many times with a random sampling of initial motion phases for the platform to find the standard deviation of a single fraction. The standard deviation of the dose distribution at each pixel for 1000 trials is shown in Fig. where eld 1 to , m is thTD30{μ}. Figure The same analysis was done for The daily dose variation can be significant due to motion. The standard deviation of the differences from 1000 trials ranges from 1.2% to 5.4% over the entire film and from 2.0% to 3.8% within the region of interest (the 90% static isodose curve). However, after 30 fractions, the variation is reduced to less than 1%, and the range is between 0.36% and 0.71% within the region of interest. This is due to the canceling out of hot/cold spots when many fractions are combined. These results compare favorably with a previous experiment performed using an ion chamber for measurement.The probability density distributions of maximum, minimum, median, and mean dose values within the 90% static isodose curve for 1000 trials of single fraction treatments are shown in Fig. (<1%) standard deviation for every pixel. The results are similar to the single‐fraction case. The peak of the maximum dose is just below (<0.5%) that of the static case. The minimum dose distribution peaks well below (~6%) that of the static case. Both the median and mean distributions peak below (~2%) those of the static value. The dose distributions from several 30‐fraction deliveries will not vary much due to the motion. However, there is slight underdosing of the region of interest, by several percent, in the presence of motion, even for the 30‐fraction delivery.The probability density distributions of maximum, minimum, median, and mean dose values within the 90% static isodose curve for 1000 trials of 30‐fraction treatments are shown in Fig. ±0.25 s, or 22.5°, along the mechanical wheel. Previous simulations suggest that a smooth function describes the change in dose with change in initial phase.The visual method of choosing the eight sample points in the breathing cycle did not introduce any significant uncertainty in this study. The mechanical wheel that drives the sinusoidal motion of the platform was broken into eight sections. If one looks at the wheel as a 360° circle, each section is 45°. The period of the motion was approximately 4 s, which implies that a new section passed every 0.5 s. To estimate the uncertainty in the initial phase, we determined that we were able to engage the beam at least within The results from the film measurements included several sources of uncertainty. The film processing and the conversion from optical density to dose introduced uncertainties that are inherent in EDR2 film. In a recent study, the variation in the sensometric curve for EDR2 film was found to be less than 4% for a 6‐MV photon beam. These conclusions are in agreement with our previous study using an ion chamber for measurement.The interplay effect between organ motion and IMRT delivery with a dynamic MLC was studied using Kodak EDR2 film and a platform moving in a sinusoidal pattern. It was determined that possible hot/cold spots in the target region due to this effect become mostly blurred out over 30 fractions. However, there is the possibility of underdosing the tumor by several percent in the presence of motion. We would also like to point out that patient breathing is, in general, not as regular in amplitude and frequency as the moving platform in our experiment. In order to ensure regularity, a method of breath coaching may have to be used with patients.,22 TThis work was partially supported by grants from Varian Medical Systems, Inc., and the Whitaker Foundation.


Glenoid bone loss and capsular deficiency represent critical points of arthroscopic Bankart repair failures. The purpose of this study was to evaluate an all-arthroscopic bone block procedure associated with arthroscopic subscapularis augmentation (ASA) for treating gleno-humeral instability with glenoid bone loss (GBL) and anterior capsulo-labral deficiency. Our hypothesis was that these two procedures could be combined arthroscopically. The feasibility of this technique and its reproducibility, and potential neurovascular complications were evaluated.A tricortical bone graft was harvested from the cadaveric clavicle, and in one case a Xenograft was used. An anterior-inferior GBL of about 25% was created. Two glenoid tunnels were set up from the posterior to the anterior side using a dedicated bone block guide, and four buttons were used to fix the graft to the glenoid. The subscapularis tenodesis was performed using a suture tape anchor. Afterwards, the shoulder was dissected to study the relationship between all portals and nerves. The size of the bone block, its position on the glenoid and the relationship with the subscapularis tendon were investigated.In all seven specimens (five left and two right shoulders), the bone block was flush with the cartilage and fixed to the anterior-inferior part of the glenoid. No lesions of the surrounding neurovascular structures were observed. No interference was found between the two bone block tunnels and the anchor tunnel used for the tenodesis.This study demonstrated the feasibility and reproducibility of this combined arthroscopic technique (bone block associated with ASA) in the treatment of anterior shoulder instability associated with anterior bone loss and anterior capsular deficiency. The etiology and patho-mechanics of recurrent gleno-humeral dislocations are not completely known  was harvested from the proximal humeral epiphysis of the horse. The graft was completely deantigenated enzymatically, using Zimoteck. The graft can be pre-formed with the holes for the buttons, thus allowing greater precision and reduced operating times  were advanced until they laid flat on the bone block. The graft was tipped to allow insertion into the 15 mm cannula Fig. . The guiThe posterior round endobuttons were advanced using a sliding knot until they were flush with the posterior face of the glenoid. A suture tensioner device was used to secure the posterior round endobuttons. Once the implant was tensioned, we secured it with half hitches and cut suture tails   Fig.  in all crs) Fig. . Then, ors) Fig. . A punchrs) Fig. . While trs) Fig. . For a gAll seven specimens were dissected at the end of the two procedures to verify the graft stabilization anteriorly and posteriorly with the four buttons using a grasper, to assess the covering of the tendon on the graft and its position on the glenoid edge, and to identify any interference between the two glenoid tunnels and the anchor for the subscapularis tenodesis; the contact surface between the anterior part of the glenoid and the bone graft was measured using a ruler. Finally, we investigated the neurovascular structures in relation to the gleno-humeral joint.All procedures were performed by 2 accredited and experienced surgeons with specific skills in shoulder arthroscopy and on specimen study (RR and MM).The average time required to prepare the graft was 30 min; this time is avoided in the case in which we used the preformed xenograft. The average time to perform the ASA-BB procedure on the specimens was 112 min (80–150 min); the shorter time was obtained using the xenograft. The management of the sutures and buttons through the graft and glenoid tunnel was not difficult. In one case, it was necessary to flush out the graft at the glenoid level using a motorized burr. We have had no complications or fractures in any cases.No interferences were noticed between portals and the cephalic vein anteriorly. The center of the graft was located in a subequatorial position. The contact surface between the anterior part of the glenoid and the bone graft was 80% of the surface area of the bone block in the first 2 cases and 90% in the other 4 cases. No evidence was found of soft tissue interposition between the bone graft and the glenoid. All the grafts were positioned 1 mm more medial with respect to the articular surface. No interference was found between graft tunneling and the anchor side for the subscapularis tenodesis. There was a good covering of the graft by the tendon and a good position of its fixation on the glenoid neck. At the end of bone block procedure the shoulder was not easily dislocable as before the procedure in presence of a glenoid bone defect of about 25%. After ASA procedure the humeral head resulted recentered and shifted posteriorly under arthroscopic view. There was no vascular damage to the anterior and posterior vessels. No interference with the axillary nerve anteriorly and the suprascapular nerve posteriorly was noted. The axillary nerve was located 35 mm to 55 mm (average 40.3 mm) from the inferior gleno-humeral portal. The suprascapular nerve was located 8 mm to 15 mm average 11 mm) from the two glenoid holes Fig. . The mus mm from This paper demonstrates the feasibility and reproducibility of the first all arthroscopic procedure to combining a glenoid bone graft augmentation according to Taverna  is safe and easily reproducible, it is our intent to conduct a clinical study. It is essential that this technique should be evaluated clinically before its application on a large scale.This study has several limitations. The number of specimens treated is very small, and both techniques were applied to the shoulders using specimens non-homogeneous by age, sex and non-comparable glenoid bone defects; no study for measuring the glenoid version of the specimen was done. New biomechanically detailed studies should be carried out, examining, for example, modification of external rotation, the friction between the subscapularis tendon and the graft, the humeral head position relative to the glenoid rotational center after the removal of the capsulolabral complex and after the creation of a GBL of about 25%. This would allow the evaluation of the recentering effect of the subscapularis tenodesis alone or in association with the bone block in different arm positions, from 0° to 60° of elevation. Moreover, all anatomical structures should be subjected to cycles of movement to test the biomechanics of the head in this new anatomical position, considering also the strength of the fixation systems for both bone and tendon. Last but not least, knowledge is very limited on the healing of the free bone block using the button system and on the healing of the subscapularis tendon on the glenoid rim.This is the first cadaver study to test the feasibility and safety of this new all-arthroscopic combined technique with bone block and ASA for treating gleno-humeral instability with glenoid bone loss of about 25% and anterior capsule-labral deficiency. Further studies have to be performed to assess the stable fixation of the bone graft, the re-centring of the humeral head and the restoration of shoulder stability and function.