Agentes Polivalentes Elementares (APEs). We assessed the contribution of the program to improved care–seeking and appropriate treatment of childhood febrile illness in Nampula Province.Large scale evaluations in several settings have demonstrated that lay community health workers can be trained to provide quality case management of childhood illnesses. In 2010, Mozambique introduced the integrated community case management (iCCM) strategy to reach children in remote areas with care provided through We used a post–test quasi–experimental design with three intervention and one comparison districts to compare access and appropriateness of care for sick children in Nampula province. We carried out a household survey in the study districts to measure levels of care–seeking and treatment of childhood fever after approximately two years of full implementation of the iCCM program in the intervention districts. We also assessed consistency of care with standard case management protocols comparing children receiving care from (APEs) to those receiving care from first–level health facilities.A total of 773 children 6–59 months with fever in the last two weeks were included in the study. In iCCM served areas, APEs were the predominant source of care and treatment; 87.1%  of children 6–59 months with fever who sought care were taken first to an APE and APEs accounted for 86.2% (95% CI 79.7–92.7) of all first–line antimalarial treatments. Public health facilities were the leading source of care in comparison areas, providing care to 86.1% (95% CI 79.0–93.3) of children with fever taken for care outside the home. Timeliness of treatment was significantly better in intervention areas, where 63.9% (95% CI 54.4–73.3) of children received treatment within 24 hours of symptom onset compared to 37.5% (95% CI 31.1–43.9) in comparison areas. Children taken first to an APE were more likely to receive a rapid diagnostic test (RDT)  and to have their respiratory rate assessed  compared to children taken to health facilities . Overall, 61.3% (95% CI 51.5–71.0) of children with fever receiving care from APEs received the correct drug within 24 hours and for the correct duration compared to 26.0% (95% CI 18.2–33.9) of those receiving care from health facilities.iCCM contributed to improved timely and appropriate treatment for fever for children living far from facilities. Trained, supplied and supervised APEs provided care consistent with iCCM protocols and performed significantly better than first level facilities on most measures of adherence to case management protocols. These findings reinforce the need for comprehensive efforts to strengthen the health system in Mozambique to enable reliable support for quality of case management of childhood illness at both health facility and community levels. An estimated 5.9 million children die each year before reaching their fifth birthday; about half of these deaths are caused by infectious diseases . Among cAgentes Polivalentes Elementares (APEs) who provide iCCM services to communities located 8–25km from the nearest health facility [Mozambique is one of just 12 low–income countries to achieve its Millennium Development Goal (MDG) of reducing child mortality by two–thirds or more between 1990 and 2015 [facility ,7.Although there is global evidence that CHWs are capable of providing quality iCCM services –10, therSave the Children (SC), with funding from the Canadian International Development Agency  provided support to the Mozambican MOH for implementing iCCM from 2009 to 2013, with a focus on malaria (fever) management, the leading cause of child deaths. We present the findings of a quasi–experimental evaluation of the APE iCCM program that compares levels of care–seeking and timely and appropriate treatment coverage for fever in an intervention area with a well–supported iCCM program to levels in a comparison area where the APE iCCM program had yet to be implemented. We also compare consistency of care provided by APEs and first level health facilities with established cases management protocols.In Mozambique, community–based health services are provided through the APEs. The APE cadre was established in 1978, but services were disrupted due to the protracted civil war, which ended in 1992 . In 2010Under the revitalized program, APEs receive 18 weeks of training organized into four blocks; iCCM is covered for one week during the third block . APEs arUnidade Sanitária. Children presenting with fever or a history of fever are tested for malaria with a rapid diagnostic test. Children between 6–59 months with a positive RDT for malaria receive artemether–lumefantrine (AL) and paracetamol from the APE. A child with a negative test is given paracetamol, and referred to the first level health facility. Children 2–59 months with cough/difficult breathing are assessed for fast breathing by counting breathes for one minute using a digital timer. A child with respiratory rate above the WHO age–specific cut–off point is classified as fast–breathing pneumonia and treated with amoxicillin dispersible tablets. Children aged 2–59 months presenting with diarrhea are treated with recommended doses of ORS and zinc.Under the iCCM protocol, APEs assess children 2–59 months for general danger signs as a first step . If geneAt first level health facilities, providers follow a similar algorithm based on WHO’s Integrated Management of Childhood Illness (IMCI) protocol. According to the protocol, all children presenting with fever should be tested for malaria with an RDT and if positive, given the first–line antimalarial (AL). Fever is treated with either paracetamol in suspension or tablets. Those presenting with cough/difficult breathing should be assessed by counting breaths for one minute using a timer (or if not available a watch or mobile phone). Under MOH protocols, those with fast–breathing pneumonia receive amoxicillin or cotrimoxazole in suspension (MOH protocol was amended in early 2011 to include amoxicillin as first line treatment). Children with diarrhea should receive ORS and zinc. First level health facilities typically provide IMCI services 5 days per week (Monday to Friday) from 7:00am to 3:00pm. However, health staff live on the facility grounds so in theory, they can attend to severely ill children or those with danger signs at any time. The first level facilities are usually staffed with a medical technician (Técnico de Medicina), or/and a general nurse or MCH nurse. Both nurses and medical technicians receive 30 months training. Medicines and supplies for treatment of child illness  are meant to be provided to facilities monthly through provincial and district medical stores.Save the Children provided support for iCCM implementation, with a focus on fever management, in 10 districts in Nampula province and five districts in Gaza province from 2009 to 2013. APEs satisfied national eligibility criteria including the ability to read and write in Portuguese and complete basic arithmetic. In 2010, SC trained and equipped 319 APEs across the 15 districts to deliver iCCM services. These APEs were trained before the MOH had finalized the curriculum and manuals for the revitalized APE program, a task which was completed in October 2011. Thus, the first group of APEs trained by SC received six days of iCCM training based on training modules developed by SC together with the MOH. The training included a mix of classroom exercises and clinical practical sessions to provide the necessary knowledge and skills related to iCCM. Later, this iCCM module was adapted and incorporated into the larger, national APE curriculum and training package. The APEs received a week long refresher training in March 2012.Training activities were implemented using a cascade model, in which SC and MOH master trainers trained health facility staff and SC–employed district coordinators, who in turn trained the APEs At the end of the training, APEs were administered a clinical competency assessment and APEs who passed were awarded certificates upon completion of the training and provided a kit of essential drugs and supplies. The APEs kept the kit at the health post, which served as iCCM delivery site as well. The kit included: medicines specified by the national iCCM protocol including AL, amoxicillin, ORS, and zinc; respiratory timers; job aids; and a treatment register. The APEs received stipend support from Save the Children and MOH .During the project implementation period, SC provided technical support including development and adaptation of tools, training, monitoring, and supervision. Save the Children trained MOH staff at district and health facility levels in supervision and supply chain support. APEs were supervised monthly within their communities by district and facility based MOH staff trained on iCCM protocols, monitoring and supervision. SC placed staff at district level to support and mentor the MOH staff to supervise and monitor APEs. AL, amoxicillin, and malaria RDTs were procured by SC through local suppliers approved by the MoH. The medicines procured by SC were supplemented with medicines  from the MOH system. Additionally, SC transported these medicines and supplies from the provincial capital to the districts and, in some cases, to the APEs’ reference health facility. Medicines were procured and distributed to the APEs based on number of cases treated reported by APEs.Nampula province is located in the north of Mozambique and, as of 2013, had an estimated population of more than 4.7 million. Nampula province was chosen for the endline study given that more than 90% of under–five children targeted through SC support were located within the province. We conducted a household survey in areas with iCCM services in three intervention districts  that had received SC support and one comparison district, Mossuril, where the APE revitalization and iCCM program had yet to be rolled out  and 61 158 children under five. Mossuril, the comparison district, was selected for the evaluation as it was geographically proximate to the intervention areas (located adjacent to Monapo district) and had a similar health service profile, with a total population of 119 223 with 10 government health facilities.A cross–sectional household survey was conducted in Nampula province in November 2012 after approximately two years of program implementation. The sample size of 600 households from the three intervention districts and 600 households from the comparison district was powered to detect a 20% difference in fever  treatment between intervention and comparison areas, assuming a fever prevalence of 27% and baseline treatment of 42%. Households with children aged 2–59 months were selected using a two–stage sampling procedure. In intervention districts, 30 APE catchment areas were selected with equal probability (ten per district) and in the comparison areas 30 census enumeration areas that were at least 8 km from nearest health facility (and therefore eligible for implementation of iCCM program) were sampled proportional–to–size from a listing of all eligible enumeration areas. A mapping team sketched basic maps of each selected survey cluster prior to the start of fieldwork. The maps identified boundaries of each cluster, landmarks, and buildings to allow data collection teams to locate selected households. The catchment area population of the APEs ranged from a population of 500 to 2000, located 8–25km from the nearest health facility . Any APE catchment area exceeding 300 households was broken down into smaller units of 150–200 households and the unit containing the APE health post was selected for the household listing. Within each selected cluster, all households were listed and households with children 2–59 months were identified by asking the household head whether any children in that age range were resident; from those listings, 20 households with at least one child aged 2–59 months were selected using systematic random sampling. Within each selected household, one mother or caregiver was randomly selected to be interviewed regarding recent child illness and care–seeking behaviors.The questionnaire was modeled after the UNICEF Multiple Indicator Cluster Survey (MICS) questionnaire (version 4) and included three modules: household, caregiver, and children under–five . The queData collection was led by the National Institute of Statistics  in Portuguese) with technical support from SC. Data collectors with prior experience of conducting national household surveys were recruited and trained for six days, including one day of field practice. Data collection was completed in October and November 2012 by four teams of five members each, including a team leader trained to supervise the data collectors, review completed questionnaires, and perform the household sampling. Two field coordinators from INE and two from SC monitored data collection to ensure quality control of data. Data were entered into CSPro by a team of four data entry clerks and double data entry was used to ensure quality; any data discrepancies were reconciled prior to analysis.The data were analyzed in Stata IC 11.1 . Data analysis involved calculating frequencies and cross tabulations of care seeking, coverage and consistency of care indicators .Treatment coverage: Proportion of children 6–59 months with fever in the last two weeks who received AL.Timely and appropriate treatment coverage: Proportion of children 6–59 months with fever in the last two weeks who received AL within 24 hours of onset of symptoms.Consistency of reported care with standard case management protocols: APEs vs first–line health facilities as first place of careAppropriate assessment:Respiratory rate assessment for cough or difficult breathing: proportion of children aged 2–59 months with cough and fast/difficult breathing whose respiratory rate was assessed.RDT for fever: Proportion of children aged 6–59 months presenting with fever who were administered an RDTCommunication of results:RDT result communication: Proportion of children 6–59 months presenting with fever who were administered an RDT and whose caregiver were told the results of the test.Appropriate treatment of fever:Correct medication: proportion of children 6–59 months with fever who received AL.Rationale use of antibiotics: proportion of children 6–59 months with fever only who did not receive antibiotics.Timely treatment: proportion of children 6–59 months with fever receiving AL who initiated treatment within 24 hours of onset of symptoms.Correct duration: proportion of children 6–59 months with fever receiving AL who took AL for the recommended for 3 days.Overall appropriate treatment: proportion of children 6–59 months with fever who initiated AL treatment within 24 hours and took medication for three days.Provision of first dose and follow-up of children with fever treated by an APE:First dose: proportion of children 6–59 months who received AL from APE who took first dose in presence of APE.Follow–up: proportion of children 6–59 months who received AL from APE who returned for follow–up.We applied a standard set of metrics captured in household surveys to compare levels of care–seeking and treatment coverage in intervention and comparison areas  taken first to private clinics, pharmacies, drug shops, informal care providers, or public sector hospitals were excluded from the analysis to allow direct comparison of first level facilities with APEs and sick children who were taken for subsequent care after visiting an APE of first–line government facility (n = 25) were excluded as it would not be possible to differentiate clearly what care was provided by what provider.Ethical clearance was obtained for the survey from the Ministry of Health Bioethics Committee in Mozambique. Informed oral consent was obtained from every respondent and documented by interviewers on the survey tools.Among the 1200 households surveyed with at least one child aged 2–59 months, information was collected for 1531 (753 intervention and 778 comparison) among 1534 eligible children. Characteristics of households are presented in P = 0.003) (P = 0.007). Among those seeking care for fever from a formal public or private source, 87.9% (95% CI 82.6–93.2) received AL in intervention areas compared to 74.1% (95%CI 66.0–82.2) in the comparison areas. The largest differences between intervention and comparison areas were seen in the timeliness of treatment initiation. In iCCM areas where APEs were providing care in the community, 63.9% (95% CI 54.4–73.3) of children with fever initiated AL treatment within 24 hours of symptom onset whereas in comparison areas 37.5% (95% CI 31.1–43.9) of children with fever initiated AL treatment within 24 hours (P = 0.000). APEs were the predominant source of care and treatment in the intervention areas; 87.1% (95% CI 80.8–93.4) of children 6–59 months with fever who sought care were taken first to an APE, who accounted for 86.2% (95% CI 79.7–92.7) of all first–line antimalarial treatments. Public health facilities were the leading source of care in comparison areas, providing care to 86.1% (95% CI 79.0–93.3) of children 6–59 months with fever who were taken for care outside the home.A total of 773 children 6–59 months (346 intervention and 427 comparison) were reported to have fever in the two weeks before the survey. Levels of appropriate care–seeking from formal public or private providers for fever were significantly higher in areas with iCCM compared to those without iCCM  and to take AL for the recommended 3 days . Overall, 74.1% (95% CI 64.6–83.6) of RDT+ cases managed by APEs received the correct drug within 24 hours and took for 3 days compared with 36.0% (95% CI 21.0–51.0) of RDT+ cases managed by health facilities. The number of RDT– cases was too small  to analyze.We also looked at the results for the subset of children 6–59 months with RDT+ results. Of caregivers who received the RDT results, reported malaria positivity levels were high . Due to the higher rates of RDT testing and disclosure of results among children managed by APEs, 65.3% of children with fever cared for by APEs in the sample (162/248) were reported RDT+ compared to 29.5% of children with fever cared for by first level health facilities (86/292). Nearly all RDT+ cases received AL , but RDT+ children who received AL from APEs were significantly more likely to receive AL within 24 hours  took the first dose in the presence of the APE and 70.1% (95% CI 62.9–77.4%) returned to the APE for follow–up. Data were not available for first dose or follow–up for children with fever managed by health facilities.Our results demonstrate that trained and well–supported APEs implementing iCCM can contribute substantially to timely care and treatment of childhood illnesses in rural Mozambique. A cross–sectional household survey conducted after approximately two years of iCCM implementation showed higher levels of appropriate care–seeking in areas with iCCM services compared to similar areas without iCCM services. Critically, the provision of iCCM by community–based APEs contributed to timely treatment for fever, likely due in large part to bringing curative care closer to the home and reducing delays in seeking appropriate care. Timely treatment is especially important for children with symptoms of malaria and pneumonia, where treatment within 24 hours of symptom onset is linked to improved outcomes ,19. ChilOur findings provide evidence that well–supported APEs can deliver care consistent with country iCCM protocols. In study areas, the APEs provided care aligned with national guidelines and performed as well as or better than facility–based providers for measures of appropriate assessment, counselling and treatment. Children with fever taken first to APEs were significantly more likely to receive an RDT, to be counselled on the RDT results, and to receive treatment with AL than children taken to first–level facilities. Children receiving care from APEs were also more likely to have their respiratory rate assessed and inappropriate treatment with antibiotics for fever only was low, helping to allay concerns regarding the ability of CHWs to manage suspected pneumonia . HoweverThese results were achieved within a well–supported APE program, which is critical for interpreting the findings in the context of the future of iCCM programs implemented by MOH with minimal external support. The iCCM program in Nampula was implemented with support from Save the Children, which provided technical staff and transport to conduct monthly onsite supervision of APEs. In addition to supervision, the APEs in the SC program areas were well supported with a reliable supply of materials and medications (and not reliant on MOH supply chain). Program data collected through interviews, observations and record review for the 30 APEs in the selected intervention clusters alongside the household survey indicated that the majority of APEs had the necessary supplies and medicines for iCCM provision: 90% had a functional timer; 87% had RDTs in stock; 80% had AL in stock; and 80% had first–line antibiotics available . SuperviOur findings highlight the need for greater attention to the management of childhood illness at first level facilities and increased investment in broader health systems strengthening beyond short–term, mostly vertical supports . Poor adThis study is one of the first to our knowledge to use household surveys to assess aspects of consistency with iCCM/IMCI protocols. Specifically, the indicators on counting of respiratory rate, communication of RDT results, provision of first dose, and follow–up visits have not previously been measured in standard household surveys. Although these indicators have not been validated, they ask caregivers to recall noteworthy events during the examination and/or treatment course for a relatively short recall period of two weeks. A register review of activity documentation by APEs from the 30 intervention clusters found similar levels of recorded respiratory rate counting and RDT administration to that reported by caregivers during the household survey; 87% of APEs had RDT test results recorded for the five most recent cases of fever and 63% had respiratory rates documented for the five most recent cough cases . We propSeveral limitations should be recognized when considering our findings. The study design was constrained by limited funding and time for evaluation and we did not have a baseline against which to measure change over time. To obtain a sufficient sample size, we only sampled households in which a child aged 2–59 months was identified during household listing. Although care was taken to identify all such households during the household listing stage, errors in age measurement or absence of any respondent in these households may have excluded some eligible households from the sample. Additionally, our sample relied on the comparison of the intervention districts to one comparison district. This sampling strategy was necessary given the rapid national roll–out of iCCM in Mozambique, but can make the results challenging to interpret as one cannot quantify or account for the potential influence of local contextual differences . AlthougThis study demonstrates that well–trained and supported APEs providing iCCM significantly contributed to improved timely and appropriate treatment of fever in rural Mozambique. Demand for iCCM was strong as evidenced by high levels of utilization of APEs as first source of care in program areas. In addition, APEs provided care that was consistent with iCCM protocols and performed significantly better than first level facilities on most measures of adherence to case management protocols. These findings reinforce the need for comprehensive efforts to strengthen the health system in Mozambique to enable reliable support for quality of case management of childhood illness at both health facility and community levels.


The skin is the largest organ of the human body and can sense pressure, temperature, and other complex environmental stimuli or conditions. The mimicry of human skin's sensory ability via electronics is a topic of innovative research that could find broad applications in robotics, artificial intelligence, and human–machine interfaces, all of which promote the development of electronic skin (e‐skin). To imitate tactile sensing via e‐skins, flexible and stretchable pressure sensor arrays are constructed based on different transduction mechanisms and structural designs. These arrays can map pressure with high resolution and rapid response beyond that of human perception. Multi‐modal force sensing, temperature, and humidity detection, as well as self‐healing abilities are also exploited for multi‐functional e‐skins. Other recent progress in this field includes the integration with high‐density flexible circuits for signal processing, the combination with wireless technology for convenient sensing and energy/data transfer, and the development of self‐powered e‐skins. Future opportunities lie in the fabrication of highly intelligent e‐skins that can sense and respond to variations in the external environment. The rapidly increasing innovations in this area will be important to the scientific community and to the future of human life. First, we introduce the fundamental transduction mechanisms commonly used in e‐skins. Major technical improvements in e‐skins are described for the acquisition of excellent stretchability, sensitivity, and resolution properties for accurate tactile sensing. Additionally, we highlight the most recent breakthroughs in multifunctional e‐skins and summarize recent development trends and application forecasts.2Recently, electronic skin that can sense pressure, strain, shear forces, and twist deformation has attracted attentions. Effective signal transduction that converts external stimuli into an analog electronic signal is an important component of accurate quantitative monitoring. Traditional transduction methods  of a parallel plate capacitor, the ability to store a charge, is described by C = εA/d, where ε is the dielectric constant, and A and d are the area and the distance between the two electrodes, respectively. Traditional capacitive sensors have been commonly used to measure different forces by monitoring the changes in A and d for which the applied pressure or shear force can easily result in the variation of the distance or the area between the two conductive plates.The capacitance .Piezoelectricity refers to the production of electrical charges in certain materials under mechanical force due to the occurrence of electrical dipole moments. Dipole moments can be derived from the deformation of oriented noncentrosymmetric crystal structuresd33 values but low flexibility, whereas piezoelectric polymers display the opposite. To exploit flexible piezoelectric pressure sensors with high d33, certain groups have attempted a variety of approaches, including the construction of thin films of piezoelectric inorganics on flexible substrates,Piezoelectric inorganics typically exhibit high 2.4In addition to the mentioned methods, other novel transduction methods have been investigated for the expansive application of e‐skin. Optical pressure sensors, which can cause modification of the light intensity or wavelength between the light source and the terminal detectors with applied pressure, have attracted attentions for application in touch screens and visual displays.3Good flexibility and stretchability are significant for skin to maintain its pressure‐sensing ability under complex mechanical deformation and have inspired the development of flexible and stretchable pressure sensors for e‐skins. High flexibility can be obtained simply by employing thinner flexible substrates, whereas stretchability requires techniques that are more sophisticated, such as an island‐bridge structure design. In addition, key research goals are to obtain tactile sensors with high performance, high resolution, high sensitivity, and rapid response for various applications. In this section, we present a brief introduction to the structural design and functional exploration of flexible pressure sensors from different perspectives.3.1Compared with the traditional electronic devices that are fabricated on rigid semiconductor wafers, flexible and stretchable electronics are a topic of growing interest as alternative future electronics because of their potential applications in micro‐electromechanical systems (MEMS), robotics, human–machine interactions, and biological tissue sensing.FigureTo date, two common strategies have been used to improve the stretchability of the devices. The first method directly bonds thin conductive materials that have low Young's moduli to a rubber/elastic substrate, such as poly(dimethylsiloxane) (PDMS). Geometrical patterning and device designs, e.g., net‐shaped structures,−1 under stretching to 140%.−1 at 100% strain, based on rubber fibers covered with silver nanoparticles via electrospun technology for large‐scale production.The second method to further enhance the stretchability of electronics is to assemble the device using intrinsically stretchable conductors that are always fabricated by mixing conductive materials into an elastomeric matrix.3.2Large‐scale pressure sensor arrays are important for the application of future generations of e‐skin.Figure−2) with ultra‐flexible mechanical properties and remarkable electrical properties   without power consumption was reported by Fan et al.[[qv: 16b]] The basic operating mechanism of this device can be explained as follows. Charges transfer between the contact surfaces of two stacked polymer films due to their friction under mechanical stimuli resulting from the triboelectric effect, thus introducing an electric potential difference between the top and bottom electrodes deposited on the outer surfaces of the films because of electrostatic induction; hence, electrical signals are detected when the two electrodes are connected through a electrometer. By constructing microstructures on the contact surfaces, the pressure sensitivity of the flexible triboelectric generators was improved such that they could operate as self‐powered pressure sensors Figure11a.81 FigureFigureThe integration of a triboelectric sensor array was reported by Lin et al. for self‐powered tactile imaging Figure12.84 A4.2The ability to mimic the complex function of human skin is of tremendous interest in the development of artificial e‐skin. Functions in addition to pressure or tactile sensing are desirable to better adapt to the surrounding environment, including the abilities of self‐healing and temperature measurement, which are also key challenges for practical applications of e‐skin.FigureThe self‐healing property has currently attracted profound interest for robotic and prosthetic applications in the pursuit of a trait that resembles the human skin's ability to repair itself after injury.FigureThe development of a multi‐type force‐sensitive sensor that meets the requirements of high sensitivity and flexibility remains a challenge. Inspired by the interlocking biological structures in nature, such as cochlear hair cells, Pang and co‐workers created an ultra‐sensitive multifunctional sensor with two interlocked layers of high‐aspect‐ratio Pt‐coated nanofibers bonded to a flexible substrate Figure15a.10 FigureFigureTemperature‐sensing ability is another important capacity of human skin, which helps to maintain the thermal balance between the body and ambient surroundings and represents a significant breakthrough for the use of temperature‐responsive e‐skin to broaden the applications in human–machine interactions.FigureIn addition to the functions mentioned above that attempt to mimic human skin, such as strain, pressure, temperature, and humidity sensing, additional features of intelligent e‐skin should be exploited in the future beyond the basic functions and physiognomy of human skin, which are the advantages of e‐skin.4.3Wireless communication is commonly used in our daily lives. This communications approach can eliminate the restrictions of disorganized wires and cables and enables the transfer of information between unconnected objects. To exploit wireless technology, certain research groups have pursued applications of e‐skin sensors for wireless sensor arrays, wireless energy transfer, and wireless data communication.FigureBao and co‐workers demonstrated a flexible wireless sensor array that can monitor and map the pressure variation in real time Figure19a.[[q5In this review, we highlight the primary approaches used to construct more flexible and stretchable sensors and the efforts toward the delivery of high‐performance e‐skin. Recent noteworthy achievements in the use of functional materials and the optimization of device design are convincing solutions to mimic the unique features of human skin. The pressure sensitivity of sensors is dramatically enhanced with the use of transistors with microstructured gate dielectrics, which enables the active matrix to reduce signal crosstalk between pixels and promotes rapid addressing and low‐power consumption. In addition, the use of oriented piezoelectric NWs and NBs with high intrinsic piezoelectricity and good mechanical stability accelerates the development of high‐resolution sensing arrays that extend beyond the capabilities of human sensing. Moreover, the fabrication of multifunctional e‐skins is an essential research goal to satisfy industry requirements for various applications. Highly integrated electronics for the detection of multiple stimuli are the subject of many investigations. With the aid of newly emerging technologies, e.g., wireless technology and the preparation of ultrathin sensors, these efforts have received substantial attention in the field of health monitoring and medical implant services.However, certain challenges remain for practical applications. For example, new materials and a novel transduction mechanism should be further investigated to realize a tunable pressure measurement range. Although ultra‐sensitive sensors have been reported in recent studies, the pressure measurement range should be further expanded to satisfy the demands of various applications. Moreover, the production of devices with low‐power consumption or self‐powering ability remains a topic worthy of in‐depth study because the energy crisis is currently one of the largest challenges in our society. Additionally, different types of artificial smart e‐skins are urgently required for emerging fields in healthcare, including health monitoring, prosthesis techniques, and clinical medicine. Similar to real human skin that can adjust and provide feedback in real time according to the different types of external stimuli via the peripheral nervous system, future e‐skins will also intelligently respond to variations in the external environment based on novel information transmission technology, which has a bright future for the development of e‐skins.


Bangladesh achieved Millennium Development Goal 4, a two thirds reduction in under–five mortality from 1990 to 2015. However neonatal mortality remains high, and neonatal deaths now account for 62% of under–five deaths in Bangladesh. The objective of this paper is to understand which newborns in Bangladesh are receiving postnatal care (PNC), a set of interventions with the potential to reduce neonatal mortality.Using data from the Bangladesh Maternal Mortality Survey (BMMS) 2010 we conducted logistic regression analysis to understand what socio–economic and health–related factors were associated with early postnatal care (PNC) by day 2 and PNC by day 7. Key variables studied were maternal complications  and contact with the health care system . Using data from the BMMS 2010 and an Emergency Obstetric and Neonatal Care (EmONC) 2012 needs assessment, we also presented descriptive maps of PNC coverage overlaid with neonatal mortality rates.There were several significant findings from the regression analysis. Newborns of mothers having a skilled delivery were significantly more likely to receive PNC  1.81, 2.58; Day 2: OR = 2.11, 95% 95% CI 1.76). Newborns of mothers who reported a complication were also significantly more likely to receive PNC with odds ratios varying between 1.3 and 1.6 for complications at the different points along the continuum of care. Urban residence and greater wealth were also significantly associated with PNC. The maps provided visual images of wide variation in PNC coverage and indicated that districts with the highest PNC coverage, did not necessarily have the lowest neonatal mortality rates.Newborns of mothers who had a skilled delivery or who experienced a complication were more likely to receive PNC than newborns of mothers with a home delivery or who did not report a complication. Given that the majority of women in Bangladesh have a home delivery, strategies are needed to reach their newborns with PNC. Greater focus is also needed to reach poor women in rural areas. Engaging community health workers to conduct home PNC visits may be an interim strategy as Bangladesh strives to increase skilled delivery coverage. The prevention of neonatal mortality has become a global priority because of the high mortality experienced by newborns and the difficulty in achieving improvements in their survival. Neonatal mortality now accounts for 45% of under–five mortality which translates to 2.8 million deaths within the first 28 days of life. On a global level neonatal mortality rates have declined from 33 to 19 deaths per 1000 live births (from 1990 to 2015), but this 47% reduction is much less than the 58% reduction seen in deaths among post–neonatal children under–five [Every Newborn is an action plan focused on enabling countries to prevent neonatal deaths and stillbirths [Every Woman Every Child movement and includes a vision, goals, strategies, and priorities for reducing newborn and stillbirth deaths. To achieve these goals, Every Newborn lays out key strategic objectives: 1. Improving care at birth, 2. Improving the quality and equity of maternal and newborn care, 3. Reaching every woman and newborn and achieving impact at scale, 4. Harnessing the power of parents, families and communities, and 5. Counting every newborn through measurement, program–tracking and accountability. Referral and follow–up care for low birth weight and sick newborns is also crucial given that prematurity and low birth weight are major predicators of neonatal mortality.llbirths . The plaA continuum of services is needed to enhance newborn survival. Essential newborn care (ENC) involves care soon after birth and includes hygienic care, thermal control, support for breastfeeding and resuscitation with bag and mask, if needed . Such inUnder–five mortality in Bangladesh has been steadily declining from 144 deaths per 1000 live births to 38 deaths per 1000 live births in the period between 1990 and 2015 [Promotion of PNC has been emphasized in the National Neonatal Health Strategy and Guidelines (NNHS) of Bangladesh, and PNC is provided free of charge at government health facilities. PNC is provided both at health facilities and during home visits by community health workers in efforts to make the service accessible from the community to tertiary level. During home visits community health workers focus on the i) promotion of newborn care ; ii) promotion of nutrition & family planning counseling to mothers; iii) providing information about danger signs of both mother and newborn; iv) Identification of danger signs in newborn and referral; v) support for breastfeeding; and vi) care of low birth weight infant  ,8.Studies in Bangladesh have found that socioeconomic factors such as education ,10 and wThe main aim of this study is to delve deeper into the question of which newborns in Bangladesh are receiving PNC by exploring not just socio–economic factors but also health–related factors, including maternal complications and contact with the health system. Our aim is to understand whether these factors, which have not been extensively studied in the literature, are associated with PNC. A secondary aim is to use maps to descriptively present geographic variability in PNC coverage and neonatal mortality. Maps can be a useful means to pinpoint geographic areas which need more programmatic focus.Data came from the 2010 Bangladesh Maternal Mortality Survey (BMMS), a large–scale survey of 175 000 households . The BMMData for the maps came from the BMMS 2010 as well as from a 2012 Needs Assessment of Emergency Obstetric and Newborn Care (EmONC) . The BMMThis study was reviewed by the Institutional Review Board (IRB) at the University of North Carolina at Chapel Hill and was exempted from needing ethics review approval because of the secondary nature of the analysis.We calculated simple weighted descriptive statistics and chi–square analyses on all predictor and demographic variables, comparing women who reported receiving PNC on or before day 7 and on or before day 2 (early PNC) to those who did not. The sample for early PNC is a subset of the larger PNC on or before day 7 sample. Early PNC was defined as within a day for facility births and within two days for non–facility births. The WHO indicates that PNC should be given to newborns within 24 hours for both facility births and as soon as possible for non–facility births ,20. We tOur key predictor variables were focused on access to maternal health services and the presence of complications. In terms of maternal health services we included receipt of ANC, type of delivery attendant (Skilled Birth Attendant (SBA) or non–SBA), place of delivery (facility vs non–facility). A SBA was defined according to the World Health Organization’s definition as “an accredited health professional – such as a midwife, doctor or nurse – who has been educated and trained to proficiency in the skills needed to manage normal (uncomplicated) pregnancies, childbirth and the immediate postnatal period, and in the identification, management and referral of complications in women and newborns” . We, thuWe performed weighted logistic regression models predicting receipt of the PNC outcomes, controlling for maternal age, parity, highest level of education, urban residence, marital status, and wealth quintile. The wealth index was constructed from data on ownership of household items including bathroom facilities, roofing, and flooring. Each asset was assigned a weight (factor score) generated through principle components analysis. Each household’s scores were then summed; individuals were ranked according to the total score of the household in which they resided ). All an2 analyses of the key independent variables and PNC with neonatal mortality. Studying associations between PNC and neonatal mortality, however, has its limitations. The data do not allow for a determination of whether or not deaths on the first day of life occurred to newborns before they were even eligible for PNC [Descriptive maps of PNC by day 7 and early PNC were interposed with data on population–level neonatal mortality and facility–level neonatal mortality to present subnational level variation in PNC coverage and neonatal mortality. We also performed χ for PNC . For exaPNC is a package of interventions intended for all newborns and has both a preventative focus and curative focus. In our study of PNC in Bangladesh we find that newborns whose mothers had a facility delivery or who had a complication were likely to have a PNC check than newborns of mothers who delivered at home or did not have a complication. Given that 79% of women in our sample had a home birth, efforts are needed to ensure all newborns are reached.PNC for newborns may not always be perceived to be necessary by mothers and their families in Bangladesh ), unlessTraditional practices may prevent many mothers from leaving their homes for up to 40 days after delivery ,25. DuriIn addition to identifying methods to reach more individual newborns, it is also important to study PNC coverage at a subnational level to enable countries to address geographic inequities. In Bangladesh there is wide variation in PNC coverage. Understanding why some districts have lower coverage than others can help inform intervention strategies. Traditional practices such as seclusion of the mother and newborn may be more prevalent in some districts than others, and thus engagement with communities on the importance of PNC (whether in a facility or in the home) may be particularly helpful.Our maps also revealed that districts with the highest PNC coverage did not necessarily have the lowest neonatal mortality and vice versa. We further explain this finding through bivariate comparisons of our key independent variables and PNC with neonatal mortality. The findings indicated significantly higher neonatal mortality when there is a PNC by day 2 check, maternal complication and delivery with a skilled birth attendant. Families in Bangladesh seem to view PNC as a service needed only when there is a problem with the mother or newborn. According to the BMMS 2010, 56% of mothers whose newborns did not receive PNC, indicated the reason was that the service was “not needed” . UnfortuThere are several limitations to this study including our inability to include certain measures including neonatal complications, four or more ANC visits and birthweight. Though we looked at bivariate associations of PNC with neonatal mortality, there could be some left censoring of the data in that some newborns could have died before they were eligible for PNC . AnotherBased on the findings of this study, several programmatic recommendations can be made. Both formal health workers and community health workers should provide PNC, a service essential for both for its preventative and curative elements. Particular efforts are needed to reach rural and poor women. Bangladesh has already taken relevant steps to reduce neonatal mortality by developing a National Newborn Health Strategy, which includes PNC provided by community health workers as a national health sector program approach . Importa


The mean maximum calculated skin and rib doses did not vary greatly between eBx and Iridium. By contrast, the doses to the ipsilateral lung and the heart were significantly lower with eBx as compared with Iridium (p<0.0001). The total nominal dwell times required for treatment can be predicted by using a combination of the balloon fill volume and planned treatment volume (PTV). This dosimetric comparison of eBx and Iridium sources demonstrates that both forms of balloon‐based brachytherapy provide comparable dose to the planning target volume. Electronic brachytherapy is significantly associated with increased dose at the surface of the balloon and decreased dose outside the PTV, resulting in significantly increased tissue sparing in the heart and ipsilateral lung.The objective of this study has been to compare treatment plans for patients treated with electronic brachytherapy (eBx) using the Axxent System as adjuvant therapy for early stage breast cancer with treatment plans prepared from the same CT image sets using an Ir‐192 source. Patients were implanted with an appropriately sized Axxent balloon applicator based on tumor cavity size and shape. A CT image of the implanted balloon was utilized for developing both eBx and Ir‐192 brachytherapy treatment plans. The prescription dose was 3.4 Gy per fraction for 10 fractions to be delivered to 1 cm beyond the balloon surface. Iridium plans were provided by the sites on 35 of the 44 patients enrolled in the study. The planning target volume coverage was very similar when comparing sources for each patient as well as between patients. There were no statistical differences in mean %V100. The percent of the planning target volume in the high dose region was increased with eBx as compared with Iridium PACS numbers: 87,53.Jw, 87.55.dk, 87.55.D‐,87.56 b‐,87.56.bg Approximately 60% of these cases will have cancer confined to the breast. Breast conserving therapy (BCT) for localized breast cancer is widely accepted and involves surgery usually followed by radiation treatment. However, over 40% of women choose a mastectomy over BCT and many who do choose BCT forego the radiation therapy component of their treatment program. Reasons cited often include travel distance to a radiation treatment center and time away from home and work for a six to seven week course of whole breast external beam radiation.(–)Breast cancer will be diagnosed in an estimated 192,370 women in 2009.1 ApprSeveral methods of accelerated partial breast irradiation (APBI) have been developed to irradiate a smaller volume of tissue with a larger dose per fraction. This allows the prescription dose to be delivered over the course of one week with an expected decrease in dose to normal tissue including the heart, lungs and contralateral breast compared with whole breast external beam therapy. Interstitial multi‐catheter brachytherapy has demonstrated that APBI can be effective; however, technical challenges have prevented this form of APBI from being widely adopted.7 reported results of an initial intracavitary APBI study and no local recurrences (either at the tumor bed or elsewhere in the breast) or regional recurrences have occurred in the 36 patients who have been followed for a median of 5.5 years. However, the use of radioisotopes requires a shielded radiation vault and a high‐dose rate (HDR) afterloader unit, and many patients are unable or unwilling to travel to a fully‐equipped facility.Balloon‐based brachytherapy has achieved wider acceptance due to the ease of use. The MammoSite balloon‐based treatment utilizes an Iridium‐192 source to provide APBI, and local control rates at five‐year follow‐up have been good. Benitez et al.8 repo Early results of the first clinical study of the Axxent eBx system were favorable with complication rates similar to Ir‐192 APBI.The Axxent balloon‐based treatment uses a miniature X‐ray source operating at 50 kVp, which reduces the shielding requirements and avoids the handling and storage constraints required for radioisotope sources, making widespread use of APBI economically feasible.10 Ear have compared the dosimetric characteristics of these two balloon‐based systems; however, in those studies the eBx treatment plans were simulated from patients actually treated with an Ir‐192 source. We herein report the dosimetric comparison of these two forms of APBI that starts with eBx treatment plans for patients with localized breast cancer.Several studies9 haveTreatment plans for 35 patients were included in these analyses. Patients were enrolled in a study protocol that was approved by an Institutional Review Board at each participating site. The study was conducted in accordance with the Declaration of Helsinki and all applicable regulations. Details of the study methods have been reported elsewhere.11in situ less than 2 cm in diameter. Most patients were postmenopausal Caucasian women with no family history of cancer. Each patient was implanted with an appropriately‐sized Axxent balloon applicator  based on the size and shape of their tumor cavity. After implantation, the balloon was inflated with sterile saline to an optimum size as evaluated by computed tomography (CT) imaging. The CT images of the implanted balloon were used for developing both the eBx and the Ir‐192 treatment plans using BrachyVision  treatment planning system (TPS) or Plato TPS . The TG‐43U method for modeling brachytherapy dose distribution was used to compute dose distributions for both the eBx source and Ir‐192. The TG‐43U model assumes a uniform water scattering media, and while it may not fully describe the dosimetry, it was chosen for this study as it was the most commonly available commercial model at the time. The prescription dose was 3.4 Gy per fraction for 10 fractions to be delivered to planning target volume (PTV) that covers the volume 1.0 cm beyond the balloon surface.Patients selected in this study were greater than 50 years old with completely resected T1 invasive ductal cancer or ductal carcinoma d Ir‐192.,13 TDose‐volume histogram (DVH) metrics were compared between eBx and Ir‐192 treatment plans. The dosimetric data in this report includes the percent of the PTV receiving 90%, 100%, 150%, 200% and 300% of the prescribed dose as shown in Fig. The correlation of total nominal dwell times (TNDT) required for the planned treatments using the eBx method with the balloon fill volume and PTV at implant time was studied. The TNDT is the summation of the dwell times at all planned dwell points.Comparisons of the DVH metrics show that the PTV coverage was similar between the two treatment modalities Table . There wR2=0.81 and The TNDT for each patient is shown for each reported balloon fill and PTV volumes in Figs. The thinner lines on each Figure represent the scaled linear fit, which encompasses at least 50% of the data points (inner pair) and at least 90% of the data points (outer pair). For this linear model, 50% of the data points are within 7% and 5% of the linear regression fit for the balloon fill and PTV volume, respectively, and 90% of the data points are within 13% of the fit for both comparisons. It is important to note that these equations for the TNDT correspond only to a prescribed dose of 3.4 Gy per fraction to the PTV. who compared the treatment plans of 15 patients treated with Ir‐192 for localized breast cancer with simulated eBx treatment plans for the same 15 patients. The analyses showed comparable target volume coverage with the two sources; however, the eBx treatment plan had an increased high‐dose region within the target volume, a decreased dose to normal tissue including the ipsilateral lung, and, for patients with tumors on the left side, a decreased dose to the heart. Similar reductions in dose to surrounding normal tissue were also seen with a later comparison of actual Ir‐192 treatment plans and simulated eBx plans for patients with endometrial cancer. Similarly, the PTV coverage was found comparable between the two sources, though the high‐dose regions within the PTV were increased and the normal tissue sparing was greater with eBx.The Axxent eBx system consists of a miniature electronic X‐ray source, a balloon applicator and a mobile controller. A flexible tungsten‐filled shield, Flexishield (Xoft Inc.), is often placed over the patient during radiation therapy to reduce ambient exposure to the patient and staff. The MammoSite Ir‐192 brachytherapy (IB) system consists of a balloon applicator and a high‐dose rate (HDR) Ir‐192 remote afterloader, which must be used in a shielded radiation vault. Both of these forms of APBI deliver a prescription dose of 3.4 Gy in 10 fractions over five days. The dose rate of the eBx source exceeds that of an HDR Ir‐192 source; however, the eBx source has lower photon energies and a much steeper dose fall‐off with distance. The increased normal tissue sparing as seen in the heart and lung statistics in this study is attributed to the rapid dose fall‐off of the eBx source. The present results are consistent with those reported by Dickler et al.,9 who Ir‐192 plans, it must be noted that the TG‐43U method does not accurately reflect the absorbed dose‐to‐bone at lower photon energies. The mean energy for the Axxent 50 kVp source ranges from 28–34 keV, similar to the photon energy of I‐125(28keV). The absorbed dose‐to‐bone compared to tissue is considerably higher at these energies, reportedly 4–5 times greater than the absorption in tissue. At least one study has investigated this effect of increased bone dose absorption for therapeutic brachytherapy using I‐125. This study reviewed 74 cases where I‐125 seeds were placed almost directly on bone . The authors in that study found that after one to four years of follow‐up, there was no radiographic evidence of osteoradionecrosis or excessive osseous toxicity. The authors noted that while the dose absorbed by the first 1–2 mm of bone may be very high, there was little dose that penetrated to the underlying marrow or bone layers. In Ir‐192 breast treatments, rib fractures have been reported in 2%–4% of cases. However, no clear correlation between dose and likelihood of fracture has been established. In the one‐year follow‐up of eBx APBI treatments, no rib fractures have yet been noted; however, longer follow‐up may be required to determine the risk of osteoradionecrosis. Additionally, larger %V150 and %V200s with interstitial brachytherapy have been associated with an increased risk of developing fat necrosis. A fat necrosis occurrence rate of 5.5% at one year following treatment with eBx has recently been reported. Longer follow‐up is needed to further assess the risk of fat necrosis in patients treated with eBx.Although the calculated maximum rib doses were similar between the eBx and energies.,13 T5×7 ellipsoidal balloon, which was filled to 93cm3, the lower end of the manufacturer's recommended limits (90–135cm3). However, the 399.0 second TNDT predicted by the 99.0cm3 PTV for this balloon was within 13% of the expected trend. A potential method for quality assessment of any given plan would be to verify that the TNDT falls within the 13% limits of either, or both, volume‐based metrics as described in Eq. Many factors can influence a final treatment plan including TPS accuracy and precision, acceptable dose volume histogram (DVH) coverage , the centering of the source channel in the implanted balloon, and nonspherical PTVs. It is not expected that a final plan could be generated from only the fill volume parameters. However, as 90% of the total nominal dwell times are within 13% of the linear regression of the balloon fill volume, the linear regression fit could be used as a quality metric to evaluate a plan. All TNDTs were within 13% of either the fill volume trend or the PTV trend. For example, in Fig. 10%–15% for Ir‐192. A similar scatter effect for skin dose may, or may not, be noticed for eBx. As techniques improve for modeling skin, lung and bone doses, a retrospective review of dosimetric results originally obtained using TG‐43U models will be useful to correlate the clinical results with the improved dosimetry.Recent advances in brachytherapy modeling which account for suboptimal scattering conditions at skin or lung boundaries will change this dosimetry. For example, skin doses are reportedly overestimated by as much as r Ir‐192.18 A sThis dosimetric comparison of Ir‐192 and eBx sources demonstrated that both forms of balloon‐based brachytherapy provide comparable dose to the PTV in the delivery of accelerated partial breast irradiation. EBx is associated with increased high‐dose areas within the PTV. The steeper dose fall‐off with the eBx source resulted in appreciably increased normal tissue sparing in the heart and ipsilateral lung. The long‐term effects of increased absorbed rib dose cannot be assessed at this time. A quality assurance metric incorporating the balloon fill and PTV volumes to check the total dwell time generated by the TPS has been proposed.The authors wish to thank all site participants and investigators who supported this research, and the patients and their families for participating in this study. Funding for this study was provided by Xoft, Inc.


The functional replacement of tendon represents an unmet clinical need in situations of tendon rupture, tendon grafting, and complex tendon reconstruction, as usually there is a finite source of healthy tendon to use as donors. The microfibrous architecture of tendon is critical to the function of tendon. This study investigates the use of electrospun poly(ɛ‐caprolactone) scaffolds as potential biomaterial substitutes for tendon grafts. We assessed the performance of two electrospinning manufacturers  and the effect of two sterilization techniques—gamma irradiation and ethanol submersion—on cell response to these electrospun scaffolds after their implantation into a murine tendon model. Cell infiltration and proliferation analyses were undertaken to determine the effect on cell response within the implant over a 6‐week period. Immunohistochemical analysis was performed to characterize inflammatory response and healing characteristics . Neither the sterilization techniques nor the manufacturer was observed to significantly affect the cell response to the scaffold. At each time point, cell response was similar to the autograft control. This suggests that ethanol submersion can be used for research purposes and that the scaffold can be easily reproduced by a large‐scale manufacturer. These results further imply that this electrospun scaffold may provide an alternative to autograft, thus eliminating the need for sourcing healthy tendon tissue from a secondary site. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 389–397, 2017. The effectiveness of autografts in the treatment of major tendon injuries is limited by the relative paucity of donor sites and tissue. Although autografts provide an excellent method of replacement, for large or neglected tendon injuries, supplementation with a tendon‐like material is often desirable.We have researched and developed an electrospun poly(ɛ‐caprolactone) (PCL) scaffold as a novel device intended to aid in tendon regeneration following the loss of tendon tissue.Before being approved for use in the human body, the PCL scaffold must be demonstrably sterile. As stated by Rogers, sterility can be described as “the complete removal or destruction of viable organisms”.A sterilization process may have a degenerative or a destructive effect on a product, creating a need to validate its functionality poststerilization. Common methods of medical product sterilization include ionizing radiation and, in research laboratory settings , alcohol sterilization.Ionizing radiation generally involves the use of beta (electron beam) or gamma radiation emitted by a radioactive isotope  to deliver a measurable dose range to the packaged product at room temperature. The radiation is highly penetrative and breaks down chromosomal DNA to inactivate microbes. As ionizing radiation is known to affect polymer properties, the product functionality must be validated at the maximum possible dose administered. Changes in the mechanical, surface, and thermal properties are observed in polyurethanes and depend on the initial polymer chemical structure.Alcohol sterilization involves completely submerging the product and soaking in a 70% (v/v) ethanol (or isopropanol [IPA]) solution for a minimum length of time; however, it is not a sterilization method approved by the regulatory bodies. The mode of action is postulated to be rapid protein denaturationFor the electrospun PCL scaffold, gamma irradiation has been shown to negatively affect the surface topography,in vivo. Furthermore, implanted scaffolds were manufactured at two separate sites to determine device transfer and scalability in the future.The aim of this article was to determine the effects of gamma and ethanol sterilization, as well as time, on the functionality of the PCL scaffold after their implantation 5 g/mol was used by two separate manufacturing sites—by an in‐house manufacturer, University of Manchester, UoM, and by an external manufacturer, The Stellenbosch Nanofiber Company (SNC)—to create electrospun PCL fiber scaffolds.Commercially available medical grade PCL  with molecular weight 1.2 × 10UoM scaffolds were prepared by electrospinning a 10%w/v solution of PCL dissolved in 1,1,1,3,3,3‐hexafluoroisopropanol  targeted toward an earthed thin‐edged mandrel  positioned at 20 cm from the end of the needle. The polymer solution was expelled from the end of the needle‐tipped syringe at 20 kV (applied voltage) and 1 mL/h (flow‐rate). Collected fibers were removed as a single ribbon and manually twisted into yarns —where partially aligned nanofibers were collected onto a rotating mandrel coated with foil (order number: PCL01yrn). The nanofibers were subsequently rinsed with 70%v/v ethanol (EtOH), followed by deionized water and rinsed again with 70%v/v EtOH before being left to dry at room temperature. SNC nanofibers sheets subsequently received at UoM were cut into thin ribbons (3 × 400 mm), where fiber alignment was parallel to the ribbon length, and manually twisted to create nanofibrous yarns.Twisted yarns were sterilized either by gamma irradiation  or by submerging them in increasing concentrations of EtOH (70–100% v/v), 12 h per concentration, followed by rinsing several times in sterile phosphate‐buffered saline (PBS). Ethanol sterilization and PBS washes were performed within a class II microbiological safety cabinet.in vivo study was conducted over a 6‐week period, with time points at 3 days, 3 weeks, and 6 weeks  at 8–10 weeks of age were anaesthetized by isoflurane  induction (4 L/min of oxygen with 4% isoflurane). Once induced, mice were maintained at 2 L/min oxygen with 2% isoflurane for the rest of the procedure. A tourniquet was applied securely to mice hind limbs, immobilized in blue tack with the palmar side facing up, and cleaned with an ethanol wipe. Under a Leica MZ7.5 operating microscope , a size‐11 scalpel blade was used to lacerate the epidermal layer of the limb to expose the flexor digitorum longus (FDL) tendon. Using forceps and Vannas Spring Scissors , a 3 × 1 mm segment of the FDL in the hindpaw of a mouse was resected. Yarns were then implanted and affixed by a single figure‐of‐eight suture  at either end. Tendon autografts were also performed in the opposite hindpaw using the excised tissue to act as positive controls. The wound was closed and sutured and the mice were left to recover from the surgery in individual cages. At the appropriate time point, mice were euthanized by complete dislocation of the neck and whole hindpaws were harvested for fixation.n = 4) at each time point (n = 3). Slides were scanned using a Pannoramic 250 Flash II digital slide scanner and images were saved to allow for analysis on the Pannoramic Viewer software. Additional odd tissue sections (n = 2) between the even H&E‐stained slides were stained with eight immunohistochemical markers , and placed on polysine slides and stained with hematoxylin and eosin (H&E). Four representative sections were taken from each sample (rs Table  for eachrs Table  were anaX) was further bisected [Fig. Y. The cell nearest to the midpoint was marked and using the distance measurement tool, the distance along X and Y were measured to give X1 and Y1, respectively.Cell infiltration into the implant area is an indicator of the efficacy of the scaffold in encouraging cellular attachment and migration. H&E‐stained sections were taken from the middle of the graft/tissue. In each case, the central implant location was determined by the position of the sutures, the greatest area of the graft and examining the cell and tissue orientation. Using the freeform annotation tool within the Pannoramic Viewer software, the implant area was marked and labeled. Using the measurement annotation tool, the area was bisected lengthways by eye and the resulting line  over the time period investigated.Cell coverage was analyzed to indicate the percentage of cells present within the implant area over time. Similar to that for cell infiltration, H&E‐stained sections were taken from the central location of the graft/tissue, which was determined by the position of the sutures, the greatest area of the graft and examining the cell and tissue orientation. H&E‐stained samples were analyzed using the HistoQuant module for Pannoramic Viewer. Using an example slide, a “mask” template file was created to automatically select all purple and blue areas  in the slide and calculate the exact area of these cells Fig.   and the tissue immediately surrounding the implant. Representative images were saved using Leica QWin analysis software.Results from all the three experiments were analyzed using a Kruskal–Wallis one‐way analysis of variance (ANOVA) (GraphPad Prism 6 software). Sample types were compared to the corresponding autograft control. Each set of results for a single sample type was also compared over time.X and dY, respectively).Results from cellular infiltration were analyzed and each sample type was compared to the corresponding autograft control at each of the three time points. Infiltration was measured along [ for the autograft cohort between 3 days and 6 weeks (p < 0.05).Statistical analysis demonstrated no significant difference between any of the samples and the autograft control for all time points. Similarly, there was no significant difference between any of the time points within each sample set, except for cells infiltrating along the length of the implant .Statistical analysis demonstrated no significant difference between any of the samples and the autograft control at any time point. Similarly, there was no significant difference between any of the time points within each sample set, except for between 3‐day and 3‐week results for the UoM Ethanol scaffold  concluded that gamma irradiation of electrospun PCL scaffolds led to improved cellular attachment and growth, and that a dose of 35 kGy can sufficiently sterilize the scaffold “without compromising the materials properties” or cell proliferation. concludein vivo murine study has demonstrated this not to be indicative of implant encapsulation, and PCL scaffolds positively encouraged collagen deposition compared to autograft controls over this time period.Immunohistochemical analysis of eight antibody markers was undertaken to analyze the extent of implant acceptance, inflammatory response  and cell proliferation (BrdU), death (TUNEL), and collagen synthesis (Hsp47) into the implant area. Ideally, high levels of matrix deposition, collagen production, cellular proliferation, and the presence of α‐smooth muscle actin (SMA) as a sign of cellular contraction would indicate the onset of tendon assembly. SMA has been identified in tenocytes during critical phases of tendon healing.In general, there was no significant difference observed for any of the sample types at any time point for any of the markers analyzed. The density of CD45 (an inflammatory marker) was slightly higher across all time points for all SNC and UoM samples, except two—SNC 6‐week implant area and UoM 3‐week surrounding area. This indicates elevated levels of inflammation for these samples compared to the autograft control. However, this is expected as synthetic polymers are known to illicit an early inflammatory response as the immune system reacts to the presence of a foreign body.Overall, no significant difference in cell biological expression markers was observed between any of the scaffolds and the autograft gold standard, suggesting that these scaffolds may offer an alternative intervention for tendon repair.in vivo studies are required, but our electrospun PCL scaffold offers promise to becoming an alternative intervention for patients requiring tendon repair.The sterilized electrospun PCL scaffold functioned similarly to the gold standard autograft control in terms of cell response over a 6‐week time period. Neither ethanol nor gamma sterilization had an observable effect on the functionality of the scaffold when compared to the autograft control. The manufacturer of the electrospun PCL fibers did not have an effect on the performance of the scaffold, which would allow the manufacturing process to be easily outsourced and scaled up for commercial translation. Further long‐term


RNAs of bone‐derived exosomes involved in the regulation of bone remodelling, as well as the potential clinical applications of bone‐derived exosomes in bone remodelling disorders.Pathological destructive bone diseases are primarily caused by the failure of a lifelong self‐renewal process of the skeletal system called bone remodelling. The mechanisms underlying this process include enhanced osteoclast activity and decreased generation of the osteoblast lineage. Intercellular interaction and crosstalk among these cell types are crucial for the maintenance of bone remodelling, either through the secretion of growth factors or direct cell–cell physical engagement. Recent studies have revealed that exosomes derived from bone cells, including osteoclasts, osteoblasts and their precursors, play pivotal roles on bone remodelling by transferring biologically active molecules to target cells, especially in the processes of osteoclast and osteoblast differentiation. Here, we review the contents of bone‐derived exosomes and their functions in the regulatory processes of differentiation and communication of osteoclasts and osteoblasts. In addition, we highlight the characteristics of micro Pathological destructive bone diseases via direct physical interactions, such as the engagement of ephrin/Eph receptors Bone remodelling, which takes place in the bone remodelling compartment, is a continuous and lifelong process of repair of micro‐damage to the bone structure and the replacement of ageing bone tissue Various types of cells, such as epithelial and haematopoietic cells, secrete exosomes. The latest studies have demonstrated that bone‐related cells, including osteoclast precursors, osteoclasts, MSCs, osteoblasts and osteocytes, also secrete exosomes via the transfer of critical molecules required for the differentiation and communication of osteoclasts and osteoblasts Accumulating evidence supports the endocrine function of the skeleton The contents of exosomes vary according to their origin. To provide a better understanding of the mechanisms by which bone‐derived exosomes regulate bone remodelling, we have reviewed the latest discoveries regarding the changing characteristics and roles of bone‐derived exosomes during the regulation of osteoclast and osteoblast differentiation. Furthermore, we highlight the characteristics of bone‐derived exosomal microRNAs involved in regulation of bone remodelling as well as the potential clinical applications of bone‐derived exosomes in bone remodelling disorders.et al. et al. Although the processes by which bioactive molecules are packaged into exosomes are largely unknown, recent reports suggest the existence of a specific and tightly controlled mechanism Similar to the function of cytokines and soluble factors, bone‐derived exosomes can recruit BM‐derived cells, such as HSCs (precursors of osteoclasts) and MSCs (precursors of osteoblasts), to the bone surface et al. et al. and Ekstrom et al. indicated that exosomes secreted from monocytes, which are derived from HSCs and share precursors with osteoclasts, stimulated the osteogenic differentiation of MSCs et al. and Sun et al. demonstrated a novel models of inhibitory effect on osteogenic differentiation by osteoclast‐derived miR‐214‐containing exosomes The roles of exosomes in osteoclasts may provide clues as to how bone formation and absorption are orchestrated Matrix vesicles (MVs), known to be important in the development of vertebrate mineralizing tissue, share structures that are homologous to those that anchor exosomes to the ECM as well as similarities in morphological appearance and functional activities The function of exosomal miRNAs has become a focus of research because of their pivotal role in gene expression regulation. microRNAs are small endogenous non‐coding RNA molecules, containing approximately 22 nucleotides. They are well known as post‐transcriptional regulators of messenger RNA (mRNA) expression Recent research has revealed the involvement of a number of bone‐derived exosomal miRNAs in the regulation of bone remodelling Table . Forty‐tvia the Wnt signalling pathway. AXIN1 expression was repressed and β‐catenin expression was enhanced after transfer of mineralized osteoblast exosomes, thereby promoting the osteogenic differentiation of precursors of osteoblasts In addition, osteoblastic differentiation‐related miRNAs are greatly increased in mineralizing osteogenic ST2 cells, with 91 up‐regulated and 182 down‐regulated after coculture with mineralized osteoblast‐derived exosomes. Among the 91 overexpressed miRNAs, 18 were contained in mineralized osteoblast‐derived exosomes, including four highly expressed miRNAs . Only 20% of miRNAs overexpressed in recipient cells were detected in exosomes from original osteoblasts, suggesting that the transfer of exosomal miRNAs only contributes partly to the altered miRNA expression in recipient cells, and other mechanisms that modulate the miRNA expression of recipient cells might be existed. Among the miRNAs overexpressed in recipient cells, five up‐regulated miRNAs  cotarget AXIN1, which is a key β‐catenin inhibitor. β‐catenin is an essential transcription factor involved in osteoblast differentiation RUNX2 gene, were highly expressed in osteoblast‐derived exosomes Let‐7, which is found in exosomes from both mineralized osteoblasts and osteoblast precursors, was shown to enhance osteogenesis by regulating high‐mobility group AT‐hook 2 (HMGA2) and AXIN2 MAFB gene et al. showed that elevated serum exosomal miR‐214‐3p is associated with reduced bone formation in both elderly women and ovariectomized (OVX) mice via ephrinA2/EphA2 et al. ATF4, while their further experiments identified that miR‐214 promotes osteoclastogenesis through PI3K/Akt pathway by targeting the Pten tensin homologue via mechanisms such as paracrine/autocrine signalling or in communication between osteoclasts and osteoblasts or with other cell types As communicators in bone remodelling, exosomes derived from the osteoblast lineage contain miRNAs that target key osteoclast differentiation factors. miR‐503‐3p from mineralized osteoblast‐derived exosomes may inhibit RANKL‐induced osteoclast differentiation by regulating RANK expression Here, a new aspect of the roles of bone‐derived exosomes in bone remodelling has been elucidated. The content of bone‐derived exosomes, including the proteins, mRNAs and miRNAs, varies according to different parent cells. Therefore, bone‐derived exosomes exert multiple roles in bone remodelling Fig. . ExosomeSOST gene) to inhibit the activity of osteoclasts and osteoblasts Bone‐derived exosomal miRNAs are thought to be important in regulating gene expression involved in the differentiation and communication between multiple cell types responsible for bone formation and resorption. Recent studies have shown that Wnt5a enhances osteoclast formation through β‐catenin‐dependent signalling The cargo of tumour‐derived exosomes vary according to the cancer types and tumour characteristics All co‐authors implicated in this review declare that they have no conflict of interest.


This paper reports on the methodology and materials used to construct anthropomorphic phantoms for use in dosimetry studies, improving on methods and materials previously described by Jones et al. . To date, the methodology described has been successfully used to create a series of three different adult phantoms at the University of Florida (UF). All phantoms were constructed in 5 mm transverse slices using materials designed to mimic human tissue at diagnostic photon energies: soft tissue‐equivalent substitute (STES), lung tissue‐equivalent substitute (LTES), and bone tissue‐equivalent substitute (BTES). While the formulation for BTES remains unchanged from the previous epoxy resin compound developed by Jones et al. , both the STES and LTES were redesigned utilizing a urethane‐based compound which forms a pliable tissue‐equivalent material. These urethane‐based materials were chosen in part for improved phantom durability and easier accommodation of real‐time dosimeters. The production process has also been streamlined with the use of an automated machining system to create molds for the phantom slices from bitmap images based on the original segmented computed tomography (CT) datasets. Information regarding the new tissue‐equivalent materials, as well as images of the construction process and completed phantom, are included.PACS number: 87.53.Bn This is especially useful considering the increasing use of proprietary scanning techniques that are difficult to model, such as automatic tube current modulation in CT and automatic exposure control (AEC) in fluoroscopy. The majority of organ dose studies in diagnostic imaging utilize commercially available anthropomorphic phantoms such as RANDO  or ATOM phantoms . In order to provide a representation of the human anatomy, these commercially available phantoms typically use three tissue equivalent materials imitating bone, lung, and soft tissue. To allow access to organ locations for the placement of dosimeters, the RANDO and ATOM phantoms are assembled in axial slices 2.5 cm thick. Unfortunately, the widespread clinical use of these phantoms has been limited by their prohibitive costs.Anthropomorphic phantoms constructed from tissue‐equivalent materials have historically been used to provide a physical representation of the body's anatomy and attenuation characteristics for radiation dosimetry studies. Of particular interest for this publication is the use of anthropomorphic phantoms for measuring dose in diagnostic imaging procedures, where such measurements have been used by several authors to calculate average organ doses as well as effective dose in computed tomography (CT), cone‐beam CT, and pediatric radiology.–3 Qu and later improved upon by Jones et al.,The University of Florida (UF) has recently developed a series of low‐cost tissue‐equivalent materials that are easily prepared in the laboratory, and incorporated them in several sophisticated anthropomorphic phantoms. To date, this process has been used to create a series of three adult phantoms. Expanding upon methods originally published by White et al.,,5 anThe advantages of the UF phantoms compared to commercially available phantoms are that they utilize a 5 mm slice thickness, allowing greater options for dosimeter placement when performing internal dose measurements, and the anatomy is precisely known with respect to the CT data set used to construct the phantom. In addition, each physical phantom has a corresponding segmented computational phantom that was created from the same original CT data set, such as those developed by Lee et al.The full‐body data set includes over three hundred axial slices; however, the lack of radiosensitive organs in the legs justified their exclusion from fabrication. As such, each phantom includes approximately two hundred axial slices, ranging from the crown of the head to mid‐thigh. All internal organs in the phantoms are modeled as soft tissue and, therefore, dosimeter placement for organ dose measurements is based solely on position of the segmented organs in the original data set. To aid in dosimeter placement, organ locations have been transferred onto each slice from full‐scale printouts of the original segmented data set.The tissue‐equivalent substitutes used for this undertaking were developed with two goals in mind: 1) similar physical properties to human tissue, such as density and attenuation coefficients, and 2) ease of integration into the phantom manufacturing process. To meet these goals, new urethane‐based STES and LTES were developed.2.The developed tissue‐equivalent materials were evaluated by measuring the material density and attenuation properties. The attenuation coefficient of the STES was evaluated by measuring the attenuation from multiple thicknesses of material using a narrow beam geometry generated by clinical radiographic unit. Additionally the Hounsfield Unit (HU) values were measured in the completed phantom using a Siemens Somatom Sensation 16‐slice CT scanner operated at a tube voltage of 120 kVp and employing an mA modulated exposure control. The average HU was determined from the selected regions of interest (ROI) using areas of approximately 10 cmmdry, of each sample. The samples were then weighed submerged in a beaker of de‐ionized water to find the wet mass, mwet, of each sample. Using both these measurements, as well as the known density of the de‐ionized water, ρH2O, the density of each sample was calculated using Eq. Density measurements of each sample were then taken utilizing Archimedes's principle. A cured sample of each material was weighed on a scale with 0.001 gram precision to find the dry mass, (1.04g/cm3) and to achieve a target X‐ray attenuation coefficient based on the ICRU‐44 reference soft tissue composition. The commercially available, two‐part urethane rubber compound “PMC 121/30 Dry”, , was combined with 2.8% by weight of powdered CaCO3  to achieve these design goals. The calcium carbonate was added to the two parts of urethane and mixed with an electric mixer, with care being taken to ensure a homogeneous mixture with no undissolved CaCO3. The durable, readily available urethane‐based compound was found to be easy to work with and did not suffer from phase separation problems frequently encountered with epoxy resin based STES. An additional benefit of the urethane‐based STES is its filexibility, which allows easy removal from molds after curing.A new urethane‐based STES was designed to match the X‐ray attenuation and density of human soft tissue within the diagnostic energy range (80–120 kVp). Specifically, the STES was designed to have a density similar to that of human soft tissue position.,10 TAdipose tissue was not specifically modeled in the construction of the anthropomorphic phantom. The distribution of subcutaneous as well as intra‐abdominal adipose tissue was initially determined to be too complicated to directly model with a specific tissue‐equivalent material. Thus, the STES was developed to be a homogeneous soft tissue analog that comprises skeletal muscle as well as organs, connective tissue, and adipose tissue.0.33g/cm3 was chosen for the LTES, representing the density of a fully inspired lung.Anew LTES was designed by combining uncured urethane‐based STES, prepared as described above, along with poly‐fil polystyrene micro beads  in a 10:1 ratio by weight. This LTES is very uniform and permits the fabrication of a range of tissue densities spanning various levels of inspiration. Since it does not rely on a tissue surfactant and foaming agent, the LTES is more uniform and reproducible than the method proposed by White et al.(μen/ρ) for those defined by the Oak Ridge National Laboratory (ORNL) stylized model seriesμen/ρ for BTES had a maximum deviation from ORNL reference values of only a few percent.The BTES used was the epoxy resin based material previously developed by Jones et al.Initially, the methodology described by Jones et al. The original tomographic data for each hybrid phantom came from a 36‐year‐old Korean adult male  and 25‐year‐old adult female . The adult male exam was performed as part of a cancer screening protocol using a Siemens Somatom Emotion Duo PET/CT system with a slice resolution of 3 mm. The adult female was performed with a 4.5 mm slice resolution. All scans were performed at full inspiration with an in‐plane matrix size of 512×512pixels. Organ segmentation was performed manually under supervision of a radiologist. While approximately 100 different tissues were segmented in the computational data set, only the organs needed for the calculation of effective dose, as outlined in ICRP 103,As previously mentioned, three different phantoms have been constructed to date. The first phantom was based on a 35‐year‐old Korean adult male, 172 cm in height and 68 kg in total body weight.,16 TThe first step in constructing the phantom was to convert the segmented data set into a form that could ultimately be read with the automated machining software. Using ImageJ software , each segmented image was converted into a bitmap representing only soft tissue and other tissues . This was accomplished by segmenting bone, lung, and air to a single pixel value representing “voids,” while all remaining soft tissues were shaded with another single value representing soft tissue. Registration marks for assisting in phantom assembly and alignment were also added to each bitmap image and the finished bitmaps were then imported into the VisionPro software. Each bitmap was adjusted to conform to the 256 value color range in the VisionPro software and vectorized in order to smooth the pixilated edges of the digital images. A speckle filter was used to eliminate tissue islands less than four pixels in area. Once these steps were complete, engraving paths for all areas represented by the soft tissue pixel value were then created for each slice. Realizing that smaller diameter “end mill” bits allow finer details to be cut, a 1/8‐inch diameter bit was selected for body engraving paths while a 1/16‐inch diameter bit was chosen for engraving paths in more detailed regions of the head.The engraving paths were used to mill soft tissue molds in a high‐density foam, which could then be filled with the soft tissue substitute. Foam blanks were fastened to the engraving table and single‐pass engraving paths were set with depths resulting in 5 mm thick soft tissue slices. To create clean edges in each foam mold, a perimeter engraving path was first performed at a slow feed (0.6” per second), outlining the entire perimeter of the area to be cut. This was followed by a much faster rate fill engraving path (3” per second), which removed all foam material within the perimeter engraving path. Molds for each slice could be created in approximately ten minutes. The process of manufacturing a soft tissue mold is shown in Fig. After engraving was completed, the molds were checked to ensure that all areas to be filled with STES were connected, to aid in future placement. In cases where an area to be filled with STES was surrounded by bone or lung, small grooves were cut in the mold with a razor blade in order to connect the soft tissue island to the main body of the slice. This is similar to a stencil where the center of the letter “O” must be joined with thin connectors to ensure proper orientation. Finally, the job time for each slice was recorded. The job time and feed rate were used to determine the approximate volume/weight of soft tissue‐equivalent material needed for each slice.Depending on how many soft tissue molds were being filled at a time, an appropriate amount of the urethane‐based STES was mixed and immediately poured into the soft tissue molds. This was done fairly rapidly (less than 30 minutes), as the STES began setting immediately. The filled molds were covered with waxed paper and any trapped air pockets were relieved by slicing the waxed paper with a razor blade. The molds were then covered with smooth, weighted boards in order to force excess STES out of the molds, which would allow the soft tissue slices to cure at the correct thickness (5 mm). After roughly three hours, the weight and waxed paper were removed from the partially cured soft tissue slices. It is important to remove the waxed paper prior to the STES fully curing in order to facilitate removal. After 24 hours, the soft tissue slice could be removed from the mold and any excess STES around the edges was trimmed with a razor blade.For images that included lung tissue, separate molds were created in a similar fashion to the soft tissue molds described above, in order to produce lung inserts for the phantom. Unlike the STES, the LTES is not fluid and must be spread into the lung molds. As with STES introduction, waxed paper along with smooth, weighted boards were used to ensure that the LTES inserts were uniform in thickness. The LTES is not as strong as the STES and did not remove as easily from the foam molds, requiring that the molds be cut away from the newly formed lung slices. These slices, which were an exact fit to the corresponding voids in the soft tissue slice, were then fixed to the soft tissue slice with the introduction of the BTES into rib locations.The method of placing bone into the soft tissue slices was analogous to that of Jones et al.Once all the phantom slices were completed, the organs and locations of dosimetric importance were selected. Full‐scale printouts of the segmented images containing these measurement locations were used to trace and label the organs of interest onto the physical phantom slice using a permanent marker. Additionally, phantom slices containing these locations were left unattached to a bordering slice in order to allow access for dosimeter insertion. All other slices were bonded to adjacent slices using commercially available wood glue. The glue was placed uniformly over all areas of a slice surface with the exception of air spaces and LTES. Wood glue has been found to behave radiologically similar to soft tissue at diagnostic energies.1.04g/cm3. The average HU for the STES material was found to be 9.8, at the lower end of the widely accepted range for human muscle (10–40 HU). However, the measured value is considered acceptable because STES represents a homogenized mixture of both muscle and adipose tissue, with the latter having a HU range of −50 to −100.The STES was empirically evaluated using an X‐ray source (3.9 mm Al HVL at 80 kVp) to have an HVL of 25 mm at 80 kVp, and 29 mm at 120 kVp. The measured density was 0.33g/cm3, agreeing with the targeted lung density for full inspiration. The average HU for the LTES material is −678.4, consistent with widely accepted HU values for lung, which range from −500 to −1000.The density of the LTES was measured to be The BTES has been previously characterizedTo date, three adult phantoms have been created using the methods and materials described in the previous section. As previously mentioned, the first phantom created, shown in Fig. Figure The urethane‐based STES has numerous advantages over the epoxy resin based soft tissue substitute originally proposed by Jones et al.Creating molds resulting in uniform 5 mm thick phantom slices proved more challenging than expected. Small variations in individual slice thickness can accumulate to create large discrepancies when hundreds of slices are combined. Early on, molds would occasionally display a variation in cutting depth throughout the slice. The engraving system hardware and software was initially suspected and investigated. However, it was found that this variation in cutting depth was the result of the foam template bowing upwards and losing adhesion to the engraving table during the milling process. Similarly problematic, engraving path depths were also initially set to the desired 5 mm, which was expected to result in a 5 mm thick soft tissue slice. However, the excess freshly poured STES could not be pressed infinitely thin, and so an additional thickness of 0.5–1 mm would often result. Thicknesses of this magnitude, reflexively considered minor, are in fact considerable with respect to 5 mm thick slices, resulting in slices that were 10%–20% too thick. This problem was corrected by adjusting the indicated engraving depth to 4 mm and using a consistent procedure to define the cutting surface to the engraving system.A unique methodology has been developed to construct anthropomorphic phantoms for use in dosimetry studies. While the value of this methodology has already been proven with the construction of three adult phantoms, it should be noted that the same methodology could be applied to the construction of phantoms of all sizes and ages. In particular, our group plans to develop a family of phantoms that accurately represent patients of differing heights and weights. Future works also include the investigation of an adipose tissue‐equivalent substitute which could be added to the existing phantoms – or included as an additional step in the construction of a new phantom – to represent subcutaneous fat, in order to accurately model more obese patients.While anthropomorphic phantoms have many potential applications, this particular phantom series was created to quantify organ doses from diagnostic procedures. It is anticipated that other institutions could create their own phantoms for regular clinical use by following the methodology and using the described tissue equivalent materials for a total material cost of less than $3,500.This work was supported by the U.S. Department of Energy under project award number DE‐GF07–05ID14700, and the Center for Disease Control through TKC Integration Services TO81.