Shape memory alloys (SMAs) have found widespread applications as biomedical devices. Biocompatibility, corrosion resistance, and ductility make these alloys attractive for medical devices such as stents and filters. For these implants, the superelastic property is the primary function of SMAs. Additionally, these alloys, such as NiTi as the prime example, can be used for actuation. Several modes of actuation such as displacement control, force control, and compliance control have been used as harnesses with SMA devices. These two unique properties have opened another application in the form of neurosurgery and robot-assisted surgery devices, as well as controlled assistive and rehabilitation devices. This paper reviews the state of the art of application of SMAs in the latter category where control is applied to harness innovative medical devices. To this end, two major subsets of these devices: prosthesis and orthosis which take the advantage of SMAs in assistive and rehabilitation devices are studied. These devices are further categorized to hand prosthetics, elbow, knee and ankle orthotics. In most of these designs, SMA wires act as artificial muscles to mimic the motion of limbs in the target joints. The evolution of each category is explained, and the specific results of them are reported. The paper also reviews the SMA applications for neurological and neuromuscular rehabilitation. To this end, different categories of rehabilitation devices as a passive and aided exercise for the ankle, knee, and elbow are highlighted. The SMA actuator in these devices can be EMG-controlled to improved patient outcome. In addition to providing a comprehensive overview of the biomedical devices, this paper identifies several possible future directions of SMA related research in the area of assistive and rehabilitation devices. Shape memory alloys (SMAs) are the metallic materials that have the ability to return to some previously defined shape when they are subjected to the appropriate thermo-mechanical loading. The shape memory effect occurs due to the temperature and the stress-dependent shift in the materials crystalline structure between two different phases called Austenite (parent) and Martensite (product). Martensite, the low-temperature phase, is relatively soft whereas Austenite, the high-temperature phase, is relatively stiff. This change in stiffness is a key enabler in realizing SMA assistive and rehabilitation devices. Changing in the SMAs crystalline structure is not a thermodynamically reversible process and results in temperature hysteresis . The hysSMAs are currently used in a wide variety of applications such as architecture , aerospaStill, the high ductility and high reactivity of this alloy make it hard to build parts with more complex shapes and geometries hence hindering many SMA applications as actuators. Additive manufacturing (AM) methods such as selective laser melting (SLM) and direct metal deposition (DMD) are the very recent breakthroughs in fabricating metallic parts which enable the researchers to produce complex, functional, and ready-to-use parts from a computer-aided design model . FortunaSome key features which are discussed earlier, make the SMAs  an ideal choice in biomedical applications . TherefoAccording to the high variety of SMA applications in the biomedical domain, this paper studies the biomedical applications of the SMA (NiTi) in two main subsets: the assistive and the rehabilitation devices. The category shown in Prosthesis is an artificial substitute or replacement of a part of the body which enables people to do their daily activity normally. For example, lower limb prostheses enable a person with limb loss to walk, or a hand prosthesis helps the user to pick up things and lots of more functions that will eventually enhance the lifestyle of disabled people. As mentioned, the main problem of assistive devices such as prostheses is their actuation systems . ConsequThe Hitachi Hand was one of the first industrial hands and the most famous one that used SMA wires as artificial muscles . Y. NakaK. Laurentis and C. Mavroidis  imitatedThe anthropomorphic prosthetic hand developed by K. Andrianesis and A. Tzes ,21 is anAs a modification to this work, compression springs were added to the fingers to provide a powerless adaptive grip b. FurtheBesides, the resistance feedback control was utilized for position controlling of the fingers. In their most recent work , force sMoreover, it had the advantages of low cost of SMA wires as actuators, decreasing the cost of additive manufacturing, using the self-sensing capabilities of the SMAs for controlling purposes, and typical usage of 50 W power . Hence, H. Taniguchi designed a prosthetic hand for children by utilizing SMA actuators as the drive source to achieve a small size, silent operation, high output power, and low mass device ,25. To oJae H. Lee et al. firstly designed a prosthetic finger based on the human hand structure and then developed it to the five-finger prosthetic hand ,27. EachOrthosis is an artificial external device providing support and making alignment for the movable parts of the body to correct deformities or to improve the functionality of the relative movement. Orthotic devices are designed in a way to assist the impaired limbs partially or totally lost their power. Having a high energy density, light weight, and stimulating by heating are some of the SMA properties that make these materials favorable for orthotic applications.Pittaccio et al. were among the first groups that investigated the potentiality of using superelastic NiTi in a compliant brace (EDGES) promoting spastic elbow relaxation . Their hSeveral special designed bending tests were conducted to find an appropriate moment-angle characteristic. To show the torsion behavior of the wires in superelastic mode, an aluminum structure was designed for mounting the prototype and applying the torque a. BeforeTwo post-stroke subjects wore EDGES for one week, at least 10 h per day. No additional treatment was applied during this period or the following week. An improvement (20° ± 5°) of the resting position was observed in both patients as early as 3 h after starting the treatment. As shown in The angle oscillation of flexion in In another study ,33, PittIn this study, the effect of thermal treatment on the superelastic alloys was considered to evaluate the changes on the torque-angle characteristics of the hinge. After evaluating the stability of the hinge for 20–100 cycles, the pseudoelastic hinge was used in a repositioning splint equipped, and the device was prescribed to the individuals with mild to severe spastic tetraparesis for the clinical evaluations . The subResults on rigidity change for the sole elbow joints were not significant for either pseudoelastic treatment  or traditional splints . A potential reason for why differences between pre- and post-treatment values of rigidity were not significant for the elbow joints may depend on the size of the corresponding population. It’s not possible to make a reasonable decision based on the limited data obtained from only five candidates.By analyzing the curves of Based on the results obtained from the clinical evaluation of the patients, the pseudoelastic therapy appeared to outperform the traditional one in that it was able to conserve or improve joint viscoelastic characteristics, while the traditional treatment could not prevent stiffening.Copaci et al. designed a wearable elbow exoskeleton actuated with Shape Memory Alloy in the antagonist movement ,35. TheiIn this study, the modified SMA based actuator consists of four wires of Shape Memory Alloy (SMA) inserted in one Bowden cable for the flexion movement and for the extension using the force of a torsion spring placed in the elbow exoskeleton joint. This modified configuration has a lower power consumption, offers a quick response, is more compact design, and can create more range of motion in comparison to the conventional devices which use DC and AC motor, hydraulic, and pneumatic actuators. The proposed elbow exoskeleton presents a lightweight, noiseless operation and can be built as a low-cost rehabilitation device by using a 3D printer and low-cost electronics and actuators.They developed a wearable prototype with three degrees of freedom which facilitates robotic-assisted in-home rehabilitation therapy . The proThe controller of the system provides reasonable results in tracking sinusoidal trajectories. The theory of stiffness control in differential configuration was also implemented. Miniature fans were utilized to increase the cooling rate and decrease the response time of the system.Knee ankle foot orthoses (KAFOs) are prescribed to improve abnormal ambulation of the knee caused by quadriceps weakness. There are three major types of KAFOs: passive KAFOs, stance control KAFOs, and dynamic KAFOs. The passive KAFOs fix the knee joint in the full extension position all the time. Such devices provide enough support but cause stiff walking patterns. Some other types allow free knee motions inversely, producing limited stability . PassiveThe stance control KAFOs prohibits knee movements in the stance while allowing free rotation at the knee in the swing . They geDynamic KAFOs are the only type capable of controlling the knee motions throughout the entire walking gait cycle. However, those available in the market are heavy, bulky, and have limited functionality . To addrFeng et al. ,44,45 weFor a better understanding, Ankle-foot orthoses (AFOs) are prescribed to assist the patients in achieving a more natural gait and to prevent muscle atrophy. Due to the high power to weight ratio, the SMA AFOs are lighter and have a simpler design in comparison to most of the conventional AFOs in the market which are more likely to be heavy, bulky, and to have a limited functionality. To address these issues, Bhadane et al. ,48,49, DBhadane et al. proposed novel active AFO which used superelastic wires ,48,49. AIn Comparing dynamic KAFO  and the SMA wire-driven AFO  shows SMA components can be designed for KAFOs and AFOs to create more normal knee and ankle angle and moments to create a normal gate. As seen in Deberg et al. designed and evaluated a passive AFO utilizing the superelastic behavior of the SMA wires ,51. The In another study, Mataee et al. presented two innovative SMA based adaptive solutions for the AFO mechanism based on the adjusting stiffness in bending and torsion ,53. The For the adjustable superelastic tube, the ankle stiffness of the AFO (simulation) and that of the healthy subject was plotted in Similarly, for the adjustable hinge concept, the stiffness profiles of the AFO (simulation) and that of the healthy subject were plotted in In another study, Amerinatanzi et al. developed an AFO that helps patients to have more normal ankle joint behavior . The proThe misalignment of the bones of the big toe is one of the reasons for creating the abnormal gate. The deformity may be in the digits of the hand, foot or other parts like the spinal skeleton. To solve this problem, some braces have been utilized to be fastened to the abnormal part to correct the abnormality . The trePalmer et al. invented a novel superelastic NiTi orthosis that maximizes the ability to slowly correct toe deformities  for neurology and neuromuscular rehabilitation . In thisThe moving plate consists of a shape memory actuator and two pseudoelastic bias springs. The actuator is activated cyclically and can create 30 degrees dorsiflexion in the patient’s ankle, while the bias springs reset the position in the plantar flexion. The Toe-Up device has been utilized by seven pediatric patients affected by spastic tetraparesis for 30 min in a day for 14 continues days, and initial results indicate that Toe-Up device has an acceptable effect on these patients.Another rehabilitation device which has been designed and built in this study is a kind of active device that consists of an EMG sensor and an SMA actuator. Designing a pseudoelastic hinge prototype by using an SMA spring is another example of a rehabilitation device that has been designed in this study. Pittaccio et al.  used an A rotary SMA actuator is another example of a rehabilitation device that has been designed in this study. Krishnan et al.  utilizedThe experimental set up for the SMA actuated Stewart platform rehabilitation device is shown in Regarding prosthetic hands, there are different parameters that severely restrict the range of use of the prosthesis. These parameters could be weight, DOF, the maximum applied force, or fabrication methods. These parameters can be classified for the abovementioned hands in SMA wires need time to be cooled; hence the cooling rate greatly affects the efficiency of these type of actuation. There have been different methods like using forced cooling mechanisms or metallic heat sinks to improve the efficiency of the cooling. However, it should be noted that adding these items can influence the controlling issues as well as increasing weight and the need for space. One of the most difficulties of employing SMA as an actuator is its control complexity. Large temperature hysteresis, nonlinearities, lack of a reliable feedback signal due to changing SMA parameters are some of the parameters that make it hard to control this device. Many papers have been published on the SMA control methods that can address this issue and applying these methods on prosthesis hands can improve position and force control of these devices. For example, position control and stiffness control methods using strategies like nonlinear or adaptive controls, have been employed to control SMA-based actuators. Due to the lack of an accurate model for SMA based actuators and the presence of various uncertainties in the considered model, some researchers prefer to use non-model-based control methods ,63. The Another interesting field of research that can be conducted for enhancing the hand prosthesis performance is to investigate the benefit of employing different kinds of SMA shapes like SMA springs or a bundle of wires. Also, a parametric study is needed on the length, diameter and the transformation temperature of SMA wires and their effect on the actuator performance.Recent research has shown that shape memory alloys can be one of the most promising actuators. Low cost, noiseless operation, light weight, high power-mass ratio and simple actuation make SMAs interesting alloys to be utilized as actuators. However, there are several disadvantages compared to the current advance commercial devices, and to the authors’ knowledge there are no commercial prosthetic hands in the market using SMA as an actuator. Some of the problems that hinder commercialization can be summarized as follows.So far, only one group has investigated the use of the dynamic knee actuating system for KAFO to improve abnormal ambulation of the knee caused by quadriceps weakness. Although the proposed KAFO has improved the stiffness profile when compared to the locked mode, still there is a large deviation between the dynamic mode and the normal behavior that needs to be addressed via further optimization of the KAFO. Also, the KAFO is super bulky due to the complicated actuation system, which makes it impossible for the patient to wear it. Possible future research on the topic of KAFOs will investigate: (i) improving and optimizing the mechanisms in order to make the KAFOs be more user-friendly, and have lower weight and volume; (ii) developing the KAFOs being able to accommodate more walking conditions, such as climbing stair, different walking speeds, and uneven grounds, and (iii) developing the passive KAFOs via taking advantage of superelasticity behavior of SMAs, such as the use of superelastic SMA based hinge, since it significantly reduces the complexity and volume of the device.Different groups have investigated the use of AFOs to assist the patients in achieving a more natural gait and to prevent muscle atrophy. In these devices, the purpose was to increase the applied moment, provide normal ankle stiffness, enhance the range of ankle motion, and provide dorsiflexion at the end of the swing phase. In the work presented by Bhadane et al., the required characteristics of the SMA wires were calculated via conducting experiments on a hinged AFO without any wires and measuring the deviation from the healthy subjects. However, after mounting the appropriate SMA wires on the system, the modified device performance was not compared to the results of normal subjects. Taking advantage of this concept, Deberg et al. considered an actuation system to tune the walking by employing a pulley and SMA wires system. The ankle motion was significantly enhanced for the patient wearing the proposed AFO, which could be attributed to the flexibility of the SMA wires. However, in their work, the ankle stiffness profiles for different conditions were not plotted, which could be helpful for evaluation of the AFO stiffness. Also, the increase of applied moments on the patients compared to the healthy subject was not discussed. Possible future research on the SMA wire based AFOs will be: (i) finding a way to cover the wire and pulley systems; and (ii) tuning the ankle angle, ankle moment, and ankle stiffness simultaneously instead of focusing just on one outcome. Then, Mataee et al.  only impCorrecting deformities and abnormal postures of the body is another attractive field for utilizing SMA as an orthosis. In this application, much force must be applied to the bones or skeleton for a long time to slowly correct the abnormal shape. The property of SMA in preparing an almost constant force in a large range of deformation, exert and keep a large force on the abnormal part for a long period of time. This may result in a better treatment process with less pain and effort for the user. One of the disadvantages of SMA actuators is the low response time. In rehabilitation applications, there is no need for the users to move the disabled part fast, therefore the relatively slow movement of the rehabilitation device is acceptable. Further, the attractive properties of the SMA actuators as silent work, back drivability, and variable stiffness may result in developing the rehabilitation devices with more functionality in the future. The purpose of this paper is to review biomedical applications of NiTi SMAs in assistive and rehabilitation devices. Assistive devices are categorized to the prosthetic and orthotic devices including elbow, knee, ankle devices, and abnormal deformities correction. This review presented the NiTi assistive devices having a lightweight, silent operation, and high force and being able to mimic the motion of the proposed joint better than conventional devices. Results of this review indicated that there is a need to design assistive devices which can act as a good shock absorber and also tolerate large deformation. Regarding SMAs rehabilitation devices, it’s shown that future research should pay attention to developing more novel and practical rehabilitation devices by employing the unique properties of SMAs.


World Trade Center (WTC) responders were exposed to mixture of dust, smoke, chemicals and carcinogens. Studies of cancer incidence in this population have reported elevated risks of cancer compared to the general population. There is a need to supplement current epidemiologic cancer follow-up with a cancer tissue bank in order to better elucidate a possible connection between each cancer and past WTC exposure. This work describes the implementation of a tissue bank system for the WTC newly diagnosed cancers, focused on advancing the understanding of the biology of these tumors. This will ultimately impact the modalities of treatment, and the probability of success and survival of these patients.WTC Responders who participated (as employees or volunteers) in the rescue, recovery and cleanup efforts at the WTC sites have been enrolled at Mount Sinai in the World Trade Center Health Program. Responders with cancer identified and validated through linkages with New York, New Jersey, Pennsylvania, and Connecticut cancer registries were eligible to participate in this biobank. Potential participants were contacted through letters, phone calls, and emails to explain the research study, consent process, and to obtain the location where their cancer procedure was performed. Pathology departments were contacted to identify and request tissue samples.All the 866 solid cancer cases confirmed by the Data Center at Mount Sinai have been contacted and consent was requested for retrieval and storage of the tissue samples from their cancer. Hospitals and doctors’ offices were then contacted to locate and identify the correct tissue block for each patient. The majority of these cases consist of archival paraffin blocks from surgical patients treated from 2002 to 2015. At the time of manuscript writing, this resulted in 280 cancer samples stored in the biobank.A biobank of cancer tissue from WTC responders has been compiled with 280 specimens in storage to date. This tissue bank represents an important resource for the scientific community allowing for high impact studies on environmental exposures and cancer etiology, cancer outcome, and gene-environment interaction in the unique population of WTC responders. Responders to the World Trade Center (WTC) disaster were exposed to soot, benzene and other volatile organic compounds from jet fuels, as well as WTC dust and smoke, which contained asbestos, silica, cement dust, glass fibers, heavy metals, polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and polychlorinated dibenzofurans and dioxins from the burning and collapse of the planes and the towers –3. ImmedFew studies have investigated cancer incidence in WTC responders. A 2009 study of multiple myeloma cases in WTC responders reported a higher than expected number of cases in responders aged < 45 years old , and repA follow-up study of 20,984 WTC responders linked their data to the tumor registries of New York, New Jersey, Connecticut, and Pennsylvania and identified 575 cancer cases diagnosed from 9/12/2001 to 12/31/2008, 302 of which were diagnosed 6 or more months after the attack . StandarAn updated study of cancer incidence through 2011 among WTC Health Registry enrollees reported increased all-cancer incidence in both rescue and recovery workers (RRW)  and non-rescue and recovery workers  . When coTaken together, the results of these studies have prompted the CDC to add several cancers to the list of WTC-related health conditions  and addeDue to the reported increased cancer incidence, there is a clear need to supplement current epidemiologic cancer follow-up with a cancer tissue bank in order to better elucidate a possible connection between each cancer and past WTC exposure. Biospecimen resources and their clinical annotations are among some of the most powerful resources fueling translational research. This work describes the implementation of a tissue bank system for the WTC newly diagnosed cancers, focused on advancing the understanding of the biology of these tumors. This will ultimately impact the modalities of treatment, and the probability of success and survival of these patients.WTC responders who participated (as employees or volunteers) in the rescue, recovery and cleanup efforts at the WTC sites have been enrolled at Mount Sinai in the World Trade Center Health Program (WTCHP), which is funded under the James Zadroga 9/11 Health and Compensation Act of 2010, on the basis of eligibility criteria including type of duties, site location and dates and hours worked . The fuln = 20,984) were provided to each cancer registry [The WTC Data Center identifies cancer cases through periodic linkages with the cancer registries of New York, New Jersey, Pennsylvania and Connecticut, which accounts for 98% of the responder residences at time of enrollment in the WTCHP . To compregistry . The fulregistry , but onlInitial letters were sent to potential participants explaining the study and seeking approval to discuss the consent process, with information provided for participants to contact the research team with questions Fig. . After tFor cases that were not performed at Mount Sinai, relationships were established with the pathology department at the facility where the procedure occurred. Prior to requesting the sample, the pathology department was contacted to identify and confirm the existence of the correct tissue sample of interest. Afterwards, an official sample request was provided to the hospital/doctor’s office together with a shipping label and a request for the patient’s pathology report. The request included instructions about confirming the diagnosis and identifying the appropriate area of malignancy for sampling. If weeks passed without receiving a sample, hospitals and doctors’ offices were re-contacted to sort out any obstacles.Creating a biobank is a challenge as it is not the policy of many institutions to release their formalin-fixed paraffin-embedded (FFPE) blocks for risk of contamination or the loss of the block. Instead FFPE blocks are sectioned into thin slices using a microtome and placed on glass slides. These slides are sent when samples are requested , 30. AltMaterial received from the various institutions was de-identified and a random number was assigned to each tissue block or set of slides received. If necessary, tissue blocks were processed into tissue slides for storage and then returned at the request of the providing hospital or doctor’s office.Slides were stored in enclosed slide cases in a secure, dry and cool place away from dust and any direct light. It is worth noting that tissue microarrays (TMA) were considered for storage in place of slides but were ultimately decided against. Like tissue slides, TMAs can be constructed from FFPE material and are produced when multiple small tissue “cores” are extracted from different tissue blocks and inserted into one single TMA chip . This cuAll the 866 solid cancer cases confirmed by the Data Center at Mount Sinai have been contacted and consent was requested for retrieval and storage of the tissue samples from their cancer Fig. . HospitaThis biobank serves as a resource available to scientists for etiologic and outcome studies, thus overcoming the historical limitations of other research tissue banks. Access to de-identified clinical data is often complex due to multiple factors including: difficulty of obtaining appropriate control tissues, misconceptions of regulatory and proprietary rules governing tissue banking; specifically IRB, consent, honest broker, de-identification and ownership issues, scarcity of tissues due to lack of cooperation from surgery, pathology, oncology and clinical/translational/basic science researchers who may compete for the same resources.One of the most important aspects of this project is the availability of the tissue samples to the scientific community, with the purpose of allowing high impact studies on environmental exposures and cancer etiology, cancer outcome, and gene-environment interaction in the unique population of WTC responders. We have established a process for qualified applicants to request available samples for use in research projects, and a mechanism for tissue utilization by creating two structures, the research evaluation panel (REP) and the Coordinating Committee (CC).The REP consists of the Principle Investigator of the tissue bank and three other members of the cancer research community and is responsible for determining the importance of the proposed studies, the areas of weakness that require improvement, and for developing recommendations to the CC. The REP review is scientifically rigorous, and a brief written review is requested for internal documentation and to guide discussions with the investigators. The REP convenes regularly by telephone to discuss and approve projects.The Utilization Committee (UC) negotiates the balance between the scientific merit of a proposal as assessed by the REP and sample availability and sustainability for future studies. The UC meets in coordination with the REP and communicates heavily with REP members in order to discuss disagreements and differences in the priorities for sample allocation.The biobank has a governing CC that includes a member from the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) funding agency, the latter of which acts as a resource for information about CDC activities and advises on the acceptability of the CC’s policies to the CDC. The CDC member also has the unique capability of informing other scientists about the availability of the tissue bank. The CC oversees and guides the tissue bank development and ongoing activities, acts as the governing body of the developing operating policies, and has prepared a Manual of Operations for establishing uniform procedures to accession, process, and distribute the tissue samples. The CC determines priorities for application's final approval based on the recommendation of the REP; it also publicizes the availability of this resource to prospective users.After final approval is granted, the research institution requiring the samples must provide IRB approval for the project, and a data-use-agreement between the institution and the biobank must be created. This ensures that tissue samples are only being used for their specific, and approved, purpose. Proposals will only receive de-identified tissue and data, ensuring there is no means to link tissue samples to participants. If two quality research proposals are received for similar projects, we will look for commonality to form collaborations between the two projects, especially if the type and amount of cancer tissue required is limited. Possible limitations of the process include the lack of availability of sufficient amount or type of tissue for the proposed research question, and the possible insufficient number of cases for a certain cancer type.Outreach and advertising of the tissue bank is accomplished through partnership with the WTCHP, CDC, the scientific community and the relevant stakeholders and patient advocacy communities. This approach recognizes that the creation of an effective, sustainable resource is dependent on the participation, trust, and involvement of all these key groups. The existence of the tissue bank, as well as any results generated by using the tissue samples is communicated to WTC members, as well as participants in other WTC surveillance programs.http://icahn.mssm.edu/research/epidemiology/capabilities/biorepository-wtc) that acts as an information portal modeled on previously developed websites by our group. The website includes general information about the type of specimens available, procedures and requirements for obtaining tissue, as well as the electronic forms necessary for making tissue requests and inquiries. The website also includes a password-protected file transfer site, where letters of intent, documentation, publications and other reports  are posted for review by the REP, UC, and CC.The tissue bank is also presented to the wider scientific community through posters at scientific meetings and articles for publication in the medical literature. De-identified raw data generated within this project are made rapidly available to other WTC researchers and the wider medical and preventive community. In an effort to reach out to the community, we have established a secure cloud-based website within the Mount Sinai server  printed brochure to the World Trade Center Biobank. The brochure is currently distributed to major scientific meetings focusing on cancer and epidemiology, and has served as a way to inform the scientific community about the tissue bank.Specialized software is used to provide access-log analysis for the website. This software analyzes the log files created by the web server and provides invaluable information on how users access the website, including statistical information as well as color graphs that show trends and usage. The software periodically analyzes the data and generates reports on samples requests, usage, scientific publications deriving from the tissue bank, number of grants submitted and funded, among others.Initially, there was difficulty in contacting participants by phone because of disconnected numbers, incorrect numbers, and participants not answering their phones or responding to any messages. In some instances, participants had moved or updated their address since their enrollment in the cohort, which prevented the delivery of consent forms. This resulted in a limited number of consent forms returned. However participants were repeatedly contacted multiple times over multiple days at different portions of the day. Home, mobile, and work numbers were used to establish contact together with sending emails to those members of the cohort who had provided their email address. Participants were also contacted by phone in conjunction when consent forms would arrive at their address. This ensured that cases were reminded of the incoming documents and could ask any questions before the forms arrived. Potential participants were also contacted to notify them of an incoming study being mailed to their address.For procedures not performed at Mount Sinai, participants had to be contacted to receive the information at which hospital/office they had their cancer procedure performed. This provided another hurdle in acquiring samples, but an emphasis was made on assessing hospital information whenever contact was made with participants. Requesting samples from outside institutions required locating and establishing contacts with the appropriate member of the pathology department. This entailed completing different procedures for different institutions, which took time to grow accustomed to. In instances where institutions provided tumor blocks instead of slides, blocks were processed at Mount Sinai and returned to the institution as soon as possible.The biobank is in the process of updating the current samples with the cancers that were diagnosed after 2014. To increase participation, employees that speak languages other than English will be recruited for the project. In the future we will continue to address patient’s concerns and fears of participating in the biobank to increase recruitment. We are also working on linking the tissue bank with the main WTCHP data set containing clinical, epidemiological and exposure information, both at the time of inclusion in the WTCHP and during the regularly performed follow up, and to the blood sample collected at baseline.The biobank has also started to standardize and manage a central repository of tissue samples from various organs from rodents exposed to WTC dust; including 376 rats exposed to WTC dusts via intratracheal inhalation –36 by NYFollowing current practice, the biobank of new human and animal tissue will be used as a resource for the scientific community Fig. . The humOf the 280 cancer cases stored in the biobank, 21 are head/neck cancer cases of the larynx, lip, nasopharynx, other oral cavity and pharynx, parotid gland, salivary gland, tongue, and tonsil.These samples have been implemented in a pilot project to test biomarkers for DNA methylation and HPV-genotyping from WTC exposed and unexposed cases. This collaboration is between Rutgers, the State University of New Jersey, Moffitt Cancer Center, and the World Trade Center Biobank at Mount Sinai.WTC first responders have a significant increase in risk of developing thyroid cancer. Together with Johns Hopkins, the ITE and the World Trade Center Biobank at Mount Sinai are conducting a research project to investigate if over-diagnosis of malignant thyroid cancer occurred among WTC responders by using IHC to test molecular markers of thyroid malignancy in archived thyroid cancer tissue from WTC- and non-WTC thyroid tissues.An increased risk of prostate cancer was reported in the WTC responders and recovery workers cohort but the association with WTC-related exposures remains unknown. The ITE and the World Trade Center Biobank at Mount Sinai conducted a proof of principle study of the feasibility of inflammatory biomarkers of prostate cancer using DNA and RNA sequencing. The results of this study will be compared with a parallel study investigating tumor promotion by WTC dust in genetic and metastatic prostate cancer models conducted in collaboration with the Department of Oncological Sciences at Mount Sinai.This is the first attempt to organize a bank of tissue from cancer patients diagnosed after the WTC disaster. Efforts thus far have been concentrated on building the WTCHP and other WTC surveillance programs, organizing participant follow-up, and reporting on cancer incidence through linkage with cancer registries. It is only now, more than 15 years after the attack, that cancer is becoming an important potential health consequence. Since the time frame after the exposure is becoming etiologically relevant for cancer, and the aging cohort is entering a time in life when cancer becomes more frequent, pertinent research can be conducted.Research has estimated an increased cancer burden among WTC-exposed FDNY RRW compared to a demographically similar NYC cohort in the period January 1st 2012 to December 31st, 2013 . This anEtiologic studies demand the availability of properly prepared and stored tissues, making the tissue biobank of WTC samples a necessity for past and incident cancer cases in the future. By law, hospitals and doctors’ offices are only required to keep histopathology slides for 10 years, after which they can be disposed of . EstabliThis repository has valuable immediate and future use through ad hoc designed studies. The linkage with exposure data will allow studying the possible association between WTC exposure and cancer initiation and progression. The inclusion of clinical data allows for studying genetic markers in relation to cancer characteristics and aggressiveness, thus addressing the possibility that cancer in WTC responders differs from cancer in an unexposed similar population.In order to study the effect of WTC-related exposures on clinical cancer characteristics it is necessary to conduct genomic research studies, studies of gene-environment interaction, as well as DNA methylation studies , 39. TheFinally, future studies on the biological material banked would be able to observe if cancers developed later on during the follow-up differ biologically from cancers developed in the immediate aftermath of the WTC disaster, thus helping to disentangle the role of the WTC disaster on cancer occurrence.A biobank of cancer tissue from WTC responders has been compiled with 280 specimens in storage. This tissue bank represents an important resource for the scientific community allowing for high impact studies on environmental exposures and cancer etiology, cancer outcome, and gene-environment interaction in the unique population of WTC responders.


Sleep is essential for human health and functioning. Parents of preterm infants are susceptible to sleep disturbances because of stress related to the preterm birth. Poor sleep has the potential to affect parental health and well-being. The aim of this study was to identify and map evidence on sleep and its relationship to health in parents of preterm infants. No review has summarized the evidence on this topic.A scoping review was conducted. Seven health and medical electronic research databases were searched for relevant quantitative and qualitative primary studies, including grey literature. The search was performed March 2–7, 2017.Ten American studies and one Australian study were included in the review. Most research was quantitative and focused on maternal sleep and mental health within the first two weeks after the childbirth. Both objective and subjective sleep measures were used to study sleep at the hospital; actigraphs were not used after discharge. Maternal sleep was poor early postpartum, and this was associated with negative health outcomes. Two cohort studies compared sleep in mothers of preterm and term infants, but the results were conflicting. In one qualitative study, fathers described their inability to catch up on sleep after homecoming with a preterm baby.Quantitative studies reporting on maternal sleep early postpartum was most frequently occurring in the results. Qualitative research on the topic was identified as a knowledge gap. More cultural and geographical breadth, including research on fathers’ sleep, is recommended in future research. Every year, approximately 15 million infants around the world are born before 37 completed weeks of gestation, and the rate of preterm birth is increasing . DependiSleep is a multidimensional, biobehavioural process that is essential for human health and functioning . AlthougDuring the postpartum period, sleep disturbances are common among new parents . The posIn healthy postpartum women, poor sleep has been associated with stress and adverse wellbeing , fatigueWhat study designs have been used to investigate relationships between sleep and health in parents of preterm infants?Which research instruments have been used to study relationships between sleep and health in parents of preterm infants?What outcomes have been reported regarding sleep and its relation to health in parents of preterm infants?The objective of this scoping review was to identify and map information on sleep and its potential relationships to parental health among parents of preterm infants. More specifically, the review focused on the following questions:This scoping review was based on the methodology and guidance for conducting systematic scoping reviews developed by Arksey and O’Malley  and furtThe search strategy aimed to trace both published and unpublished studies up to March 7, 2017. To prepare for the search process, an identification of the main concepts inherent in the research questions was guided by the elements of a PICOC structure  . Three mAfter the searches in seven electronic databases, the identified papers were transferred to Endnote Reference Manager for removal of duplicates and further exported into a Microsoft Excel format for screening of titles and abstracts. Only studies meeting the inclusion and exclusion criteria were eligible for inclusion in the review. The inclusion criteria were the following: primary studies of quantitative or qualitative design published in English, reporting on sleep in parents (mothers or fathers) of preterm infants , and parents’ health issues up to one year after the birth of the preterm infant. Health aspects were understood according to the World health organization (WHO’s) definition of health  and cateBased on the current methodological guidelines for scoping studies , 41, no A data extraction sheet was developed to determine which variables to extract to answer the research questions. Each study was screened and extracted according to author, year of publication, country of origin, study design, purpose of study, population, and research instruments used to study sleep and health. A summary of the key findings was also extracted from each study. The results are presented in tables Tables  and 2. DConsistent with the methodology used in this review, the collating, summarizing and reporting of results were guided by Levac et al.’s recommendations . The metAfter completing the screening process, eleven studies were ultimately included in the review. Nine studies were retrieved as articles –54, and Ten of the included studies used a quantitative design, and only one used a qualitative design Table . Among tIn the quantitative studies, a variety of research instruments were used to study sleep. Six papers reported on objective sleep data derived from wrist actigraphs, which are small monitors used to assess rest-activity patterns . The actDifferent research tools have been used to study health, with PROMs being used most commonly in the literature. Only one study reported on objective measures exclusively . Twelve In the early phase after childbirth, maternal sleep was described as poor. Data derived from actigraphs indicated that maternal total sleep time (TST) was less than 7 h –51. SleeAccording to the outcomes of their sleep, some mothers were more susceptible than others to experiencing poor sleep. Shelton et al.  comparedTwo clinical trials were identified in the material. Both interventions were developed to promote maternal sleep and health early postpartum. Lee et al.  tested tAs shown above, different health outcomes were reported in the included studies Table . Only fiIn neonatal care, care provision is influenced by parental mental health and well-being . The abiTo the best of the authors’ knowledge, this was the first scoping review to summarize the existing evidence on sleep and its relationships to health in parents of preterm infants. The strengths of this review are its broad and comprehensive search in the electronic databases, inclusion of quantitative and qualitative literature, and lack of restrictions on date range in the literature searches. One limitation of the findings in this scoping review is the lack of cultural and geographical breadth. The included research was predominated by studies from U.S, resulting in findings with geographical concentration in western societies, and study populations characterized by ethnic specificity , 50, 51.Another limitation was the lack of qualitative research in this review’s findings. Qualitative research is considered to be especially useful in contributing with in debt knowledge and a deeper understanding of complex human phenomenon’s , and couThis review addresses concerns about parental sleep, health and well-being. Despite limitations on the applicability of the results to parents globally, efforts to promote sleep and health may be a prominent issue for health care providers in hospital settings worldwide. More needs to be learned about fathers’ sleep and health and about whether the long-term consequences to sleep and health differ for parents of preterm infants. Knowledge of sleep and health characteristics might be the first step toward developing efforts and interventions to promote a healthy parent population.


To support healthcare professionals in dealing with ethically difficult situations, Clinical Ethics Support (CES) services like Moral Case Deliberation (MCD) are increasingly implemented. To assess the impact of CES, it is important to evaluate outcomes. Despite general claims about outcomes from MCD experts and some qualitative research, there exists no conceptual analysis of outcomes yet. Therefore, the aim of this study was to systematically define and categorize MCD outcomes. An additional aim was to compare these outcomes with the outcomes in the Euro-MCD Instrument from 2014, to further validate this Instrument.The concept mapping method was used and involves qualitative and quantitative steps including brainstorming, individual structuring, computation of concept maps , group interpretation and utilization. In total, 12 experienced MCD participants from a variety of professional backgrounds participated in two sessions.The focus group brainstorm resulted in a list of 85 possible MCD outcomes, of which a point map and concept maps were constructed. After a thorough discussion of each cluster, final consensus was reached on the names and position of 8 clusters of MCD outcomes: 1) Organisation and Policy; 2) Team development; 3) Personal development focused on the Other Person; 4) Personal development as Professional, focused on Skills; 5) Personal development as Professional, focused on Knowledge; 6) Personal development as an Individual; 7) Perception and Connection; and 8) Concrete action.This study explored and categorized MCD outcomes in a concept mapping focus group. When comparing the results with the Euro-MCD Instrument, our study confirms that outcomes of MCD can be categorized in clusters referring to the organisational level, team development, personal development  and the concrete case-level. In developing CES evaluation tools, it is important to be explicit if an outcome refers to the individual or the team, to knowledge or skills, to the organisation or the specific case. The findings will be used in the further validation of the Euro-MCD Instrument. The current study further contributes to the field of evaluating CES in general and defining outcomes of MCD in particular.The online version of this article (10.1186/s12910-018-0324-z) contains supplementary material, which is available to authorized users. Healthcare professionals are confronted with ethically difficult situations every day. When aiming for good care, they face moral questions like: What is good care in this situation? Who should determine what good care is? How to deal with different viewpoints on good care? Clinical Ethics Support (CES) aims to help healthcare professionals in dealing with these situations. CES can take many forms, one of which is Moral Case Deliberationsupports healthcare professionals in dealing with ethical challenges, and if so, in which way. Furthermore, evaluation results can be used for the training of future MCD facilitators [should be (e.g. which outcomes are appropriate and which are not?).While the presence of and need for CES services like MCD is increasing , empiriclitators  and the litators . FinallyRecent evaluation research in the field of MCD showed positive results regarding the participant’s need for and their satisfaction with the CES services , 8–14. Hnormative goals of MCD. Yet, experiences from MCD participants play an important role in defining possible outcomes since they are the actual users of MCD. They can, based on their experiences with MCD, help in reporting which outcomes they experienced and how they think MCD outcomes are connected to one another.Since MCD aims to support healthcare professionals and because MCD focuses on the experiences and perspectives of the MCD participants themselves, it is important to involve actual MCD participants in empirical research about possible MCD outcomes. This does not imply that outcomes that are reported, experienced or valued by MCD participants should automatically become the In order to contribute to the professionalization of both MCD itself as well as the evaluation research of MCD, a European research project on outcomes of MCD has been started. In this project, an MCD evaluation tool called the ‘Euro-MCD Instrument’ has been developed . The EurAlthough the Euro-MCD Instrument asks for the input of MCD participants regarding their perceived importance and experience of MCD outcomes, MCD participants did not play a role in the development of the instrument. Therefore, it is yet unknown what outcomes they would mention themselves and how they would categorize these outcomes. In order to explore and define possible MCD outcomes as mentioned by experienced MCD participants and to form an evidence-based categorization of these outcomes, the current study was performed. The ultimate goal of the larger Euro-MCD field study (of which this study was part of) was to improve and further validate the current Euro-MCD Instrument in order to professionalize future CES and MCD evaluation research. Therefore, we compared the findings with the original items of the Euro-MCD Instrument in the Discussion section.Concept mapping is a methodology for conceptualization and categorization of a complex topic , 19. A ‘We will now describe how we performed these six steps.focus statement [In the preparation phase, the research team determined the focus for the concept mapping by articulating the tatement : ‘What aThe first step further consisted of selecting the participants. The aim in our study was to form a group with experienced MCD participants, preferably from many various settings where MCD is practiced and from diverse professional backgrounds. They were recruited by JDST in two ways: 1) by inviting all trainees of the current Dutch national training program for becoming a MCD facilitator, and 2) by inviting members of the national network of certified and experienced MCD facilitators. Trainees needed to have extensive experience with participating in MCD sessions before the start of the training program [The second step formed the start of the actual concept mapping process. The aim was to generate a list of statements that ‘ideally, will represent the entire conceptual domain for the topic of interest’ .During the first meeting, the facilitator (ACM) firstly asked focus group members to take 10–15 min to think of possible MCD outcomes individually. He then asked them to present their statements one by one. The statements were directly entered into a word processing program by a research team member (JDST) and projected on a large screen. By this, all focus group members could see the statements and discuss the distinctiveness and clarity of them, as it was important that everyone understood and agreed on the generation of statements .After the round in which participants shared their own statements, one member of our research team (JDST) presented additional MCD outcomes from the Euro-MCD study that were not yet included in the list made during the focus group. These outcomes came from the list of 26 items of the Euro-MCD Instrument and outcomes mentioned by Dutch respondents to the open question in the instrument asking for possible MCD outcomes . The chaThe step of sharing and refining would finally result in a list of unique and clear statements. The facilitator (ACM) aimed to generate no more than 100 statements, in order to avoid practical difficulties with the next steps of the concept mapping process .In the third phase, focus group members were asked by the facilitator (ACM) as an individual task to structure the statements into piles “in a way that makes sense to you”  and to gIn our study, the research team printed all outcomes from the brainstorm on separate cards, and gave everyone the complete set of cards. After the individual sorting task, we collected all piles including names with paper clips and put them into envelopes; one envelope per focus group member.The fourth phase consisted of the computation of concept maps based on the thematic clusters (piles) made by all focus group members individually. This was done in-between the two sessions, in which the research team (JDST and HCWDV) entered the piles from all members into a concept mapping software program, Ariadne . This soA month after the first session, the second session was organized. In the fifth step, the concept map was discussed and interpreted with the focus group. Firstly, the point map and concept map were presented to the focus group. Secondly, focus group members were asked by the facilitator (ACM) to take some time to read all statements and explore their place on the map, and to write down possible names for each cluster. Thirdly, the focus group engaged in a dialogue about the map. Cluster by cluster, members presented their thoughts and names and tried to reach agreement on the final name of each cluster. This phase could also include refining clusters by changing the position of separate statements.In our study, the research team showed the concept map on the screen and on paper for each focus group member. The facilitator (ACM) aimed to reach consensus among the participants on the final number and naming of clusters, by discussing them cluster by cluster. If no consensus could be achieved, the majority decided, but other research team members (JDST and HCWDV) made a note of this. The facilitator of the focus group (ACM) invited members repeatedly to express their opinions, in particular if they disagreed with others regarding the number and naming of the clusters. Those who still disagreed after discussion could withdraw from further discussion on the naming or content of that specific cluster. All disagreements and withdrawals from discussions on clusters were reported by the research team.The final concept map can be used for planning and evaluation purposes. With regard to evaluation, it can be seen as a guide for measurement development, or as a framework for examining patterns of outcomes as it provides a clear overview of statements and their mutual relations . For insThe research team compared the final statements and clusters of the concept map with the original outcomes and domains of the Euro-MCD Instrument. This will be described in the Discussion section.Conform the ethical principles for medical research as stated in the Declaration of Helsinki , all focIn total, 12 experienced MCD participants, from a variety of professional backgrounds, took part in the concept mapping focus group. The characteristics of them are presented in Table In the first session, the brainstorm phase resulted in a list of 85 unique and clear statements, according to the focus group members, as presented in Additional file All focus group members finished the step of individual structuring. They sorted the statements into 5–20 piles. Figure The cluster analysis provided the possibility to construct 2 to 12 clusters, which were discussed with the research team . The concept map of 10 clusters was chosen as starting point for the next session of the focus group see Fig.  because The concept map with 10 clusters was discussed with the focus group in the second session, with the aim to find consensus on the number and naming of the clusters, as described in the Methods section. Focus group members were explicitly asked to express their (dis)agreement with categorizations and possible names of clusters. This was the case during the categorization or specification of a few clusters, which will be described to more detail below. In the end, after some statement replacements, consensus was achieved on the names and position of all statements in 8 final clusters. The final concept map is presented in Fig. The first discussed cluster was cluster A in Fig. The focus group members quickly reached consensus on the name of the second cluster  and F (5) in Fig. The statements in cluster 6 . Due to this, they brought a large variety of statements into the brainstorm phase and at the same time were able to critically analyze the final list of statements. During the step in which they had to make piles of the statements, the number of piles differed. One focus group member distinguished only 2 thematic clusters covering all 85 outcomes while other distinguished up to 20 thematic clusters. A step for step dialogue in which they had the possibility to explain how they thought about the differentiation of clusters, relatively easily led to an agreement about how many clusters there should be. Furthermore, a surprising finding was that with regard to some clusters , consensus was easily reached, possibly indicating that the cluster was recognizable as a specific theme and probably clearly enough constructed. However, the discussion about the other clusters took a while, and some focus group members did not contribute to the formulation of cluster names as they did not support the positioning of some clusters. Nevertheless, in the end, all focus group members agreed on the final naming and categorizing of the 8 clusters, despite the minor disagreements during the cluster discussions.When exploratively reviewing literature, we found some  of these clusters as well. For instance, in the focus group study of Hem et al. , particiAccording to the second aim of this paper and the sixth step of concept mapping  and in lWhen comparing the final cluster names with the names of the Euro-MCD domains, several links can be made: Concrete Action with Concrete Results; Organisation and Policy with Impact on Organisational Level; Team development with Collaboration. Furthermore, when looking at the Euro-MCD domain Emotional Support, we see a link with our cluster Perception and Connection, as both include feelings and emotions like ‘self-confidence’, ‘managing stress’ and ‘feeling secure’. Finally, the Euro-MCD domains Moral Reflexivity and Moral Attitude can be compared with the clusters about personal development (clusters 3–6), as they all include outcomes referring to self-reflection, like ‘I gain more clarity about my own responsibility in the ethically difficult situations’ and ‘Increases my awareness of the complexity of the situation’. Fortunately, we can therefore conclude that the original categorization of MCD outcomes by MCD experts in the Euro-MCD Instrument can be confirmed to some extent, despite the fact that their categorization was not yet based on empirical data at that time .However, several differences can be found as well when comparing the Euro-MCD domains with the clusters of the concept map. Firstly, the Euro-MCD domains Emotional Support and Collaboration seem to be reflected in more than 2 focus group-clusters, namely Team development, Personal development focused on the Other Person and Perception and Connection. Secondly, the Euro-MCD domains Moral Reflexivity and Moral Attitude cannot be recognized easily in the focus group-clusters, since terms like ‘reflexivity’ or ‘attitude’ were not used. These domains are about analytic skills, awareness and understanding of ethically difficult situations. Yet, the focus group members made a distinction between skills and knowledge in their separate clusters about personal development as a professional (4 and 5). To conclude, we can say that the focus group members defined additional and more detailed categories of outcomes that match with outcomes from the Euro-MCD domains Moral Reflexivity and Moral Attitude, namely based on whether the outcome was about personal or professional development, about oneself or directed to the other, and about skills or about knowledge. This resulted in 4 separate clusters (3–6) for personal and professional development, and skills and knowledge. This difference in nuances might be explained by the fact that the definition of the Euro-MCD domains of Moral Reflexivity and Moral Attitude was based on theory, literature and the opinion of MCD experts , while toutcomes and not the process of MCDs themselves. Future qualitative studies should investigate what kind of negative outcomes MCD participants report, whether they refer to literally negative or harmful outcomes or a lack of expected positive outcomes, and in which way they are related to MCD as such. This is important in order to avoid a bias in presenting (only positive) MCD evaluation results. Furthermore, negative MCD outcomes could be helpful in improving, adjusting or not using MCD as ethics support mechanism. Furthermore, we should reflect upon the question whether we should pay attention to negative MCD outcomes in the further validation of the Euro-MCD Instrument.An interesting difference between this study and the Euro-MCD Instrument is the formulation and position of possible negative outcomes (‘Disappointment about outcome’ and ‘Sense of wasting time’) in the focus group cluster Perceiving and Connecting, while the Euro-MCD domains only contain positively formulated outcomes. The formulation of these two negative outcomes was a surprising finding in our study, although the number of two might be a quite low number. We think and literature shows that MCD might cause negative outcomes as well, like frustrations about the lack of solutions  or not eOne of the strengths of this study was the fact that the concept mapping procedure consisted of structured and systematic conceptual-analytical steps in which qualitative and quantitative measures were integrated within a reflective open dialogue. A main strength of our study was the composition of the focus group: members came from various professional backgrounds, in diverse settings of MCD, both inside and outside healthcare, and were all very experienced as participants in MCD. As such, they were no specific ‘experts’ in evaluation research, instrument development, but people from a broad range of settings were MCD is practiced. They were all present and actively involved in both sessions of the focus group, and they all had a critical and analytical yet constructive contribution. This might be caused by the fact that they were experienced MCD participants and thus were used to group sessions with equal participation, a critical dialogue, being open towards different perspectives and letting others express their thoughts. The final concept map with named clusters is a product of the participants themselves, as it was based on statements that they generated in their own words, with extra input from the original Euro-MCD. Furthermore, a methodological strength was that we were able to complement the brainstorm among the focus group members with data from the large Euro-MCD field study as well, in order to get as rich data as possible. Lastly, the focus group members achieved a relatively strong agreement on the final names and categorization of the clusters, resulting in an experience- and consensus-based categorization of MCD outcomes.Yet, our study has limitations as well. The study contained only one focus group consisting of two sessions in only one country, due to limited time and financial resources. Since we needed experienced MCD participants, the Netherlands was a good candidate for performing this study as MCD is implemented in this country for a long time . It is ipossible MCD outcomes with use of the qualitative and quantitative method of concept mapping. Based on these descriptive results, in a future empirical-ethics study, one can start to reflect upon the normative question whether possible outcomes are also desirable outcomes, and for which reason. The study provides valuable lessons for further evaluation research on outcomes of CES services and outcomes on MCD in general. Most importantly, the current study confirms that outcomes of MCD can be categorized in clusters referring to the personal development , team development, the organisational level and the concrete case-level. Moreover, according to the focus group members in the current study, several (clusters of) outcomes of MCD are related to the cooperation with colleagues, and even feelings and emotions are involved here (in the cluster Perception and Connection). Furthermore, MCD could have an impact on the way participants would act in practice and on policy making at the organisational level. Therefore, in developing measurement tools, it is important to be explicit if an outcome refers to knowledge, or skills, to the person him/herself or to his or her professional role, or to the team, organisation or the specific case.On the bases of a Dutch focus group study with experienced MCD participants, this paper presented 8 thematic categories for According to the ultimate goal to further validate the Euro-MCD Instrument of 2014 , in the Additional file 1:Characteristics of Dutch Respondents in Euro-MCD study. This file shows the characteristics of Dutch healthcare professionals who participated in the Euro-MCD study. In this study, they completed a questionnaire (the Euro-MCD Instrument). This questionnaire includes an open question regarding possible outcomes of Moral Case Deliberation, defined and perceived as important by the respondent. The answers on this question were used in the current study. (DOCX 14 kb)Additional file 2:List of outcomes of Moral Case Deliberation. In this file, the list of 85 outcomes of Moral Case Deliberation is presented, as identified and defined by the participants during the brainstorm phase of the concept mapping focus group. (DOCX 17 kb)


In 2011, we launched the Smarter Pregnancy mobile health  coaching program, which has shown to effectively improve inadequate nutrition and lifestyle behaviors in women before and during pregnancy. It is known that in deprived neighborhoods, risk factors for adverse pregnancy outcomes like inadequate nutrition and lifestyle behaviors accumulate. However, it has not yet been investigated whether the Smarter Pregnancy program is equally effective in women living in deprived neighborhoods.This paper aimed to study the associations between neighborhood deprivation and improvement of inadequate nutrition and lifestyle behaviors of women who were either contemplating pregnancy or already pregnant and subscribed to the Smarter Pregnancy program.We performed an additional analysis on data from women who used the Smarter Pregnancy program from 2011 to 2016. The program comprised 24 weeks of coaching on 5 nutrition and lifestyle behaviors, of which adequate intakes or lifestyle behaviors were defined as an intake of 200 grams or above of vegetables, 2 pieces of fruit, daily folic acid supplement use of 400 µg per day, and no smoking or alcohol consumption. Neighborhood deprivation was determined according to the status scores of the Netherlands Institute for Social Research. Logistic regression analyses and generalized estimating equation models were used to assess the associations between the neighborhood status score (NSS) and the improvement of inadequate nutrition and lifestyle behaviors, taking into account the behaviors at baseline. We adjusted the analyses for maternal age, body mass index, geographic origin, pregnancy status, and participation as a couple.Of the 2554 women included, 521 participated with their male partner. Overall, daily vegetable intake was most frequently inadequate at the start of the program . Women with a higher NSS  smoked less often , consumed alcohol more often , and were less likely to complete the 24 weeks of coaching  compared with women who lived in a neighborhood with a low NSS . In the total group, the relative improvement of inadequate nutrition and lifestyle behaviors after 24 weeks of coaching was between 26% and 64%. NSS was negatively associated with this improvement, indicating that women with a higher NSS were less likely to improve inadequate nutrition and lifestyle behaviors, especially vegetable intake .The Smarter Pregnancy mHealth coaching program empowers women to improve inadequate nutrition and lifestyle behaviors. Unexpectedly, the program seemed more effective in women living in deprived neighborhoods. It is important to unravel differences in needs and behaviors of specific target groups to further tailor the mHealth program on the basis of demographic characteristics like neighborhood deprivation. Worldwide, there are substantial differences in perinatal morbidity and mortality rates between and within countries, which may indicate inequalities in perinatal as well as population health ,2. SeverRisk factors for adverse pregnancy outcomes, such as poor nutrition, lifestyle and housing conditions as well as lower health literacy, often accumulate in residents of deprived neighborhoods ,9,10. HoAccording to the transtheoretical model of behavioral change, intentional behavioral change can be achieved after passing 6 different stages, from precontemplation to maintenance and termination .However, behavioral change is more challenging for individuals who have limited health literacy or impaired financial resources, who are less educated, and live in more deprived neighborhoods ,17,18. FCurrently, mobile health  apps are widely available and used for health improvement. mHealth apps can be designed to a specific population and target of interest and may be offered anytime and anywhere at low costs. Therefore, mHealth is a promising medium to support people to improve nutrition and lifestyle behaviors ,20. In 2Previously, van Dijk et al analyzed survey data of all subscribers to the Smarter Pregnancy program to assess compliance, feasibility, usability, and first effectiveness of the program. It was shown that the program contributes to significant improvements of inadequate nutrition and lifestyle behaviors—that is, vegetable (+26%) and fruit intake (+38%), folic acid supplement use (+56%), smoking (−35%), and alcohol consumption (−42%)—in couples before and during pregnancy, which also resulted in an enhanced pregnancy chance in both fertile and subfertile couples up to 40%. Besides, a high compliance (65%) and usability were reported ,24.However, it has not yet been investigated whether the Smarter Pregnancy program is equally effective in women who live in deprived neighborhoods. Therefore, our current aim was to investigate in an additional analysis, associations between neighborhood deprivation and the improvement of inadequate nutrition and lifestyle behaviors of women before and during pregnancy who previously subscribed to the Smarter Pregnancy program.We used the data of an epidemiological survey conducted among all women who subscribed to the Smarter Pregnancy program for an additional analysis . Women aThe coaching model developed for the Smarter Pregnancy program is based on the most recent knowledge on the effect of vegetable, fruit, and folic acid supplement intake, smoking and alcohol consumption on pregnancy chance, course, and outcome ,25,26. FThe coaching program starts with a baseline screening on nutrition  and lifestyle  behaviors that significantly affect fertility and pregnancy course and outcome . The mHeData were collected through the Smarter Pregnancy program itself. Demographic characteristics and anthropometric measurements of the participants were retrieved from the Smarter Pregnancy database—zip code, sex , age (continuous), pregnancy status (pregnant or not pregnant), and BMI . Geographic origin was not reported by participants themselves. Therefore, we used the surnames of the participants to ascribe them a geographic origin, a method that is considered valid when self-identification is not available . ClassifCompliance to the Smarter Pregnancy program was defined as the percentage of participants who filled in the last questionnaire of the program after 24 weeks of coaching. At baseline and after 24 weeks of coaching, the reported nutrition and lifestyle behaviors were classified as adequate or inadequate. Adequate behavior was defined as a daily intake of at least 200 grams of vegetables and at least 2 pieces of fruit, daily folic acid supplement use of at least 400 µg starting before conception and lasting until the 12th week of pregnancy, and no smoking or alcohol consumption .To adjust for nutrition and lifestyle behaviors, a total risk score (TRS) was calculated. For vegetable and fruit intake, folic acid supplement, and alcohol use, 0 points were assigned in case a participant had an adequate intake or use . For inaTo assign participants a neighborhood deprivation state, the status scores of the Netherlands Institute for Social Research were used. These scores follow a standard normal distribution by design and are calculated for all 4-digit zip codes in the Netherlands on the basis of 4 neighborhood characteristics—the average income, the number of nonemployed residents, the number of lower educated residents, and the number of households with a low income . When thAll participants who started the program were included in the analysis at baseline. However, improvement of nutrition and lifestyle behaviors was only examined in those individuals who scored inadequate at any of these behaviors at the start of the program. To minimize selection bias, multiple imputation using chained equations was performed to handle missing data of women who prematurely resigned from the program. For those women, it was assumed that the adequacy of their nutrition and lifestyle behaviors at the last reported screening moment would not have changed until the end of the program (24 weeks).Univariate linear and logistic regression analysis was used to study associations between demographic characteristics of the study population  and the NSS at the start of the program. Logistic regression analysis was used to examine the association between the NSS and (in) adequate nutrition and lifestyle behaviors at the start of the program. To study the improvement of inadequate nutrition and lifestyle behaviors after 24 weeks of coaching, generalized estimating equations with an independent working correlation matrix were used to model the fraction of the study population that scored inadequate at baseline, taking into account that less improvement may be expected when less women show inadequate behavior at baseline. Interaction tests were performed to study interactions of geographic origin, participation as a couple, or being pregnant at the start of the program on the association between NSS and nutrition and lifestyle behaviors.P<.05 values were considered statistically significant. No alpha adjustment for multiple comparisons was made.Statistical analyses were performed using SPSS version 21 software package (IBM Corp) and R version 3.4 . Details of ethical approval included the following: This survey was conducted according to the guidelines laid down in the Declaration of Helsinki. All procedures involving patients were approved by the Medical Ethical and Institutional Review Board of the Erasmus MC, University Medical Centre, Rotterdam, the Netherlands . Digital informed consent was obtained from all participants.A total of 3776 women registered to the Smarter Pregnancy program, out of which 32.36% (1222/3776) of the women were excluded because of absence of activating the registration, incomplete registration, or incomplete data entry at the start of the program . ConsequWomen with a higher NSS  were older  and more often participated as a couple . Moreover, these women were more often pregnant at the start of the program , had a lower BMI , and were less often of non-Western geographic origin  but more likely to consume alcohol  compared with Western women . This difference between non-Western and Western women was not observed for the association between the NSS and improvement of alcohol consumption.Following the results of van Dijk et al, this study demonstrated that women improve their inadequate nutrition and lifestyle behaviors after 24 weeks of mHealth coaching using the Smarter Pregnancy program . HoweverCurrently, a growing number of mHealth apps are developed for personal lifestyle and medical health care support. These apps provide interaction and targeted information on particular domains for specific target groups, and improvement in self-reported health behaviors because these apps are observed. Specifically, decreased tobacco use, increased vitamin intake, and more frequent healthy food intake have been reported after coaching by apps designed to encourage healthy behavior. Therefore, in our opinion, it is important to conduct profound research both in low- and middle- as well as in high income countries before these apps can be implemented in medical health care .In this study’s population, women who lived in less deprived neighborhoods were less likely to smoke but more likely to consume alcohol, which is in line with previous studies ,35,36. DStrengths of this study are the large number of included participants (N=2554), the high overall compliance of 68.17% 1741/2554) of women who completed the 24 weeks of coaching, the fact that several potential confounders were taken into account in the adjusted models, and the imputation of missing data. In this study, NSS—based on a well-defined index—was used as a proxy for socioeconomic health inequality among neighborhoods. This continuous measure of neighborhood deprivation was used instead of a dichotomous measure , which provides a more precise evaluation of the effect of neighborhood deprivation. The use of area-based indices as a proxy for socioeconomic health is well supported in the literature; thus, the used neighborhood deprivation index can be considered a valid indicator ,41. NSS /2554 of Despite the fact that the inclusion period of the study population and the coaching with the Smarter Pregnancy program covers several years, the NSS of 2014 was used as the measure of neighborhood deprivation for the whole study population. As the NSS and the ratio of score among the neighborhoods do not change much over time, we consider this a valid determinant of the neighborhood deprivation within the study population.Although geographic origin is known to be a potential confounding variable for associations with deprivation, information regarding geographic origin was not directly available from our database. To take geographic origin into account, we retrospectively performed geographic classification. This approach is considered a valid method for ascribing individuals to geographic groups when self-identification is not available , but unfLimitations of this study are the absence of validation of nutritional status by biomarkers and the absence of a control group, although this is inherent to this study’s design. Furthermore, the Smarter Pregnancy program was only available in Dutch and on multiple devices with internet access and preferably a mobile phone. Consequently, only those familiar with the Dutch language and in possession of a mobile phone with internet access participated. Over 95% of all women and men of reproductive age living in the Netherlands have internet access on their mobile phone, making the program properly accessible . HoweverOverall, we can conclude that the Smarter Pregnancy mHealth coaching program is able to motivate and support women from more and less deprived neighborhoods to improve their nutrition and lifestyle behaviors. However, women who live in more deprived neighborhoods seem to improve their nutrition and lifestyle behaviors more compared with women from less deprived neighborhoods.Together, these findings underline the need for a more tailored version of the program, adapted to the needs of its participants on the basis of demographic characteristics, so that the program can adequately and optimally empower all women to improve their nutrition and lifestyle behaviors.