Hip dysplasia is a developmental disorder that results in anatomic abnormalities in which the acetabular coverage is insufficient. In the absence of severe degenerative changes, younger active patients with these symptomatic structural abnormalities are increasingly managed with joint-preserving operations. Historically there have been numerous reconstructive pelvic osteotomies. In recent years, the Bernese periacetabular osteotomy (PAO) has become the preferred osteotomy by many surgeons. Even so, as our understanding of the hip advances and new diagnostic and treatment techniques are developed, we sought to put a focus on the long-term results of augmental osteotomies and pelvic osteotomies other than the PAO, to see if any of these surgeries still have a place in the current algorithm of treatment for the dysplastic hip. As the longevity of the treatment is the focal point for joint preservation surgeries for the dysplastic hip, these authors have searched databases for articles in the English literature that reported results of long-term follow-up with a minimum of 11-year survivorship after surgical treatment of developmental dysplasia of the hip. Reconstruction osteotomies for the dysplastic hip are intended to restore normal hip anatomy and biomechanics, improve symptoms and prevent degenerative changes, in this manuscript each procedure is independently assessed on the ability to achieve these important characteristics. Hip dysplasia is a developmental disorder that results in anatomic abnormalities in which the acetabular coverage is insufficient, predisposing the hip joint to have increased contact pressure on the cartilage as well as instability which leads to damage to the soft tissue structures surrounding the joint, eventually leading to coxarthrosis. In the absence of severe degenerative changes, younger active patients with these symptomatic structural abnormalities are increasingly managed with joint-preserving operations with the goal of improving function and possibly preventing the development of severe degenerative changes. For this purpose, many variations of augmental osteoplasties and pelvic osteotomy surgeries have been proposed.Historically in adolescents with a closed triradiate cartilage and in young adults, there have been numerous reconstructive pelvic osteotomies, with each surgery aiming to address the problems of the earlier generation procedures, in an attempt to improve on the results . In receReconstruction osteotomies for the dysplastic hip are intended to restore normal hip anatomy and biomechanics, improve symptoms and prevent degenerative changes. Theoretically, the ideal osteotomy should be as non-invasive as possible, technically reproducible, have sufficient graft mobility, have the ability to increase the area of weight bearing hyaline cartilage, medialize the center of rotation, have reliable blood supply for the graft, be a stable osteotomy, and have a broad range of indications. In this manuscript, each procedure is independently assessed on the ability to achieve these important characteristics.Salter introduced the single innominate osteotomy in 1961 . Salter Because of its simplicity and its wide spread use in the 1970’s, the Salter innominate osteotomy was also utilized in adult patients. But because the osteotomy relies on the symphysis pubis as a pivot, the obtainable degree of correction in an adult patient was limited. The center of rotation of the hip is also moved laterally, which increases the stresses over the hip joint causing concern in the adult patient. The surgery has since lost its place in the treatment of the skeletally mature patient.et al. [et al. [The long-term results of the Salter single innominate osteotomy have exclusively been reported in the young child, with many series reporting excellent results. Böhm et al.  and Thom [et al.  have pre [et al. .Table IMany of the ideal theoretical goals are achieved. It is a fairly non-invasive and reproducible surgery. There is increase of the weight bearing area of Hyaline cartilage. The movability of the graft is constrained and medialization cannot be obtained. The osteotomy is stable and the blood supply to the graft is good, and there is limited narrowing of the pelvic ring. The level of dysplasia that can be treated with this technique is limited, however, and can only be use effectively in young children .The Acetabuloplasty operations are operations exclusively done in children for the treatment of DDH. These operations should be noted for their historic importance in the evolution of pelvic osteotomy, but because they are surgical techniques that cannot be done in the skeletally mature patient, they are not considered as an alternative to the PAO. As such, these operations will only briefly be reviewed. Acetabuloplasty procedures are operations designed to change the slope of the roof of the acetabulum by making an incomplete osteotomy above the joint and hinging down the graft with the acetabular roof and insertion of a bone graft to keep the osteotomy site open , 8. PembThe double innominate osteotomy was introduced by Sutherland and Greenfield . This suCompared with the Salter osteotomy it is a more invasive surgery. There is increase of the weight bearing area of Hyaline cartilage. The movability of the graft is still constrained and optimal medialization can be difficult. The osteotomy is stable the blood supply to the graft is stable, and the narrowing of the pelvic ring is limited. The level of dysplasia that can be treated with this technique is limited .Triple innominate osteotomies were described to overcome the drawbacks of the Salter innominate osteotomy, especially addressing the restricted movement of the fragment and the lateralization of the hip joint. The basis of this operation was to make an osteotomy of the pubis and ischium, to allow for more freedom to move the fragment. The operations described by LeCoeur , Hopf 1 and SteeLeCoeur was the first to publish a technique for triple osteotomy of the innominate bone. The method divides the pubis and the ischium close to the symphysis pubis crossing the medial lesion of the obturator foramen. One year later Hopf published a technique that allowed all three osteotomies to be performed through a single Smith-Petersen approach. For more cephalad dislocations, Hopf recommended the osteotomy go through the floor of the true acetabulum, osteotomizing both the ilium and the ischium together. This was in concept a triple osteotomy done by a double osteotomy. But as the osteotomy puts the vascularization of the acetabulum at risk, there was concern of osteonecrosis of the graft . Steel’set al. [et al. [Tönnis et al.  and Carl [et al.  addresseet al. [Four long-term reports have reviewed the results of follow-ups that are more than a mean of 11 years  Table I. Dungl eet al.  reportedet al. [et al. [Jannsen et al.  assessed [et al.  assessedIt is an invasive surgery. There is increase of the weight bearing area of Hyaline cartilage. The movability of the graft is much improved but still constrained and obtaining optimal coverage and medialization can be difficult. The osteotomy is unstable needing postoperative immobilization. Besides the Hopf technique, the blood supply to the graft is stable, considerable deformity of the pelvic ring is expected in cases with large corrections. The level of dysplasia that can be treated can be limited .It is an invasive surgery. Weight bearing area of Hyaline cartilage is increased. The movability of the graft is much improved. The osteotomy is unstable needing postoperative stabilization. The blood supply to the graft is stable. Considerable deformity of the pelvic ring is expected in cases with large corrections. The level of dysplasia that can be treated is good .Spherical periacetabular osteotomies include the Spherical osteotomy described by Wagner , the DiaEven though the surgery is highly advantageous when considering the ability to reposition the acetabulum, there are a few inherent drawbacks of the surgery that must be considered. Because of the proximity of the osteotomy to the joint medially and distally, part of the osteotomy is actually intra-articular, which makes the vascular supply to the acetabular fragment reliant on the vascularity through the undamaged hip joint capsule, making it difficult to explore or treat pathology inside the joint . FurtherThough there have only been a few long-term reports on the spherical and dial osteotomies , 35. TheWe identified six studies , 42–44 rThe mean preoperative center edge (CE) angle ranged from −1.7° to 3° and postoperatively 35° to 43°. The preoperative severity of the CE angle did not significantly influence any of the results. Negative factors influencing the results of the RAO were a higher age, the degree of osteoarthritis and not being a congruent joint at the time of surgery. The congruency of the joint was confirmed by the ability to obtain good congruity in the hip abduction position.There have also been many reports from Japan , 44–46 sOverall, the long-term results of the RAO in these series were excellent, and the complication rates, particularly of fragment vascularization related problems, were low. However, there have been other reports of a high rate of acetabular graft necrosis and chondrolysis after RAO . The conAll of the excellent long-term results of RAO have come from Japan; there is a possibility that the small stature and lighter weight of the Japanese and also the strong negativity toward prostheses at a young age in the Japanese culture may have influenced some of the results.It is an invasive surgery. Weight bearing area of Hyaline cartilage is increased. The movability of the graft is good. Medialization of the join is restricted. The osteotomy is stable. The blood supply to the graft is a concern. The pelvic ring is maintained. The level of dysplasia that can be treated is good .. Since then many surgeons have advocated variations of the surgery. For the skeletally immature patients a technique more similar to an acetabuloplasty has been used [et al. [The Shelf operations were designed to increase coverage of the femoral head by constructing an extra-articular bony buttress extension of the slope of the acetabulum, and was first described by Köng . Since teen used   preoperatively had a good clinical result at a mean of 23.8 years follow-up. The mean preoperative and postoperative CE angles were −0.089° (SD 14.8) and 40.3°, respectively. They also determined that the Shelf height was significantly lower in the group with good results compared with the group with poor results. Hirose et al. followed 28 patients with a mean preoperative and postoperative CE angles of −4° (−27° to 20°) and 38° (13° to 60°), respectively, and observed a survival rate of 80% at 25 years, but their follow-up rate was low at 49%. Bartoníček et al. reported in a subgroup of 20 patients with a mean preoperative and postoperative CE angles of 16° (−15° to 20°) and 32° (25° to 45°), respectively that had a spherical, concentric hip without osteoarthritic change before operation had a survival rate of 94% at a mean follow-up of 14 years.Studies which reported on a more homogenous group of patients, where patients’ mean age were over 12 years old with a minimal amount of osteoarthritic change, the results have been good , 69–73 . It shou [et al.  and Bart [et al. , each reJudging from the literature, good long-term results can be expected with the Shelf operation and best results may be expected in the young adult with a dysplastic spherical centered hip without osteoarthritic changes. The Shelf operation still has to be considered as a treatment option for the dysplastic hip as long as the indications are thoroughly considered.It is considered to be one of the least invasive surgeries, though the damage to the abductors is a concern. The weight bearing area of Hyaline cartilage cannot be increased. The acetabular joint is not moved. Medialization of the joint cannot be done. The Shelf is stable. The osteonecrosis of the acetabulum is not a concern but resorption of the graft can occur. The pelvic ring is maintained. The level of dysplasia that can be treated is controversial .In the early 1950’s Dr Chiari realized that patients with DDH that had subluxation and/or advanced stage osteoarthritis suffered unsatisfactory results with the Shelf procedures. He indicated that any persistent subluxation after a Shelf operation caused an insufficiency of the gluteal muscles because of the lateralization of the femoral head. To exclusively treat these difficult cases he introduced his medial displacement iliac osteotomy. The osteotomy was introduced in Vienna in 1953, but was only reported in the English literature in 1974 . The basThe surgical advantages are the abnormally lateral position of the hip is overcome, and load upon the hip is reduced through medial displacement. In addition remodeling of the new acetabulum in the postoperative years adds substantially to the area of support for the femoral head as the surface formed at osteotomy becomes more closely applied to the capsule. The operation can accommodate a significant degree of acetabular migration , 75.The Chiari osteotomy historically has been used as a salvage surgery. The indications from the literature are vast; the age indication is from children over the age of 4 with no upper age limit, congenital subluxation of the hip, Coxa magna after Perthes’ and dysplastic hip with or without osteoarthritis.et al. [There have been many series reporting the long-term results of the Chiari osteotomy, and all have shown good results , 76–81. et al. . They reet al.  Fig. 1). et al. [et al. [et al. [et al. at a mean follow-up of 11.3 and 20.4 years, respectively. These authors noted that excellent correction was maintained, and the hip joint was preserved in 87.6% at 10 years, 77.3% at 15 years and 60.5% at 20 years. Several factors were associated with an unfavorable outcome, including older age of the patient at the time of the surgery, moderate to severe preoperative coxarthrosis, an associated labral lesion, less anterior coverage correction and a suboptimal postoperative acetabular index [et al. [The preliminary surgical results with this technique were first reported by Ganz et al.  in a mix [et al.  and Step [et al.  have up ar index . The onlet al. [Clohisy et al.  have indIt is an invasive surgery. Weight bearing area of Hyaline cartilage is increased. The movability of the graft is good. Medialization of the join is a feature of this osteotomy. The osteotomy is stable. The blood supply to the graft is good. Deformity of the pelvic ring is limited. The level of dysplasia that can be treated is broad, but does have its limitations .In this manuscript, the authors’ assessed the relative abilities of the various described procedures in achieving ideal goals and characteristics of a procedure for the treatment of hip dysplasia, and have summarized the results in This article describes the evidence-based indications for the different osteotomies described for DDH in As this was a review of the long-term results of each surgery, we were not able to assess the differences between surgeries in their immediate postoperation rehabilitation phases, where in modern day treatment minimal invasiveness and short-term rehabilitation has become an emphasis. In the modern era the demands and standers of the patient and the surgeon have drastically increased, as improvement in not only pain but also restoration of an active physical life is desired. The THA prosthesis and surgical techniques have also improved making the emphasis on the longevity of the initial joint preservation surgery not as important a factor as it may have been in the past. We understand these changes in the meaning of what a successful surgery is make it difficult to compare the results of past surgeries to present standards. Even though the endpoint of the surgery may differ, assessing their long-term results still gives us an assumption as to how long the patients were relatively satisfied with their surgery. We believe it is meaningful to assess the many surgeries of our predecessors and see how their results have done over a prolong period of time and by doing so hopefully open the possibility to new techniques or ideas for improvements in the future.This review has focused on the long-term results of augmental osteoplasties and pelvic osteotomies, other than the PAO, that have been used to treat the dysplastic hip in the skeletally mature patient. From its characteristics, the Bernese PAO would be the surgery of choice for this entity. However, many surgeons have shown other surgeries such as the Shelf operation, RAO and Chiari osteotomy have proven over time that when the indications are correctly met and surgery is conducted properly excellent to good results can be expected even in the long-term, and can still be considered to have a place in the treatment of hip dysplasia.None declared.


An obstacle for precision improvement in quantum metrology is the information loss causing by the unavoidable interaction between probe system and environment. Quantum fluctuations are environment no system can be isolated from and it will make the precision of initial parameter estimation of the probe atom decrease with time. After the typical time of the spontaneous decay of the probe atom, the precision is greatly damaged. However, quantum fluctuations can be modified. Our results show that if we put several ancillary atoms beside the probe atom in symmetrical arrangement, the probe atom will be affected by the ancillary atoms indirectly and the information loss of the probe atom causing by the quantum fluctuations will be partially avoided. We find that the retained precision after long time evolution can approaches to  Fisher information is used to describe the precision limit and it has been extended to quantum regime. The so-called quantum Fisher information (QFI) is used to describe how well one can estimate a parameter from a quantum state4. Since the central task in quantum metrology is to improve the precision of parameter estimation, how to increase the QFI in quantum state becomes a key issue in quantum metrology. Initial correlated systems such as entangled states have been used to increase the QFI in comparison to that in case of using initial uncorrelated systems, thus improve the precision limit of parameter estimation19. However, in reality, the probe systems are unavoidably in interaction with the environment, the quantum decoherence caused by the environment may decrease the QFI as well as destroy the quantum entanglement in the probe system exploited to improve the precision. In this regard, the dynamics of the estimation precision induced by the interaction between different models of system and environment have been studied39. As a result, how to control the environmental effects on quantum metrology becomes an important issue.In estimation theory, parameter can be estimated from probability distribution and the Cramér-Rao bound40. However, quantum fluctuations can be modified. If we put several ancillary atoms beside the probe atom, since all atoms are in interaction with the quantum fluatuations, the probe atom will be affected by the ancillary atoms indirectly and the information loss of the probe atom causing by the quantum fluctuations will also be modified. As the indirect correlations of atoms are determined by the relative arrangement of the atoms, we may wonder what kind of arrangement will help us reduce the information loss and how much will the precision be retained.In quantum sense, quantum fluctuations are environments which no system can be isolated from. The interaction between quantum fluctuations and a probe atom will cause the decoherence behavior of the probe atom. Thus the precision limits of estimating initial atomic parameters decay with time and after the typical time of the spontaneous decay of the probe atom, the precision is greatly damagedN − 1 identical two-level ground state atoms interacting with a bath of fluctuating scalar fields in the Minkowski vacuum. We use the natural units and the total Hamiltonian of such a system can be written asσ0 being the 2 × 2 unit matrix. We assume all atoms have the same energy level spacing ω0. HF denotes the Hamiltonian of the scalar field and the interaction Hamiltonian HI is taken in analogy to the electric dipole interaction in the weak coupling limit asμ denotes the coupling constant. We consider the probe system (atom 1) and an ancillary system consisted of ϕ of the state of the probe system. So the total state of the probe system, ancillary system and environment at initial time can be written asWe assume the parameter to be estimated is the phase factor e1〉, |g1〉 denote the excited and ground state of the probe atom. |gelse〉 denotes the direct product of vacuum states of all the other atom. We assume the total state at time t has the formHere |t = t − t′.Applying the above equation into the evolution equation of the total state (4), we haveN = 2, which means the ancillary system contains only one ground state atom and we use L to denote the distance between the two atoms. In this case, the initial state of the total system reduced toAt first, we let t becomesThe state at time b1(t) and b2(t) becomeA = C11 = C22 and B = C12 = C21. So we haveAs a result, the evolution equations of A and B are determined by the Fourier transformation of the field correlationsThe coefficients X from the atomic state ρ(X), there exists an uncertainty of the parameter X, which satisfies the uncertainty conditions4N represents the repeated times and FX denotes the quantum Fisher information of parameter X, which has the form38Then the Bloch vector of the probe atom in Schrodinger picture can be written asApplying Eq.  into theγ12 → γ0. As a result, due to the existence of the second term, the QFI may partially protected when γ0 is the spontaneous decay rate). In reality, the small distance condition can be fulfilled by using long-wavelength molecule. In international system of units, taking LiH whose vibrational transition frequency is ω0 = 4.21 × 1013 Hz as an example, distance of z = 1 μm satisfies zω0/c = 0.1441.We find that the QFI depends on the distance between the two atoms. When N = 3. In three atoms case,Now we let From Eq. , we havem + n = −1. As a result, we haveIn order to have the protection term in QFI, we need B = C, in order to have a solution in Eq. t( part has the same weight with that in two atoms case. So the protection part in QFI is same with that in two atoms case and the retained QFI becomes one quarter of the initial QFI. In conclusion, in three atoms case, the QFI can be partially protected and the largest retained QFI is obtained in condition that the three atoms are in symmetrical arrangement that the distances between all of the two atoms are same.As a result, the N atoms. We assume the distance of each of the two atoms is same and the distance is small compared to the transition wavelength of the atoms Since the largest remained QFI is obtained in the above symmetrical arrangement, now we expand this well arrangement to As a result,SoSolving the above equations, we haveThe Bloch vector of the probe atom is obtained asSo the QFI can be calculated asN = 4 at most. In this case, the probe atom and the three ancillary atoms are located in the vertex of regular tetrahedron as is shown in Fig. (Due to the second part of the above equation, the retained QFI becomes N − 1 two-level ancillary atoms. Our results show that the QFI, thus the precision limit of the estimation of probe atom will be retained after long time evolution with proper arrangement of the atoms. The largest retained QFI is obtained in symmetrical arrangement that the distances between all of the two atoms are same and the retained precision approaches to N = 4 at most.In conclusion, we have studied the dynamics of QFI of parameters of initial state of a static two-level probe atom in the Minkowski vacuum in the existence of


The temporal transcription factor Krüppel has a dual role in the development of neurons. Related research article Stratmann J, Gabilondo H, Benito-Sipos J, Thor S. 2016. Neuronal cell fate diversification controlled by sub-temporal action of Kruppel. eLife5:e19311. doi: 10.7554/eLife.19311A neuronal stem cell is a cell that divides to produce another neuronal stem cell plus a cell that can go on to become any one of the different types of neurons or glial cells that are found in the nervous system. Understanding how this happens is a major challenge in developmental neuroscience. In both vertebrates and invertebrates, the capacity of neuronal stem cells to produce specific cell types is determined by a combination of spatial patterning factors, essentially determined by their birth location, and temporal patterning, in which transcription factors that are expressed sequentially in the neuronal stem cells determine the kind of cells that are produced during a given time window . This receptor normally inhibits the expression of a transcription factor called Collier: however, the inhibition of Svp allows for the establishment of a feedforward loop downstream of Collier that leads to the expression of the neuropeptide Nplp1 and the establishment of Tv1 neuron identity .As the neuroblast divides to produce Tv2 and Tv3, Svp and two other proteins – Squeeze (Sqz) and Nab – are expressed: this all leads to the inhibition of Kr and the repression of Collier. As a consequence the Nplp1 feedforward loop is inhibited and the default Ap/Eya identity in Tv2/3 is established. In the last division, as the neuroblasts gets ready to switch to the next temporal window, the increased expression of Grainyhead  has two effects: it promotes the expression of a neuropeptide called FMRFa, and it helps to inhibit Svp expression. The end result is to prevent the establishment of the generic Tv2/3 fate to promote the Tv4 identity. However, Grainyhead cannot inhibit Svp on its own, so another factor must also be expressed during this period to help it repress Svp .The implications of these observations extend well beyond the details of the NB5-6 lineage and raise additional questions: How is Kr and Sqz expression scheduled? And how is Nab expression delayed to only be present in Tv1? Such delay could be explained by the formation of a feedforward loop in which Castor and Sqz combine to promote Nab expression . The facMany of the factors that are active during the Castor window are also active during other windows. As we have seen, Krüppel is active in neuroblasts during the Kr window and is active again in Tv1 neurons produced during the Castor window. Sub-temporal factors can also have multiple roles: Svp, for example, is expressed early in neuroblasts to regulate the transition from the Hunchback window to the Krüppel window , and is The expression of Collier requires the input of several spatial transcription factors , but thi


An in-depth analysis of the method employed to release and deliver the medication is described and a series of experiments is presented which validates the drug delivery system. The results show that a variable pitch conical compression spring manufactured from stainless steel can deliver 0.59 N when it is fully compressed and that this would be sufficient force to deliver the onboard medication.This paper reports a novel medication release and delivery mechanism as part of a next generation wireless capsule endoscope (WCE) for targeted drug delivery. This subsystem occupies a volume of only 17.9mm Endoscopes and colonoscopies are used routinely by gastroenterologists to diagnose and treat pathologies such as Crohn’s disease in the gastrointestinal (GI) tract. However the small intestine poses a problem for these conventional methods as it is very difficult to access. One method employed to overcome this problem is the use of wireless capsule endoscopes (WCE). These pill-sized cameras take pictures of the intestinal wall which are then used to diagnose pathologies. The market leader in WCE is Given Imaging Ltd.  who in 2The problem with current WCE devices is that they do not offer the ability to administer therapy to an affected area of the GI tract. However there is a clinical need to target and treat these pathologies  hence enThe focus of conventional passive WCE medical devices has been to take pictures of the GI tract however the next generation of WCE must possess additional functionality to enable them to carry out useful tasks such as performing a biopsy or targeted drug delivery . To faciThe limitations of conventional WCE have led researchers to explore methods of increasing a capsule’s functionality such as the ability to navigate through the GI tract –5 or resMenciassi et al. (2005)  propose A major limitation of commercial WCEs is the lack of control over their speed and direction of travel as they rely on the natural movement from peristalsis to progress through the GI tract. A potential solution to this issue is the robotic legged locomotion device developed by Valdastri et al. (2009) . The 12-Inspecting the lining of the oesophagus is routinely performed using a flexible endoscope however this procedure results in discomfort for the patient. An approach proposed by Tognarellia et al. (2009)  utilisesPhaeton Research has developed the Enterion capsule  for the The InteliSite capsule manufactured by Innovative Devices LLC  deliversThe IntelliCap is an intelligent pill developed by Philips Research  to electKarargyris et al. 2015)  propose 15  propoIt is of great benefit to know the position and orientation of the WCE when it is travelling through the GI tract  as the 3The InteliSite capsule  can be tThe position of the M2 A by Given Imaging  is deterA promising method to monitor the movements of a WCE through the GI tract is through the magnetic field strength of an onboard permanent magnet . MagnetoThe aim of this research is to increase the capability of passive capsules by increasing their functionality, specifically to achieve targeted drug delivery in the GI tract. Our previous work focused on developing a mechanism to resist natural peristalsis and also to target specific locations in the GI tract. A novel biologically-inspired holding mechanism was proposed which is based on the order of insects known as Coleopterans (beetles). Coleopterans have two pairs of wings and include insects such as the coccinellidae (ladybird). The ladybird has the ability to fold away its wings behind a second hardened pair of wings which are used as a casing to protect them. Using the concept of a pair of folded wings protected by an outer case as a basic premise, a compact holding mechanism was prototyped from Nylon 6 and incorporated into a WCE for the purpose of resisting natural peristalsis in the GI tract . To furtThis paper presents the final mechanism required for targeted drug delivery in the GI tract. A method of delivering medication from the microrobot’s onboard reservoir to a site of interest in the small intestinal tract is presented which, combined with the holding mechanism and targeting mechanism, results in a microrobot with sufficient functionality to deliver a metered dose of medication to a target site in the GI tract. The paper is organised as follows: Section The clinical need to treat pathologies of the GI tract are not being met by today’s technology. Currently pathologies such as Crohn’s disease and ulcerative colitis are being treated by conventional endoscopes in the lower section of the alimentary canal however the middle section of the GI tract, the ilium and jejunum, can only be accessed by the application of a WCE. Images transmitted from a WCE are reviewed to diagnosis pathologies however these passive devices are limited as they are not capable of administering curative treatments. Figure Figure The holding mechanism in Fig. Delivering a metered dose of medication to a site of interest is achieved through a novel mechanism utilising a cam, a needle funnel, two opposing ratchets, a needle and a single micromotor manufactured by Namiki. Orientating the micromotor along the central axis of the microrobot allows for simple coupling to the cam and needle funnel via two opposing ratchets. Driving the micromotor anticlockwise allows for the angular positioning of the needle, which has been fixed at one of 16 positions equally spaced. Driving the micromotor clockwise extends and retracts the needle. The novel positioning mechanism functions through the use of a series of ratchets engaging and disengaging to allow the various operations to be performed. A detailed evaluation of the targeting mechanism can be found in . Figure The drug delivery system has the capacity to store a 1 ml volume of medication onboard the microrobot. The force generated by a compressed conical spring is proposed to expel the medication. The conical spring engages with a piston and when activated it will force the medication out of one of sixteen preset holes at the base of the medication chamber. The holes have a thin membrane across them to protect the integrity of the medication and to prevent the medication from leaking into the needle positioning mechanism. Rotating the needle positioning mechanism will align a port on the back of the needle funnel with one of the sixteen holes, the remaining holes would automatically be blanked off and therefore prevent any ingress of the medication. The novel configuration of the conical spring provides a compact design however a triggering mechanism will also be required to automatically release the spring.The following sections discuss the design and analysis of the drug delivery system, the trigger mechanism and the issue of power distribution through the microrobot. A series of experiments are presented which validate the drug delivery system.Using a compressed spring to drive the delivery of the medication would require allocating a volume of space within the microrobot for the spring’s solid state volume and for the spring’s actuation mechanism. A novel way of minimising the spring’s volume is to use a conical compression spring, Fig. 3 this can be compared to a volume of 55.0 mm3 for a conventional compression spring with the same geometry. Providing clearance between the coils enables them to be spiralled inside each other. A variable pitch is required between each coil to allow the spring to collapse at the same rate, this is due to the larger coils collapsing faster than the tighter coils. This configuration allows the active coils to bottom simultaneously resulting in a straight line force versus deflection curve similar to the output of a conventional compression spring. To release the spring from the compressed position a trigger mechanism will be required.Figure The conical compression spring will require analysing to determine the optimum medication delivery force. This will involve analysing a number of spring variables such as the number of coils, the diameter of the wire and the force required to operate the system. All these factors will influence each other’s performance and a balance will need to be determined which will minimise the space required to house the system.To deliver a 1 ml volume of medication to a target site requires the onboard supply of medication to be pushed through a series of holes allowing it to be expelled through the needle tip. To achieve this task an evaluation of the force required to expel the medication must be performed. The bore of the needle is the most restrictive section of the delivery system for the flow of medication. The needle has an internal diameter of 0.38 mm and a length of 6.7 mm. As the needle has a consistent diameter and length Poiseuille’s equation can be used to model the flow of medication through the needle. The assumptions which will be made with Poiseuille’s equation are that the medication is incompressible and Newtonian, the flow is laminar and friction will be ignored .The flow rate of a needle r is the radius of the needle’s bore, nv is the viscosity of the medication and l is the length of the needle. P2 is the pressure required to expel the medication. For the purpose of analysis the viscosity of the medication will be based on water at 36 °C (0.705 × 10−3 Pa s). Where 2.6 kPa) .As the medication must be absorbed by the subcutaneous tissue a delivery time has been set at 3.5 s. The flow rate  based on a solid length of Using an input force of 0.43 N and a combination of 0.25 mm diameter wire, 7.5 active coils, a mean coil radius of 2.1 mm for the first coil and a mean coil radius of 5.0 mm for the final coil results in a spring with a free length deflection of 49.7 mm and which only occupies a volume of 17.9mmThe increased spring deflection results in a new starting force −2 of stress induced in the compressed spring. The requirement for the spring is for a single operation therefore the maximum allowable static stresses would be limited to 59 % of the material’s ultimate tensile strength  [The 0.59 N force which is generated by the spring at the start of the stroke results in 915.2MNm00MNm−2) . The resTo deliver the 1 ml volume of medication a trigger mechanism is required to release the compressed conical spring. Releasing the spring remotely at the required moment in time is a challenging requirement. The system chosen to release the spring is a thermo mechanical method. This method of triggering the spring relies on the Joule’s effect to heat an igniter which in turn ignites a pyrogen that melts a Nylon wire. The Nylon wire is employed to retain the compressed coiled spring. Figure Figure −2 and a diameter of 0.10 mm. The technology chosen to ignite the propellant, which in turn will melt the Nylon wire, is an electro-pyrotechnic initiator thin film chip (EPIC) . The microjoule energy device is a surface mount device (SMD) (size 0603) comprising a ceramic  based substrate with a tantalum nitrogen (Ta2N) deposit as the activating resistor. A propellant, which ignites at 456.8 °C [The compressed conical spring will be delivering a load of 0.59 N at maximum compression therefore the Nylon wire must be capable of holding this force without breaking prematurely or elongating under the strain and partially delivering the medication. A Nylon monofilament wire has been selected which melts at 220 °C, has a Young’s modulus of 3,300MNm456.8 °C , is applThe resistance l is the length of the heating element, w is the width and t is the material’s thickness.Where l), 50 μm for the width (w) and 2 μm for the thickness (t) results in a heating element resistance Ei) required to ignite the propellant and melt the Nylon wire can be calculated by the following formula:Using the geometry of 75 μm for the length , −1 °C−1) and Where Using equation  with theequation  results The firing time Where Using equation  with a sThe microrobot presents a number of challenges to realising a system which can perform targeted drug delivery as limitations on space restrict the use of components, however the various electronic components and wiring must be considered. The key electronic components will include the following:CMOS Image Sensor: This design uses a commercially available subminiature image sensor manufactured by Toshiba (TCM8230MDA) with four white SMT LEDs manufactured by Agilent (HSMW-C191) integrated on a PCB.Controller ASIC: The power management , telemetry, timing and control are being implemented in a full-custom ASIC in a commercially available 0.18 μm CMOS technology. Much of the specific circuit implementations will be based on previously reported systems –35.System Wiring: The increased functionality the mechanisms bring to the microrobot present the challenge of supplying power to the actuators performing the various operations. A circuit schematic of the power distribution for the microrobot is presented in Fig. The visualisation and processing sectionThe holding mechanismThe needle positioning mechanismThe medication delivery systemThe power supply sectionFigure The configuration of the five sections of the microrobot presents problems of power delivery through the device, specifically delivering power to the holding mechanism and the visualisation and processing sections. This is due to the requirement that the holding mechanism can be deployed diametrically opposite the needle. This feature requires the front section of the microrobot to rotate 360° relative to the rear section. It is assumed that the rear section will remain static due to the mass of the medication and power supply and also from the pressure generated by the GI tract wall. The needle positioning mechanism and the medication delivery system have direct access to the power supply, however the medication chamber and the micromotor driving the needle positioning mechanism inhibit the direct passage of power to the front of the microrobot. Figure To overcome the issue of power distribution through the microrobot and to control the angular orientation of the needle positioning mechanism a specifically designed rotary encoder is proposed.A specifically designed rotary encoder mounted between the medication chamber and the needle positioning mechanism is the proposed solution for providing power through the forward section of the microrobot, Fig. The rotary encoder board, which is 0.5 mm thick, allows power to be supplied to the visualisation and processing section and to the holding mechanism while the front of the microrobot is rotating. The rotary encoder achieves this through four 0.3 mm wide concentric tracks which have been positioned to take into consideration the limitations of flexible PCB manufacture and also to accommodate the holes which allow the medication to pass through the board and into the needle funnel, Fig. a. ContacThe contact pins align with pads on a flexible PCB board which is incorporated into the needle funnel. The pins stand proud of the needle funnel by 0.05 mm to ensure they make contact with the tracks on the rotary encoder board. The flexible PCB passes through the needle funnel and through the retaining plate.The shape of the distal end of the holding mechanism’s legs have been designed to accommodate the flexible cable, however the cable cannot pass through the bevel gear set which is positioned behind the holding mechanism’s legs as it will be rotating. Therefore the power supply is again routed out through the side of the microrobot and then back into the space behind the bevel gear set where it can supply power to the visualisation and processing section and to the holding mechanism.The power supply for the forward section is supplied through the onboard battery which is stored at the rear section of the microrobot. As specified the rotary encoder’s flexible PCB board adheres to the outside of the microrobot’s body and connects to the power supply, however the power supply is required to be removable to allow access to the medication chamber for loading.A compact method of connecting the power supply to the microrobot is required which will allow access to the medication chamber for filling and also connect with the flexible PCB board which links to the rotary encoder. Figure Figure The proposed solution allows the medication chamber to be manually filled at the point just prior to administration. This feature gives flexibility in the choice of medication which can be prescribed to the patient therefore potentially broadening the scope of its use.3 and an energy density of 435 Wh/L (CR1025 Energizer), the mechanisms will consume at most 28.94 J of energy for each complete cycle which is only 9.83 % of the available energy, offering the potential for multiple operations.The design of the modular battery unit allows power to be supplied to the mechanisms of the microrobot. As the onboard space to hold the power supply is limited a review of the power consumption of the various mechanical mechanisms has been performed. The energy required to operate the trigger mechanism is very low at only 55 μJ however the energy required to operate the needle positioning mechanism and the holding mechanism is much greater. The energy required to operate the two mechanism has been estimated from the peak current consumption of the Namiki motor controller (SSD04) and the Faulhaber motor controller (BLD05002S), which are stated as 800 mA at 6 V and 400 mA at 7.5 V. Three revolutions of the Namiki micromotor are required for positioning and deployment of the needle; this is achieved in 3.8 s, while the holding mechanism can complete a full opening and closing cycle in 1.78 s. Using a Lithium coin battery with a volume of 188mmThis section presents a series of experiments designed to validate the medication delivery system. The experiments focus on determining the parameters required for the delivery of the medication and on the performance of the conical compression spring through quantitative assessment of a 1:1 scale model prototype manufactured from stainless steel (BS 2056 Austenitic 302).−3 Pa s to compensate. The implication of this change will be a reduction in delivery speed to 5 s to maintain the calculated delivery force.The purpose of the medication performance experiment is to determine if the chosen delivery speed of 3.5 s is suitable to expel the 1 ml of onboard medication. The analysis performed in Section The test set-up used to measure the delivery force required to expel the 1 ml of medication is presented in Fig. a. A specThe mathematical model Eq.  presentei (805–102) test system manufactured by Mecmesin to measure the load required for a delivery. The loadcell has been programmed to travel at the required delivery speed of 207 mm/min for a distance of 17.20 mm from the tared zero position. A computer running Emperor™ (force) software (v. 1.18–408 (5/10/13)) is connected to the MultiTest system and used to record the delivery data.Figure The delivery program will be run multiple times with no liquid being delivered and the data for each run recorded. The results of the average delivery force will be combined and the average of these runs will be used to calculate the friction in the system due to the seal on the plunger. The syringe will be filled with water and a piece of chicken breast flesh positioned such as the needle tip is embedded into the chicken by approximately 1.5 mm. Chicken breast flesh has been chosen as it has significant similarities to the tissue of the GI tract wall . The delMeasurement of the force required to operate the plunger assembly with the luer lock and needle fitted were first taken to establish a baseline friction force for the plunger assembly. Due to the sensitivity of the measuring system and the variability of the results a large number of deliveries were performed. Over a set of 30 runs the average delivery force for a dry delivery was 2.3 N.A series of deliveries were performed which expelled a 1 ml volume of water with the needle orientated in the vertical configuration and also with the needle orientated in the horizontal configuration, as this would more closely match the needle orientation in the microrobot. The needle configurations can be seen in Fig. The average delivery force for a 1 ml volume of water over 10 runs for the vertical configuration was 2.75 N, this can be compared to the average delivery force for the same volume of water over 10 runs for the horizontal configuration which was 2.73 N. The results show that the average horizontal delivery force is lower than the vertical delivery force. The small difference in delivery force (17.0mN) can be attributed to the sensitivity of the test method. However the results confirm that there is very little turbulence in the system and hence confirms the low Reynolds number and that the flow will be laminar.A series of deliveries were performed which expelled a 1 ml volume of water into chicken breast flesh to simulate the intestinal pressure at the end of the needle tip. The needle was orientated in the vertical configuration as it guaranteed needle penetration and prevented the chicken breast flesh from being pushed away from the needle due to the pressure of the delivery force. The set-up used to measure the delivery force can be seen in Fig. An overlay of the measured load profiles for three deliveries of a 1 ml volume of water into chicken breast flesh can be seen in Fig. The test result plots highlight the behaviour of the delivery method, for example a spike of 4.0 N can be seen in sample 3 at the beginning of the delivery Fig. . The spiTo deliver the medication in 5 s the variable pitch conical compression spring must be capable of providing the calculated force of 0.59 N at the start of the delivery. Therefore the design of the spring must be validated to ensure its suitability to perform the task. There are no British Standards or industry standards for the design of conical compression springs however The Institute of Spring Technology (IST) provides a software package which is based on theoretical mathematical models and empirical data to aid in the design and analysis of conical compression springs and also to determine their suitability for manufacture. The IST software will be used to verify the calculations derived in Section The space available onboard the microrobot to house the spring has changed due to the requirements imposed by the trigger mechanism therefore the spring parameters will be modified from those used on the theoretical mathematical model Eq.  to accom−2 has been selected for the prototype spring. The 0.25 mm diameter wire has 7.5 active coils, 2 dead coils for the purpose of stabilising the spring during operation, a mean coil radius of 2.6 mm for the first coil and a mean coil radius of 5.12 mm for the final coil and a free length of 48.8 mm. The modified spring parameters result in a linear spring rate of 10.9mN/mm which equates to a theoretical solid state load of 0.53 N however the software predicts a solid state load of 0.79 N and a solid state stress of 991.0Nmm−2 (45 % of UTS). The discrepancy in load can be attributed to one of the coils prematurely touching at the final stage of compression, this will result in the coil collapsing which in turn will increase the spring rate. However it is anticipated that manual modification of the spring end will eliminate this issue and result in the calculated load (0.53 N).A stainless steel wire spring (BS 2056 Austenitic 302S26 G2) with a module of rigidity value of 70.3GNmThe stainless steel conical compression spring will be mounted on a mandrel and held between two supports which have been designed to hold the end coils in position while the spring collapses. The test set-up used to measure the force delivered by the compression of the conical spring is presented in Fig. i manufactured by Mecmesin. A 2 N loadcell  will measure the load generated by the compression of the spring from its free state to its solid state. The test will be run at a velocity of 145.0 mm/min which matches the calculated delivery speed. The compression program will be run multiple times with the data for each run recorded. The results of the average peak force at solid state will be combined and the average of these runs will be used to calculate the delivery force. A further measurement at 12.0 mm deflection will be recorded and the average force from the deliveries will be used to determine the spring’s force at the end of its stroke.The spring will be tested on a MultiTest 2.5-A total of 10 springs were dimensionally inspected on a digital vision measuring system  with the results showing that the 2.6 mm mean coil radius for the first coil was outside of the design specification at 2.76 mm and the springs’ free length was 47.7 mm compared to the design value of 48.84 mm. The reduced clearance between the coils due to the larger radius of the first coil resulted in the coils touching during the final stages of compression. The coils could not be manually modified to reinstate the clearance as initially anticipated therefore the springs were tested through a stroke length of 46.65 mm to minimise the impact of the coils colliding. Figure The test jig was configured such that the mandrel could pass freely in and out of the loadcell adaptor without generating a false reading on the loadcell due to friction. A 0.5 mm by 10.3 mm diameter counter bore was positioned in the loadcell adaptor support to accommodate the large coil and to prevent it from moving during compression. The 0.5 mm depth of the bore allowed clearance for the coils at the end of the stroke. Figure A total of 10 springs were compressed 10 times each from a preloaded compression of 0.2 mm through a stroke length of 46.45 mm to give a total working compression of 46.65 mm. The stroke length allowed 1.05 mm of clearance at the end of the stroke for the solid state of the spring. The springs were preloaded to stabilise the coils during the compression sequence and to accommodate slight variations in the overall length of the spring. A typical load profile of a spring compression can be seen in Fig. Figure It is a requirement that the spring can deliver a force of 0.43 N at the end of its 12.0 mm stroke to guarantee delivery of the medication in 5 s. It can be seen in Fig. 3.In this paper we have presented the first WCE with increased functionality to allow targeted drug delivery to be performed in the small intestinal tract. A novel drug delivery system has been proposed which delivers 1 ml of medication and only occupies a volume of 65.0 mm3. The conical spring is capable of delivering a force of 0.59 N at the solid state and a force of 0.43 N at the end of the 12.0 mm stroke which is sufficient force to expel the 1 ml of onboard medication in the required delivery time of 5 s.It has been shown through analysis and experimentation that a stainless steel variable pitch conical compression spring can be wound such that it has a solid state thickness of the wire diameter and occupies a volume of 17.9mmThe presented solution for targeted drug delivery combines a holding mechanism capable of resisting peristalsis, a targeting mechanism capable of positioning a needle within a 360 degree envelope and a medication delivery system and integrates them into a conventional wireless capsule endoscope. The combined mechanisms only occupy 75 % of the available volume including the 1 ml of medication and the power supply.


Deep inspiration breath‐hold (DIBH) is a technique for treating left‐sided breast cancer (LSBC). In modern radiotherapy, one of the main aims is to exclude the heart from the beam aperture with an individualized beam design for LSBC. A deep inhalation will raise the chest wall while the volume of the lungs increase, this will again push the heart away from the breast to be treated. There are a few commercial DIBH systems, both invasive and noninvasive. We present an alternative noninvasive DIBH system based upon an industrial laser distance measurer. This system can be installed in a treatment room at a low cost; it is very easy to use and requires limited amount of training for the personnel and the patient. The system is capable of measuring the position of the chest wall with high frequency and precision in real time. The patient views its breathing curve through video glasses, and gets instructions during the treatment session. The system is well tolerated by test subjects due to its noninvasiveness. Invasive instruments are not always well tolerated, and some of them use an indirect way of visualizing the motion of the chest wall. The Real‐Time Positioning Management system  is less invasive and relies on a box with infrared markers that is placed on the patient's xiphoid process. The position of the box might vary from day to day, and its placement can influence the patient positioning and could increase the dose to the skin if placed within the field borders due to the build‐up effect.In this technical note, we present a laser distance measuring system that tracks the motion of the sternum with high precision and frequency. It is possible to install the system in the clinic at a low cost, and it is very easy to use with limited training needed. The method is noninvasive, and causes no discomfort to the patient. The patient views the tracking of the sternum through video glasses. We also compared our laser system to the Catalyst surface scanning system in order to investigate if the laser system could be used as reference system for Catalyst treatments, and if the in‐house system could also be used interchangeably with the Catalyst system.Our main aim was to develop a DIBH system and evaluate its performance. Secondly, we would like to investigate the interchangeability with the Catalyst system.2The respiratory gating system utilizes a FLS‐C10 laser distance measurer , which is an optical distance measuring device that measures absolute distances on natural and reflecting surfaces. The laser distance sensor has an absolute accuracy of ± 1 mm @ 2σ and a repeatability of typically ± 0.3 mm @ 2σ with a measuring rate of 10 Hz in normal operation, where σ is the standard deviation. The laser distance measurer is connected to a computer via a RS‐232 serial interface and an in‐house developed program in Visual Basic  is used to interact with the laser, store data, and visualize the breathing curve with a small smoothing . The operator is able to adjust breathing curve baseline, amplitude, and window of the gating session, and the breathing history of the patient is visualized with an optional range. The in‐house program features audio coaching which allows the operator via buttons to deliver breathing instructions to the patient. The program is presently not capable of auto‐gating, and in order to increase patient safety and avoid mistreatments, the screen flashes in the operator's room until the first breath‐hold is performed. The laser needs to be mounted at an inclined angle in the treatment room to assure a clear view to the measuring spot on the patient's sternum. The laser system will not yield absolute amplitude in the anterior direction; this is due to the scanning displacement of the laser when the sternum is elevated from the baseline  and can be clamped onto the side of the CT table and adjusted in the superior–inferior direction. The distance measuring laser is mounted horizontally onto a trestle and placed at the foot end of the CT table Fig. a. It poi2.A.2The mirror on the Flexarm can also be adjusted to deflect the laser 90° and give a vertical readout of the sternum position. With this setup, it can be used to find the vertical reference amplitude for the Catalyst system.2.BThe laser is attached onto a Flexarm that is connected to a universal ceiling mount which, in seconds, makes it possible for the user to easily adjust the measuring spot of the laser to a suitable region regardless of the isocenter position Fig. b. The laTo validate the laser distance measurer, we performed tests against the Catalyst system. Our first test was to establish the vertical relation between the Catalyst and laser system for horizontal surfaces; this would verify the relative factor and also check for linearity. The table top was moved upward in steps while both the Catalyst and the laser system were measuring. In Fig. , when thSeven employees were enrolled to perform a stepwise breath‐hold. The goal of the validation was to check if the two systems could be used interchangeably but with different breathing amplitudes that could be described by the ratio we found in our first test. This fixed ratio could then eventually be hard‐coded into the in‐house developed software. All test subjects used a flat WingSTEP breast board  and knee support as fixation. Due to the inclined mounting angle of the Catalyst, it is preferable to use an angled wedge under the WingSTEP breast board in order to improve the accuracy, and we also evaluated if this would improve the results for the in‐house laser system. Measurements with an inclined breast board for four test subjects were performed.An intra‐patient reproducibility test was also performed. This consisted of a test subject performing six independent DIBH sessions with stepwise breath‐holds while scanning with both the laser and Catalyst systems. This mimics the stand‐alone performance of the in‐house laser system when it is used both during CT and treatment.32 = 1.00.The table top was moved upward in steps while both systems were being measured Fig. b. The beThe reproducibility for one test subject was evaluated for the in‐house system. Figure Seven employees were enrolled to see how the chest wall angle differences affected the relative differences between the two systems. It was found that the relative difference changed between the test subjects, but was in average close to the number we found with the horizontal table. At our institute, the patients have a DIBH amplitude that is 80% of the maximum inhalation, and we also investigated the best fit factor for this degree of inhalation Table . We founLastly, the integration of a 10° wedge under the WingSTEP was tested, and the mean ratio for four test subjects changed from 1.57 ± 0.13 to 1.27 ± 0.09 between the in‐house laser and the Catalyst system. The standard deviation of the ratio corresponds to a ± 1.5 mm standard deviation for 20 mm DIBH amplitude when the wedged pillow is used. The maximum difference in best fit factor range was originally 0.15, but decreased to 0.12 with the wedged pillow.4The in‐house laser system was primarily developed as a stand‐alone DIBH system; however, it was also evaluated against the Catalyst system to see if they could be used interchangeably. We found a very good correlation between the two systems for horizontal surfaces. A fixed factor of 1.37 describes the vertical ratio between the two systems for horizontal surfaces, and it showed a linear relation. Adding a 10° wedged pillow reduced this factor to 1.14. A steeper incident angle would be beneficial to both systems. A steeper incident angle would improve the reproducibility of the in‐house system and lower the standard deviation. A wedge under the WingSTEP breast board is now standard in our clinic.We assessed the reproducibility of the laser system, and due to the fixed position of the laser in the treatment room, the reproducibility was very good over the whole DIBH range with a mean standard deviation of 1.0 mm. This reproducibility experiment mimics the performance of the system in stand‐alone mode where the measuring angle at CT is the same as in the treatment room. The laser system is currently in clinical testing as a stand‐alone system. In absolute mode, the system measures the vertical height of the sternum which will give the same amplitude as the Catalyst system, and in this mode, the laser system can be used as reference during CT for the Catalyst system.We also evaluated the performance of our laser system against the Catalyst system in relative mode. The correlation was good in the internal study with seven test subjects, but the test subjects had variations in sternum angle that led to differences in the ratio between the two systems. At the 80% maximum inhale level, a mean ratio of 1.51 was the best fit between the two systems, which is somewhat larger than the 1.37 ratio found for horizontal surfaces. A difference of 0.14 would imply that the mean sternum angle of the seven test subjects was inclined in the superior direction from the horizontal plane. When the lungs are filled with air, the xiphoid process will elevate while the cranial parts of the chest wall will remain relatively stable, and hence this will lead to a small angle on the chest wall even if the gating spot was chosen to be at a horizontal part of the sternum. This would imply that an angled wedge under the WingSTEP breast board could be a good compromise, and shift the mean ratio closer to 1.00. The test with the angled wedge under the WingSTEP shifted the mean ratio from 1.57 ± 0.13 to 1.27 ± 0.09 between the laser and the Catalyst systems, and this will improve the interchangeability of the two systems.When the same inclined angle is used both during CT and treatment, the scanning displacement of the laser system will not influence the treatment results in relative mode provided that both the positioning and breathing performance is kept similar. This is the case if the laser system is used both for reference at CT and during treatment sessions. If the Catalyst and laser system are used interchangeably with the mean patient ratio, there could be a small error in the amplitude in the range of 0–3 mm if one does not take the angle of the sternum into account. The maximum difference in ratio was 0.12 with the angled pillow, which for 20 mm amplitude translates to a 2.4 mm error. A small error would have little impact on the quality of the treatment if the patient is repositioned after portal imaging, but it will influence the amount of air inhaled and hence the cardiopulmonary dose might be different than planned. If the two systems are used interchangeably, a wedged pillow is recommended.Anzai Medical has recently released a resembling commercial solution but there is no published data in the literature to date.We present a deep inspiration breath‐hold system for planning and treating breast cancer patients. Our laser system is capable of measuring the position of the chest wall with high frequency and precision in real time. The tests we performed showed good reproducibility and the system can be used in absolute or relative mode. In absolute mode, it can be used as reference for Catalyst at CT, and in relative mode, it can be used as stand‐alone system with high reproducibility. The system is currently in clinical testing as a stand‐alone system in relative mode. The most important features of our in‐house system are its simplicity, its noninvasiveness, and its low cost for performing DIBH.


IVF) outcomes. In the present study, the potential impact of small ovarian endometriomas on the quantitative and qualitative outcomes of IVF was evaluated in the same individual.To clarify the effects of small endometriomas on in vitro fertilization (IVF or intracytoplasmic sperm injection were evaluated. Single frozen embryo transfer cycles were performed, with separate data collections for both the affected and the unaffected ovaries, which allowed for an evaluation of the implantation rate.A retrospective analysis was performed, in which 118 infertile women with unilateral endometriomas that were <40 mm in size and who underwent The mean antral follicular count and the number of follicular flushings, retrieved oocytes, and obtained embryos were significantly lower for the endometrioma‐containing ovary than for the contralateral, intact ovary. No significant difference was observed regarding the blastocyst retrieval and good‐quality blastocyst retrieval rates, pregnancy rate, and clinical pregnancy or live birth rate.Although the patients with a small endometrioma had a decreased ovarian reserve, they had lower pregnancy rates. The decision to transfer an embryo from an endometrioma‐containing ovary or from a contralateral, intact ovary also might not influence the pregnancy rate. The quantitative ovarian reserve, embryo quality, and IVF outcome of women with a small endometrioma who undergo ART but with a high average age remain a matter of debate because relevant evidence is scarce. Therefore, further studies are needed to determine whether the endometrioma plays a role in the decrease of fecundity or in the lower pregnancy rates after IVF. Thus, the objective of the present study was to evaluate the quantitative and qualitative IVF outcomes in ovaries with and without a small  endometrioma in the same individual, with a high average age of the participants.22.12. The exclusion criteria were: (1) a previous history of any systematic disease or malignancy; and (2) older than 45 years.In this retrospective analysis, 118 infertile women with a unilateral endometrioma that was <40 mm and who had undergone IVF or ICSI from April 2011 to March 2014 were examined. All the patients met the following inclusion criteria: (1) no previous history of adnexal surgery; (2) both ovaries were present; (3) a diagnosis of a unilateral endometrioma; (4) a menstrual cycle duration that ranged from 25 to 35 days; (5) no clinical sign of hyperandrogenism; and (6) a Body mass index (BMI) that ranged from 18 to 25 kg/mAn ultrasound‐based diagnosis of endometrioma was achieved following the visualization of persistent, round, homogeneous hypoechoic “tissue” with low‐level echoes within the ovary, as previously described.Written informed consent was obtained from all the patients. This study was approved by the Ethical Review Board of Toho University Medical Center Sakura Hospital, Sakura, Japan.2.2Samples of blood (5 mL) were collected on day 3 of menstruation during the IVF cycle and were centrifuged. The resultant serum samples were frozen at −80°C until subsequent assessments of the levels of anti‐Müllerian hormone (AMH), follicle‐stimulating hormone (FSH), and estradiol (E2) were performed. The serum AMH levels were measured with a commercial assay kit . The detection limit of this kit was 0.16 ng/mL.2.3The number of early antral follicles was determined by ultrasound examination on day 3 of IVF. Ultrasonographic (USG) measurements were performed with a multifrequency transvaginal probe , as previously described.The ovarian response was assessed by the total dose of gonadotropin (recombinant FSH or hMG) that was required for ovarian stimulation, the number of follicles on the day that the oocyte was obtained, the number of retrieved oocytes, and the numbers of embryos that were obtained from the endometrial ovary and the contralateral, intact ovary.“Pregnancy” was defined as a positive serum β‐hCG test and “clinical pregnancy” was defined as the ultrasonographic demonstration of an intrauterine gestational sac 4 weeks after the embryo transfer.2.4The patients’ age, BMI, duration of the menstrual cycle, and tumor size were recorded as the baseline clinical characteristics. In addition, on day 3, the serum levels of the AMH, FSH, and E2 were recorded, along with the total number of doses and the duration of recombinant FSH/hMG stimulation. The following were evaluated and compared for the endometrioma‐containing ovary and the contralateral, intact ovary: the AFC, the degree of follicular flushing (follicular size: ≥17 mm), the oocytes that were retrieved, the embryos that were obtained, the blastocyst retrieval rate, the good‐quality blastocyst retrieval rate, the pregnancy rate, the clinical pregnancy rate, and the live birth rate. The primary outcome was the clinical pregnancy rate per cycle. The ovarian response to gonadotrophin stimulation was considered as a secondary outcome.2.5U test was used if the continuous variables were not normally distributed and the Student's t test was used if the continuous variables were normally distributed. P‐values of <.05 were considered to be significant. The results were expressed as the arithmetic mean±SD, range, and median. JMP software  was used for the statistical analysis.The chi‐square test or Fisher's exact test was used to compare the categorical variables. In order to compare the means of the continuous variables, the non‐parametric Mann‐Whitney 3In total, 118 women were evaluated in this study and their clinical characteristics, as well as those of their endometriotic tumor, are summarized in Table In this study, no complication  was observed. In some cases, contamination of the follicular fluid was difficult to avoid during the retrieval of the oocytes in the endometrioma‐containing ovary. In all, seven of the 118 endometrioma‐containing ovaries were situated in a deep position relative to the surface; however, these ovaries were able to be reached and the follicles were able to be punctured in all cases.4The objective of the present study was to evaluate the quantitative and qualitative IVF outcomes of women with and without a small endometrioma. Overall, the results suggested that the presence of an ovarian small endometrioma reduces the ovarian reserve but does not significantly affect the pregnancy rate.The findings of this study were unique because the single embryo transfer policy that was followed, together with the separate data collections for both the affected and the unaffected ovaries, allowed for the evaluation of the implantation rate. The implantation rate thus could be directly attributed to the ovary with the endometrioma or to the contralateral, healthy ovary. Embryo cryopreservation is a routine part of ART that is associated with many benefits. Most studies have suggested that cryopreservation maximizes the cumulative success of each and every IVF cycle.The management of endometriomas that are <40 mm in size in women who attempt to conceive remains a matter of debate.Few studies have compared the numbers of oocytes that are produced by endometrioma‐containing ovaries and healthy ovaries in the same individual. One of the first to compare the responses of affected and unaffected ovaries to gonadotropins showed the production of a reduced number of co‐dominant follicles in endometrioma‐containing ovaries in response to ovarian stimulation and this reduction was more evident in women with endometriomas that were >20 mm in size.Laparoscopic ovarian surgery is a major topic in the field of reproductive medicine and the excision of ovarian endometriomas has been reported to be associated with detrimental effects on the ovarian reserve immediately after surgery.The precise risks that are associated with oocyte retrieval following treatment for an endometrioma are not well known. According to one study, at least five complications can be associated with a conservative approach in patients who are undergoing IVF cycles: (1) rupture of the endometrioma; (2) development of a pelvic abscess; (3) a failure to recognize an occult, early‐stage malignancy; (4) difficulties in oocyte retrieval; (5) contamination of the follicular fluid with the contents of the endometrioma; and (6) the progression of endometriosis.In this study, no significant difference was observed in the AMH levels between the pregnant and the non‐pregnant women. Although some studies have reported that AMH can be a predictor of the ovarian reserve and the success rate of IVF,Several limitations affect the results of the present study. First, this study included only a small number of participants with a relatively high average age (40.4±0.9 years). The overall pregnancy rate in this study was relatively low but could be explained by the high average age of the participants, as the overall pregnancy rate was age‐appropriate. The findings of this study were unique, in that the average age was relatively higher than that in similar studies. Other studies also were limited to patients who were younger than 40 years of age at the time of the IVF/ICSI cycle.In conclusion, despite the small number of participants in the present study, it was concluded that women with a small endometrioma and with an average age of 40 years have a reduced ovarian reserve but this does not significantly affect the pregnancy rate. A large, prospective study therefore is necessary in order to clarify the effects of small endometriomas on IVF outcomes.Conflict of interest: The authors declare no conflict of interest. Human rights: All the procedures that were followed were in accordance with the ethical standards of the responsible committees on human experimentation  and with the Helsinki Declaration of 1964 and its later amendments. Informed consent was obtained from all the patients to be included in the study. Animal rights: This article does not contain any study with animal participants that was performed by any of the authors.


To assess the effectiveness of a traditional birth attendant (TBA) referral program on increasing the number of deliveries overseen by skilled birth attendants (SBA) in rural Kenyan health facilities before and after the implementation of a free maternity care policy.In a rural region of Kenya, TBAs were recruited to educate pregnant women about the importance of delivering in healthcare facilities and were offered a stipend for every pregnant woman whom they brought to the healthcare facility. We evaluated the percentage of prenatal care (PNC) patients who delivered at the intervention site compared with the percentage of PNC patients who delivered at rural control facilities, before and after the referral program was implemented, and before and after the Kenya government implemented a policy of free maternity care. The window period of the study was from July of 2011 through September 2013, with a TBA referral intervention conducted from March to September 2013.p < 0.001). The absolute increases in SBA delivery rates from the pre-intervention period to the intervention period before the implementation of the free maternity care policy were 4.7 and 17.2 % in the control and intervention groups, respectively (p < 0.001). After the policy implementation the absolute increases from pre-intervention to post-intervention were 1.8 and 11.6 % in the control and intervention groups, respectively (p < 0.001).The absolute increases from the pre-intervention period to the TBA referral intervention period in SBA deliveries were 5.7 and 24.0 % in the control and intervention groups, respectively (The percentage of SBA deliveries at the intervention health facility significantly increased compared to control health facilities when TBAs educated women about the need to deliver with a SBA and when TBAs received a stipend for bringing women to local health facilities to deliver. Furthermore, this TBA referral program proved to be far more effective in the target region of Kenya than a policy change to provide free obstetric care. Modern obstetric care and hygienic childbirth practices have been heralded as the main reasons for the decrease in the neonatal mortality rate during the 20th century . This reMaternal and newborn mortality are frequent in Kenya where a high number of deliveries occur at home, often under the supervision of a traditional birth attendant (TBA) . A TBA iIt is interesting to note that increased training of TBAs has not been shown to reduce maternal mortality during childbirth. A systematic review by Wilson et al. found that the strategy of training and support of traditional birth attendants reduced perinatal and neonatal deaths but had no significant effect on maternal mortality . A jointAlthough TBAs are not as effective as SBAs at reducing childbirth morbidity and mortality, they continue to play an important role in women’s health. In the 1990’s, WHO, UNICEF, and UNFPA described the role of TBA programs in promoting global reproductive health as: a) enhancing the links between modern health care and communities; and b) increasing the number of births attended by trained birth attendants . The ubiAccording to the 2008–2009 Kenya Demographic and Health Survey, over 92 % of Kenyan women are seen at least once per pregnancy at an antenatal clinic, but only 44 % of deliveries are attended by SBAs. This rate has only improved by 3 % since the previous demographic study conducted in 2003. Additionally, there are regional discrepancies in care during delivery. For example, data collected in 2003 from Western Province revealed that SBAs delivered only 28 % of births. In contrast, in Central Province, the most urban of all provinces, 70 % of women delivered with a SBA . These fThe available data from 2008 show that deliveries assisted by SBAs in Eastern Province were 42.8 % . In contOn June 1, 2013 the Kenyan government abolished all fees for maternity services in public facilities with the expressed purpose of increasing SBA deliveries. The purposes of our study were to assess an expansion of the previously studied TBA referral system to a health facility in Yatta sub-county, and to further determine if the TBA referral program increased the SBA delivery rate beyond the effect of the abolishment of fees for services.We conducted a non-randomized controlled trial to investigate if women’s exposure to TBA referrals and a community education program changed their medical facility/SBA-seeking behavior for delivery. We hypothesized that enlisting the support of TBA referrals would significantly increase the number of women who choose to give birth in a health facility with a SBA present.The site of the study is in southeastern Kenya, in Yatta sub-county of Machakos County. The region is part of the arid and semi-arid lands of Kenya, populated by the Kamba tribe. Dry land rain-fed agriculture and small-scale animal husbandry are the primary source of livelihood for the non-urban population that is included in this study. Extreme poverty and geographic isolation of the population limit access to health care and contribute to a high child and neonatal mortality. The intervention facility was chosen because of its remarkably low percentage (2.4 %) of deliveries of antenatal care patients occurring in a facility with a SBA . The YatIn February 2013, we held a meeting with TBAs from the area surrounding the Kisiiki healthcare facility in Yatta sub-county to recruit them into the TBA referral program in order to expand the work of Tomedi et al. . We met The Kenya government/Ministry of Health has emphasized the importance of health facility deliveries and that TBAs are not legitimate providers of health care (e.g. they are practicing without a license). The TBAs are aware of that, but in this and other meetings have stated that pregnant women continue to come to them requesting their assistance, and they feel an obligation to help. The lead author was told in preliminary meetings with TBAs (before the study was started) that they do not charge a fee for their services, but other community sources  have said that they are paid by the client’s family, an amount that could range from KSH 200 to 500. Because of the government’s stated position regarding TBAs, they have been reluctant to refer the client when complications occur. The pregnant women, when asked about barriers to facility birth, have expressed a fear that they might deliver while traveling the long distance to a health facility. Therefore, in addition to providing the TBAs with an educational message for them to deliver to their clients, the meeting addressed other concerns and barriers. A Ministry of Health official in charge of maternity services for the district spoke of the important role of the TBAs to educate their clients and improve maternal outcomes. She and the hospital staff welcomed and encouraged the involvement of TBAs (up to the point of delivery). It was recognized that the TBAs would continue to be consulted by many families. They are asked to assess if a woman is in active labor, and if there likely is adequate time for the trip to the health facility. The TBA then accompanies the woman in case delivery should occur en route. The stipend paid to the TBA is considered a “per diem” to defray her personal expenses for the trip to the health facility. The amount of the stipend was chosen because the volunteer community health workers (CHWs) in the target area of the non-governmental organization that supports this project are paid a “per diem” of KSH 200 per day of work. The number of TBAs participating in the referral program was 38.The number of births from the Kisiiki area, which was estimated by the number of new PNC patients, was compared to the rural control facilities in the Yatta sub-county. Data from the Ministry of Public Health and Sanitation (MOPHS) facilities’ records was used to determine PNC visits and pregnant women who delivered at a rural health facility with or without a TBA.The control facilities consisted of 28 rural dispensaries and health centers within the Yatta sub-county that did not participate in the TBA referral program. The two intervention facilities for which results were reported in the previous study  were excThe pre-intervention data was collected from July 2011 through February 2013. In the control facilities, the number of new PNC patients and the number of deliveries were 2112 and 218 respectively. The intervention facility (Kisiiki) recorded 334 new PNC patients and 12 deliveries during the same time period.These pre-intervention figures were compared with post intervention data collected from March 1, 2013 through May 31, 2013  and from June 1, 2013 through September 30, 2013 (after the enactment of the policy). Therefore, the post intervention period was divided into subintervals, one before the free maternity care policy was enacted and one after the policy went into effect. These periods were analyzed separately to assess changes in SBA-attended birth rates related to the effect of the change in the government policy.The University of New Mexico Human Research Protections Office and the Kenyatta National Hospital-University of Nairobi Ethics and Research Committee in Kenya approved the study.The SBA rate was calculated as a percentage of the prenatal care (PNC) patients who delivered at the facility, with the denominator being the number of first visit prenatal care patients and the numerator being the number of deliveries at the facility. The total number of the PNC patients and deliveries at all non-intervention rural facilities were used for the control percentages. Chi-square tests were used to test differences in percent of SBA (facility) deliveries between intervention and control groups for individual time periods: baseline rates (pre-intervention), for the rates during the entire 7-month intervention period, and for the rates during the two parts of the intervention period (before and after the implementation of the free maternity care policy). Differential changes over time between the intervention and control groups were tested using binomial regression with a term for the interaction between group and time. Statistical analyses were performed using Stata version 13 .2 = 15.33; p < 0.001) (Table During the pre-intervention (baseline) period, the percent of SBA deliveries was significantly higher in the control facilities 10.3 %) than in the intervention facility (3.6 %) .During the 7-month intervention period, 16.0 % of PNC patients delivered with an SBA at the control facilities, compared to 27.6 % of PNC patients at the intervention facility Tables , Fig. 1.χ2 = 2.07; p = 0.04).Before the free maternity care policy Table , 15.0 anχ2 = 10.29; p < 0.001). The absolute increases in SBA facility deliveries between the baseline period and the period with free maternity care were 1.8 and 11.6 % in the control and intervention groups, respectively .After the free maternity care policy implementation Table , 16.8 anThe Kenya government implemented a policy that provided free maternity care halfway through our post intervention period. In order to assess the effect of this new policy on SBA deliveries, the 7-month intervention period was divided into two sub- periods Table , Fig. 2:χ2 = 0.46; p = 0.50).In the control facilities, the SBA delivery rate increased from 15 % in the first intervention period (before the free maternity care policy) to 16.8 % after the policy implementation  provides the funds, or the government takes over that responsibility. The amount of funds required is small relative to other costs of the health care system. Other NGOs and low-income developing country governments have decided to pay a salary to lay CHWs for community work, at greater cost than this TBA program. However, the hope is that over time the “norm” in the community will be a health facility delivery rather than a home delivery, and the TBA stipend will not be necessary.There are recognized limitations of this quasi-experimental study. The relatively brief time period and the number of deliveries in the target facilities limit the power and strength of the conclusions. The intervention and control sites were not randomly assigned, which increases the risk of the influence of potential confounding variables. Unmeasured factors, such as improved accessibility and cultural issues or preferences may have contributed to the results, but are not likely to have influenced the outcome significantly more in the intervention region than in the control region. We did not collect qualitative or quantitative data on the population characteristics, potential confounders, and about the community’s reasons for lack of response to the Kenya policy change. The restriction of the study population to one ethnic group in one district limits the generalizability of the results.The efforts in Kenya thus far to increase SBA deliveries has met with very limited success. Our approach of involving TBAs in a referral program could offer the potential for Kenya and other sub-Saharan African countries to improve SBA facility delivery rates at a very low cost. A larger study of this approach would seem warranted in other regions and countries where TBAs play an active role in the community.The percentage of SBA deliveries at the intervention health facility significantly increased compared to control health facilities when TBAs educated women about the need to deliver with a SBA and when TBAs received a stipend for bringing women to local health facilities to deliver. Furthermore, this TBA referral program proved to be far more effective in the target region of Kenya than a policy change to provide free obstetric care.