Finally, a series of comparative experiments indicated that the differential EFS highlighted in the present study exhibits good linearity and accuracy.Thus far, despite the development of electric field sensors (EFSs) such as field mills, optoelectronic EFSs and microelectromechanical system (MEMS)-based EFSs, no sensor can accurately measure an electric field in space due to the existence of space charge and the influence of charge attachment. To measure a spatial synthetic electric field in an ion flow field, a double potential independent differential EFS based on MEMS is proposed. Compared with other EFSs, this method has the advantages of independent potential (without grounding) and the ability to support the measurement of the synthetic ion flow electric field in space. First, to analyse the charge distribution after the sensor is involved exposed to an electric field, a simulation model was constructed. Then, given the redistribution of the spatial electric field in space and the influence of the surface charge on the sensor, the quantitative relationship between the electric field to be measured and that measured by the proposed sensor was obtained. To improve the performance of the EFS, a set of synthetic field strength sensor calibration systems that consider spatial ion flow injection was established. Furthermore, the parameter  With the industrial developments and improvement in living standards, the demand for electricity has increased, and high-voltage, direct current (HVDC) transmission lines have been widely developed worldwide because of their advantages of long transmission distance, large transport capacity and low cost. However,-the increased voltage level introduces problems related to the electromagnetic environment, such as an increase in the synthetic electric field, audible noise, radio interference, and loss of ion flow .Corona discharge occurs on the surface of an HVDC transmission line when the electric field strength exceeds the air breakdown field strength ,3. When For a stronger smart power grid, a broadband, full-time coverage, high-sensitivity sensing system is an effective strategy against emergencies in a power system, such as lightning, operating trouble, and insulation failures. Among the four parameters of ion flow, audible noise, synthetic electric field and radio interference, the synthetic electric field closely interacts with or otherwise affects the insulation of a material , the opeOver the past decades, field mills were most commonly used for measuring ionized fields because of their stability and linearity ,8. FieldRecently, smaller-sized devices based on the Pockels effect ,3, electRecently, a serious of new type EFSs have been proposed. Chu proposed a new type based on torsional resonance , and Andλ. To verify the accuracy of this measurement, we conducted a series of experiments and compared the measured results with the calculated results, which showed that the proposed sensor exhibits good linearity and high accuracy. To measure the space synthetic electric field in the ion flow, we designed a double-potential independent EFS based on MEMS technology. Compared with other EFSs, this technology has the advantages of small volume, independent potential (without grounding), and the ability to support the measurement of the synthetic electric field in space. As a first step in the present study, we designed an electrostatic comb-drive and capacitive induction EFS and analysed the measurement principles. We then constructed a multi-physical simulation model to identify the relationship between the measured value and the electric field to be measured. Based on measurements in the electrostatic field, we deduced the relationship between the output voltage and the electric field. The calibration process was subsequently analysed in detail to obtain the parameter MEMS technology is widely used in consumer electronics  for its lightweight, low-cost, low-power-consumption and easy batch production . With thAs is shown in A capacitive induction structure is used to detect the electric field . The solCompared with thermal driving, electrostatic driving has the following characteristics: the driving current is small, approaching zero; as a consequence the resistance loss is extremely small; and the structure of the EFS is sufficiently sound to not be broken by heat. A schematic of the electrostatic driving structure is shown in When a driving voltage is applied at both ends of the drive electrode, an inducted charge will be produced at both ends of the electrode. Electrostatic attraction is induced under the joint action of a positive inducted charge on the positive electrode and a negative inducted charge on the negative electrode.C is:The left electrodes are fixed by an anchor, and the right electrodes are removable. The total driving capacitance xF is:Thus, the driving force When a conductor is placed in an electric field, an inducted charge is generated on the surface of the conductor. In the present EFS, multiple capacitors act as sensing structures.sn represents the number of the sensing capacitors, sA represents the effective area of the sensing electrode, and D represents the distance between the sensing electrode and the ground.The capacitance of the sensing part is:Thus, the inducted charge is:As a result, the inducted current is:The fabrication feasibility and performance of the sensor are the main aspects that should be considered. To achieve high linearity and strong output signals, a simulation process is needed. The size of each part of the sensor can be is determined by parameter scanning analysis, as shown in 2 layer as an electrical isolation layer, is deposited on the device layer by a plasma-enhanced chemical vapour deposition (PECVD) process. Then, after etching the SiO2 layer by a reactive ion etching (RIE) process to form contact holes, an Al layer is sputtered on the holes to form pad. After that, deep reactive ion etching (DRIE) is used to etch the device layer to form the main structure of the EFS. A polyimide layer is used to protect the structure from destroyed in the subsequent process. Then, the Si substrate is etched by DRIE from the back and the buried oxide layer is etched from the back with RIE. Finally, the polyimide layer is released, forming a suspended structure.The EFS is fabricated on a silicon-on insulator (SOI) wafer with a resistivity of 0.01 Ω∙cm. First, a SiOThe MEMS EFS is a few cubic centimetre device in size. The packaging of the device is composed of a hollow metal cylinder with an insulating material on the side surfaces. If the top plane of the package is not a conductor, then the dielectric material will accumulate charge and subsequently become polarized, generating an uncertain electric field, resulting in the measurement meaningless. When considering above reasons, the material of top plate of the EFS is determined as metal.2.The lower metal plate provides a stable grounding potential for the sensor chips and signal processing circuits. The side is made of an insulating material, maintaining a stable potential difference between the top and bottom plate and thus providing a stable internal electric field. As shown in In The EFS was placed in the space below the transmission line to measure the space synthetic electric field. Additionally, the size of the EFS covers tens of cubic centimetres.t0 and the time when the surface synthetic electric field is zero is defined as t1, then a transient process current flows through the middle interface from t0 to t1.In the ion flow field, due to the principle of conservation of charge and current, charge accumulates on the middle interface because of the difference between the conductivity and the dielectric constants of the two sides. If the time at which the first charged particle reaches the metal interface is defined as J1 and J2, the following equation is used:The zero-field model was used to analyse the charge accumulation. That is, charged particles continuously reach the metal interface to neutralize the charges of opposite polarity on the metal plate until the surface synthetic electric field on the middle interface reaches zero. According to the principle of conservation of electric charge, when current densities from the two sides are The differential form of Ohm’s theorem is: Thus:The Gauss theorem is:Thus, the accumulated charge density on the middle interface is:For the top shell, the metal plate induces negative charges on the upper surface in a positive electric field, and the intensity of the induced charge is related to the electric field intensity and the outside dielectric constant:The ion charges can reach the top shell directly, and when the surface synthetic electric field on the middle interface reaches zero, the accumulated charge stops increasing.By contrast, on the bottom shell, accumulated charges are redistributed over the whole device. The principle of superposition of charge surface density was used to balance the conductor to analyse the charge on the bottom shell.In the absence of ion flow and when the uncharged device is placed into an electric field, the induced charge intensity of the top and bottom are represented by When no external electric field exists other than ion flow, the induced charge intensity of the top and bottom are the same Combining the two situations, i.e., when the device is placed in an electric field, the accumulated charge of the top shell is zero, 2. We used a scale model to simulate the real situation. The EFS is 10 cm long and 10 cm wide. The background electric field is generated by a 120 cm long and 100 cm wide rectangle. Boundary 1 was set to a high voltage of 15 kV, and boundary 2 was set to ground potential. Thus, the background electric field was 15 kV/m. According to [ρ over the entire region was set to 6 ×10−7 C/m3, except for inside the area of the sensor. The initial descent rate of the charged particles was 1 m/s. Additionally, the ion flow density was set to 100 nA/m2 based on previous experience with HVDC transmission lines [−4 to 2.42 × 10−4 m2/(V∙s) under atmospheric conditions [−4 m2/(V∙s).To determine the relationship between sensor detection and the original synthetic electric field strength, we constructed a simulation model. The sensor is encapsulated in a cube, which is a symmetrical structure. The top and bottom plate of the EFS is made of gold, and the sidewall is made of SiOrding to , the spaon lines . Ion mobnditions ; we used(1)The charge density around the sensor is set to a determined value.(2)The charged particles will move along the electric field lines in the electric field. With time, the particles accumulated on the surface of the package of the sensor will generate a reverse electric field to stop particles of the same polarity from falling on the surface. We assume the charging process completes when no additional particles reach the metal shell of the sensor.Under the following assumptions, we performed several simulations to study the influence of ion flow on the MEMS EFSs:Transmission systems with different voltage levels cause different degrees of corona discharge. Because of the difference in ambient temperature and humidity, as well as the different operating modes of the transmission system, the space charge density will differ. Directly studying the influence of the space charge density on the MEMS EFS should offer an effective solution.Charged particles in the electric field will undergo a complex movement process of collision and decomposition. The movement process is mainly influenced by the electric field force.According to Gauss’s theorem, when the initial space charge density is zero, the surface charge density at the top and bottom surfaces induced under a 15 kV/m background electric field should be:The charge induced at the top surface is negative, and the charge induced at the bottom surface is positive. During the initial steps, the positive charge at the top surface will neutralize the initial induced negative charge until the charge density is zero. The accumulation of positive charge on the top surface will generate a reverse electric field to prevent ion flow. When the charging process is completed, the charge density of the top surface will not change.The particle trajectories are shown in e is increased, the electric field component of the R-axis increases, leading to the lateral offset of the ions. This phenomenon will becomes more apparent with increasing charge density on the top surface.When charged particles are near the metal shell, a reverse electric field is generated by the positive charges on the top surface, which decreases the velocity of charged particles in the vertical direction to zero and increases the velocity of charged particles in the reverse direction. Additionally, the charged particles will move laterally due to the lateral imbalance in the electric field force generated by the positive charges on the top surface. Eventually, all charged particles will migrate around the sensor and move down, forming a charged air zone. The area of zero-charge density is called the ‘charge-empty area’.According to the previous simulation analysis, the top plate of the EFS can accumulate charged particles in the space electric field, forming a charge-empty area in the EFS adjacent area.inE comprises three components: the original space electric field E0, the electric field E1 generated by the charged particles accumulated on the top surface, and the electric field E2 formed by the formation of the empty area, which is changed by the original space charge. We thus obtain the following equation:The sensor detection The sensor is sensitive only to the electric field in the vertical direction. Thus, the electric field in the other direction is not considered in this research. E0 at different distances between the sensor chip and the top surface with the same boundary conditions described in part C of this section. We measured the electric field inE of the chamber in the simulation described in part C of this section. Finally, we used the same measurement method to measure the electric field E1 in the case of accumulating charge on the surface of the package. The results are shown in We measured the value of each component by simulation to find the relationship among the components. First, we used parallel plates to generate an electrostatic field to simulate the electrostatic field generated by high-voltage transmission lines. In addition, the uniformly distributed space charges simulate ion flow near the transmission line. We measured E0 plus E1 is approximately equal to inE. Thus, we ignored the component of E2. With further research, we found that E1 is proportional to the distance between the chip and the top surface. According to this relationship between E1 and the distance between the chip and top surface, we designed a differential EFS. The concrete structure is shown in E1 is proportional to the distance between the chip and top surface, E21 = λE11, and λ is related to the location of the two chips.As shown in From the following three equations:We obtained:λ is been determined, E0 can be obtained from Ein1 and Ein1:After E1, ensuring the accuracy of the measurement. Because of these characteristics, the sensor can measure the space synthetic electric field in an ion flow field.As charge accumulates on the surface of the package, introducing charge into the earth is not necessary, thereby enabling potential independence. Using the upper shell of a package to accumulate the space charge, we measured the electric field in the ion flow. The difference structure was used to eliminate the influence of the large component The ultimate goal of the present EFS is to measure the space synthesis electric field under HVDC transmission lines. First, we measured the zero drift of the EFS under zero field. Then, the relation coefficient between the output voltage of the EFS and the electric field to be measured is determined according to the output voltage of the EFS in a static electric field. After that, the calibration of the EFS in the ion flow field was thus completed. Finally, the EFS can be used to measure the synthetic electric field in an ion flow.λ, we designed the measurement system shown in To verify the function of the EFS and calibrate the coefficient of Va controls the intensity of the corona ion flow into the bottom parallel-plate electric field. The fourth layer is the upper plate of the parallel-plate electrode structure with a diameter of 0.142 mm and a length of two lines of 1.6 cm; it also serves as the second layer of the filter network. The fifth level is the lower plate of the parallel-plate electrode structure, which is a thick stainless steel ground plate. A hollow disc is positioned near the centre of the fifth level, which is used for the placement of the field strength tester. The uniform electric field in the ion flow field between the upper plate and the lower plate is key to this experimental device.The parallel-plate ion flow generator is composed of five flat plate layers with a diameter of 1 m on four insulated plastic columns. The circumjacent upward bending of the disc is designed to enable the generation of a uniform electric field around the disc and prevent discharge of the surrounding plates. The second layer is a Constantan wire net with a diameter of 0.3 mm and a length of two lines of 5 cm, which can produce a uniform ion flow. The third level is the control panel, which is made of a 0.8 cm × 0.8 cm stainless steel plate and acts as the first layer of the filter network. This layer enables a uniform distribution of corona ion flow. The voltage As shown in Vt and the parallel plates in Vt. The measurement results are shown in We first tested and verified the function of the EFS in an electrostatic field, which required determining the zero drift of the EFS in the zero field and identifying the coefficient between the output voltage and the electric field. In this section, we utilized a DC voltage As shown in E0, eliminating the interference of E1, which is the relatively larger contributor to the electric field distortion. The parameter λ is related only to the relative height of the two chips in the encapsulation structure and is independent of the applied electric field. Thus, this parameter can be calibrated according to Equation (16) after the package structure has been determined. The principle of calibration of the EFS in an ion flow field is described in great detail in the following paragraphs.Consistent with the aforementioned discussion, the measurement results of the MEMS sensor chip in the package include three parts. The use of a double cylindrical composite potential independent package structure enabled indirect measurement of the original electric field strength dE to be zero [J = pkE, where p is the space charge density and J should be a constant along z due to the continuity of current, if dE = 0, J at anywhere in the measurement region would be 0 [Due to the distortion of the electric field, demarcating and calibrating the EFS is difficult, and measurements without demarcation and calibration processes are meaningless. A small part of the EFS is calibrated in an electric field . Althoug be zero . Becauseuld be 0 . In the The space is filled with ions due to corona discharge. The function of the electric field at each point should satisfy the Poisson equation :(18)∇⋅E→J can be described as J = kpE, where k is the ion flow mobility, p is the density of space charges and E is the synthetic electric field. According to the Poisson equation and the relationship between J and k, s, p and E, we obtained the following equation [The ions formed by corona discharge move with the electric power line under the action of the electric field, thus forming an ion current. The ion current density equation : (19)E(zEn is the electric field on plane of the fifth layer. By integrating Equation (19), we obtain the voltage equation:TV is the voltage applied to the fourth layer plate. Equation (20) satisfies V(0) = 0 because the fifth layer plate is grounded. Thus, we obtain:The fifth layer is the zero point of the Z-axis, and the direction is vertical. By solving Equation (21), we obtain the mobility of the ion flow:k is included in Equation (22), and the intensity of the electric field in the air can be obtained:The ionic current mobility VT is known. The current density J can be measured by the microcurrent meter. Furthermore, the ground electric field nE can be measured by the field mill. Because the parameters of VT, J and nE can be obtained, according to Equation (23), the air synthetic electric field in space induced by ion flow can be calculated. The parameter λ can then be obtained by Equation (16). Finally, the EFS can be used to measure the unknown space synthetic electric field in ion flow field according to Equation (17).The fourth layer plate voltage Vc to 2.5 kV and adjusted the voltage Va. To realize the measurement of the synthetic electric field of ion flow field, the sensor demarcation is needed. The demarcation results is shown in λ is displayed in the following table.The encapsulation sidewall shell used in this calibration is made of Teflon material. The height of chip1 is 0.6 cm from the top of the shell, and the height of chip 2 is 2.3 cm from the top of the sensor. The distance between the second level and third level is 1 dm. We set the voltage λ = 1.861. According to Equation (17), because parameter λ has been determined, the unknown synthetic electric field in space or on ground and in an electrostatic field or in an ion flow field can be measured using the differential EFS we designed.Substituting the data shown in Es was obtained by a field mill according to Equation (22). The performance of the sensor was evaluated by comparing the measured values of E0 and the calculated values of Es. A comparison of the results is given in To verify the performance of the double differential EFS, we conducted a series of calibration experiments. Under the same experimental conditions, the double differential EFS measured the synthetic electric field induced by ion flow, which was generated and adjusted via the intensity of the ionic current and the electrostatic field. Additionally, the theoretical value of λ, the measured values of the ion-current-space electric field under different conditions were obtained. As shown in Through this demarcated value of To measure the space synthetic electric field in an ion flow field, we designed a double potential independent EFS based on MEMS technology. Compared with other EFSs, the present sensor has the advantages of small volume, independent potential (without grounding), and the ability to support the measurement synthetic electric fields in space.E0, the additional electric field E1 caused by ion flow in the area, and the electric field distortion E2. Because the component E2 is small compared with the other two fields, we ignored the influence of E2. To eliminate the effect of E1, we designed a differential potential independent structure.We first designed an electrostatic comb-driving and single-layer sidewall induction EFS. The theory of the driving and the induction components were analysed. We then designed the package of our sensor. The upper and lower plates were made of metal, and the sidewalls were made of an insulating material. When the EFS was placed in an ion flow field, the upper plate accumulated charged articles, distorting the original electric field. Through a multi-physical field simulation, we found a ‘charge-empty area’, and analysed the measurements, which consisted of three components: the original field To better characterize the performance of the EFS, a parallel-plate ion flow generator was designed, analysed, fabricated and then used to generate an ion flow for the EFS measurements. Due to the distortion of the electric field, demarcating and calibrating the EFS was difficult. A calibration method for an ion flow electric field in space was proposed based on the ion flow generator.In the ion flow field demarcation experiments, the measured value of


Ciliated hepatic foregut cyst (CHFC) is a rare benign cyst of the liver derived from an embryonic remnant of foregut epithelium. CHFC is typically asymptomatic and is found incidentally. Recent reports of malignant transformation may warrant surgical removal of CHFC. We present the case of a 54-year-old male who was discovered to have a CHFC while undergoing kidney transplant evaluation. Ciliated hepatic foregut cyst (CHFC) is a rare benign cyst of the liver derived from an embryonic remnant of foregut epithelium . PatientA 54-year-old male with end stage renal disease undergoing kidney transplant evaluation presented to hepatology clinic for further evaluation of a hepatic cyst. The cyst was incidentally found on abdominal CT, and the patient was completely asymptomatic. A noncontrast abdominal CT scan revealed a 2.3 cm lesion of low attenuation in segment IVa of the liver. Additional workup including, bilirubin, ALT, AST, GGT, hepatitis B, C, and HIV screening were unremarkable. A subsequent contrast enhanced abdominal magnetic resonance imaging (MRI) scan confirmed a 2.8 cm hypodense cyst with a 1.7 cm solid component in the posterior aspect of the cyst with enhancement. A follow-up contrast enhanced MRI was performed, which demonstrated persistent of solid component .Considering the persistent 1.7 cm solid component in the cyst, concern of hepatic cystic neoplasm was entertained. Additionally, immunosuppression after kidney transplant may facilitate progression of a neoplastic process if left untreated. Therefore, the decision was made to proceed with surgical resection. A laparoscopic approach was initially performed, which revealed a superficial hepatic cyst within segment IV of the liver, consistent with prior imaging. Given the location of the cyst, it was decided to convert to an open surgical approach. A tan, thin-walled, mucin-filled cyst (2.7 × 2.0 × 1.1 cm) was removed via cyst enucleation without complication . The patCHFC is a rare benign hepatic cyst originally described by Wheeler and Edmonson as a cystic remnant of foregut epithelium similar to bronchogenic and esophageal cysts . A literRadiographic imaging is usually insufficient for diagnosis given the variability in appearance. Typically, CHFCs are small (<4 cm), subcapsular, unilocular, and fluid-filled, but may present with findings suggestive of solid debris as seen in the above patient , 10, 11.Definitive diagnosis is made through histology which reveals a pseudostratified columnar epithelium, subepithelial connective tissue layer, smooth muscle layer, and outer fibrous capsule . PresencAlthough CHFCs were originally believed to be benign, more recent reports of CHFCs undergoing malignant transformation have challenged that dogma , 16. RatCHFC is a rare cyst, but has been more frequently diagnosed in recent years. Given the potential for malignant transformation, it is an important diagnosis to consider in the setting of a hepatic cyst. Due to the limited number of cases, further characterization and understanding of the disease is important.


Cyst infection is a common and serious complication of autosomal dominant polycystic kidney disease (ADPKD) that is often refractory. Carbapenems are frequently needed to treat to patients with refractory cyst infection, but little is known about the penetration of newer water-soluble carbapenems into cysts. This study investigated the penetration of meropenem (MEPM) into infected cysts in patients with ADPKD.Between August 2013 and January 2014, 10 ADPKD patients (14 infected cysts) receiving MEPM at Toranomon Hospital underwent drainage of infected cysts and definite cyst infection was confirmed through detection of neutrophils by cyst fluid analysis. The serum concentration of MEPM was measured just after intravenous administration and was compared with that in fluid aspirated from infected cysts.n = 12) or kidney cysts (n = 2) was 3.03 ± 2.6 μg/mL (range: 0 to 7.3 μg/mL). In addition, the mean cyst fluid/serum MEPM concentration ratio was 9.46 ± 7.19% (range: 0 to 18.8%). There was no relationship between the cyst fluid concentration of MEPM and the time until drainage after MEPM administration or between the cyst fluid/serum MEPM concentration ratio and the time until drainage.In the patients undergoing cyst drainage, the mean serum MEPM concentration was 35.2 ± 12.2 μg/mL  as “Penetration of meropenem into cysts in patients with autosomal dominant polycystic kidney disease (ADPKD)”, UMIN ID The online version of this article (10.1186/s12882-018-1067-2) contains supplementary material, which is available to authorized users. Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited kidney disease and is the fourth leading cause of end-stage renal disease (ESRD) among adults worldwide , 2. CystThis prospective observational study was reviewed and approved by the ethics committee of Toranomon Hospital in July 2013. This study was registered with the University Hospital Medical Information Network (UMIN) as “Penetration of meropenem into cysts in patients with autosomal dominant polycystic kidney disease (ADPKD)”, UMIN ID 000011292.We enrolled patients in the study according to the following criteria. All ADPKD patients receiving MEPM for cyst infection who underwent drainage of infected cysts at Toranomon Hospital from August 2013 to January 2014 were screened and patients without confirmation of definite cyst infection by detection of neutrophils in cyst fluid were excluded. We adopted the criteria for definite cyst infection of Sallee et al. (neutrophils in cyst fluid) [The symptoms of cyst infection were assessed from the clinical records, as were the laboratory findings using data obtained from the earliest tests performed after the onset of symptoms. The maximum body temperature (BT), the presence or absence of abdominal pain/back pain or tenderness and pyuria/haematuria, and the maximum white blood cell (WBC) count and serum C-reactive protein (CRP) level within one week after the onset of infection were recorded. The maximum BT, WBC count, and blood culture results were investigated before initiation of antibiotic therapy. These clinical data are presented in Table Abdominal MRI was performed in all patients with suspected cyst infection in this study because none of them had contraindications to MRI such as a cardiac pacemaker. Abdominal computed tomography (CT) was performed in the patients with suspected cyst haemorrhage. When MRI was done, transverse and sagittal T1-weighted images (T1WI), T2-weighted images (T2WI), and diffusion–weighted images (DWI) were usually obtained, as reported previously . None ofOur hospital policy was to only employ carbapenems in patients with cyst infection that was refractory to other antibiotics or patients with specific risk factors such as leukopenia, and physicians required submit reports to the infection control committee of Toranomon Hospital for using carbapenems. In all of the enrolled patients, the cyst infection had shown resistance to other antibiotics and treatment with MEPM was required. For administration, MEPM (0.5 g) was dissolved in 50 mL of saline and infused intravenously over 30 min. In each patient, we adjusted the MEPM dosage for renal function based on the Sanford Guide to Antimicrobial Therapy 2013). All patients on dialysis received the same dose of MEPM (0.5 g once a day) and the dose was not adjusted for body weight. The information about the antibiotics administered before MEPM and the duration of prior therapy, as well as the duration of MEPM administration in each patient are presented in the Additional file 013. All Percutaneous aspiration of an infected cyst was usually considered if a patient’s fever persisted for 1–2 weeks despite appropriate antimicrobial therapy as it is generally recommended . Cyst drIdentification of the isolates was performed using the MicroScan WalkAway 96 SI .In all patients, a blood sample was collected just after completion of intravenous administration to measure the serum MEPM concentration. Most of the patients were on dialysis and had an arteriovenous fistula. Therefore, blood was collected from the wrist and antibiotics were administered into an antecubital vein of the same arm. The interval between MEPM administration and cyst puncture varied among the patients and the intracystic contents were sampled when a drain was placed into the infected cyst. Blood samples or cyst fluid samples were mixed with the same amount of 3-N-morpholino propane sulfonic acid buffer just after collection. The mixed samples were centrifuged for 10 min at 3000 rpm and then stored frozen at -80 °C. These samples were sent to the Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts  in the frozen state, and all 300 μl of serum or cyst fluid was injected into an ultrafiltration device  just after thawing. The MEPM concentration in plasma or cyst fluid was determined by injecting 30 μL of the filtrate obtained by centrifugation of the ultrafiltered sample at 3000 rpm for 5 min into a high-performance liquid chromatography (HPLC) system, which consisted of a liquid transport unit  and a spectrophotometer . The mobile phase was a mixture of PIC-A reagent/methanol (75:25), the flow rate was 1.0 mL/min, detection wavelength was 300 nm, and column was HYPERSIL ODS-5 . For the assay using this system, the retention time of meropenem was 12.5 min, and lower limit of detection was 0.1 μg/mL. The intra-day and inter-day variation of MEPM measurement by this assay within 5% [The MEPM concentration ratio between cyst fluid and serum was calculated as follows: cyst fluid MEPM concentration (μg/mL) / serum MEPM concentration (μg/mL) × 100 (%).Results are expressed as the mean ± SD for data analyzed by parametric tests and as the median with interquartile range for data analyzed by non-parametric tests. A probability (P) value of less than 0.05 was defined as indicating significance. Univariate regression analysis was performed to analyze the relationship between the cyst fluid MEPM concentration and serum MEPM concentration (MEPM concentration ratio), as well as that between the cyst fluid MEPM concentration and the time until drainage after MEPM administration, and that between the MEPM concentration ratio and the time until drainage after MEPM administration.All statistical analyses were performed with the JMP® 13.0 statistical software package .Ten patients with 14 infected cysts were enrolled in this study (Table n = 12) or kidney cysts (n = 2) was 3.0 ± 2.6 μg/mL (range: 0 to 7.3 μg/mL). In addition, the mean MEPM concentration ratio was 9.46 ± 7.19% (range: 0 to 18.8%). There was no significant relationship between the cyst fluid MEPM concentration and the serum MEPM concentration  and Klebsiella pneumonia  was only 0.03 μg/mL according to a survey performed in Japan [90 of MEPM is high for some bacteria, e.g., 16 μg/mL for Pseudomonas aeruginosa. The intracystic MEPM concentration might not reach the effective level for such bacteria, which could explain why MEPM is not always effective for cyst infection. If cyst infection does not respond to antibiotic therapy with MEPM, we should consider that the intracystic MEPM concentration may be too low for it to be effective against the causative bacteria and we should also remember that Enterococcus spp. is frequent in patients with refractory cyst infection [It is often difficult to identify infected cysts in patients with ADPKD . Therefoin Japan . Howevernfection .The cyst fluid/serum MEPM concentration ratio varied among the patients, but we could not identify any factors that influenced this ratio because of the small number of subjects enrolled in this study. Neither the cyst fluid MEPM concentration nor the MEPM concentration ratio was correlated with the time until cyst drainage after administration of MEPM, suggesting that the intracystic MEPM concentration might be maintained for a considerable period. Nine of the 10 patients enrolled in this study were on hemodialysis. In these patients, the serum MEPM concentration might have been maintained at a higher level because of decreased urinary excretion –13, whicAmong the limitations of this study, the sample size was small and all of the patients were Japanese. In addition, 9 of the 10 patients were on dialysis and 8 patients had liver cyst infection. Therefore, our findings may not be generalizable to non-dialysis patients or patients with renal cyst infection. Furthermore, we only measured the serum and cyst fluid MEPM concentrations at one point in each patient, so we do not have information about the systemic MEPM concentration profile or its concentration in other cysts. We did not measure the serum of concentration MEPM at the time of cyst drainage, which might have led to underestimation of the MEPM concentration ratio (cyst content / serum). Further investigation will be needed to clarify the penetration of MEPM into infected cysts in patients with ADPKD.90 of MEPM for typical gram negative bacteria (E-coli and Klebsiella pneumonia).The findings of this study suggested that MEPM showed poor penetration into infected cysts in ADPKD patients. However, the cyst fluid MEPM concentration was higher than MICAdditional file 1:Past medical history of each patient. (DOC 48 kb)Additional file 2:Antibiotics used in each patient. (DOC 50 kb)


This paper presents a novel tangential electric-field sensor with an embedded integrated balun for sensing up a tangential electric field over a circuit surface in the near-field measurements covering the GPS band. The integrated balun is embedded into the sensor to transform the differential voltage induced by the electric dipole into the single output voltage. The measurement system with a high mechanical resolution for the characterizations and tests of the sensor is detailed in this paper. The frequency response of the sensor characterized by a microstrip line from 1.35 GHz to 1.85 GHz (covering the GPS band) is rather flat. The rejection to the magnetic field of the sensor is up to 20.1 dB. The applications and validations of the sensor are conducted through passive/active circuit measurements. Most modern consumer electronics are more portable and more multifunctional. The electronic modules are distributed compactly in a specific room to achieve more portable and more reduced-sized consumer electronics. Unfortunately, compact distributions of electric modules increase the possibilities of electromagnetic compatibility (EMC) issues of consumer electronics. EMC issues must be taken into consideration before or in the design stage in order to ensure the operational robustness and reliability of consumer electronics .The designs of EMC are increasingly challenging for engineers who want to make the field distribution over a circuit surface visible and find out which point or area is more strongly radiated. The accurate circuital and electromagnetic models have been established to evaluate these direct conducted and radiated emissions . Near-fiIn this paper, a tangential electric-field sensor covering the GPS band for EMC applications is proposed, fabricated, calibrated and validated through the measurements of passive and active circuits. The voltage induced by the sensing part of the sensor is in the differential mode. Thus, an integrated balun based on the power divider and phase shifter is designed to transform the differential-mode voltage to the single-end voltage. The measurement system is also presented. The performances of the sensor, such as the selectivity, sensitivity and rejection to the magnetic field, are investigated. The abilities to capture the tangential electric field of the sensor are validated through an HFSS simulation , as well as measurements of the passive and active circuits.This paper is structured as follows. The sensing part of the tangential electric-field sensor is an electrically small electric dipole. The reception mechanism of a small electric dipole shown in a for picquations ,33.(1)VAs presented in From a previous study , the equr = 3.66) and two layers of 0.19 mm thick Rogers4450F (εr = 3.58), is 1.142 mm. The sensor for sensing the tangential electric field is proposed based on the PCB process. In order to improve the measurement efficiency and save test time, a measurement system is developed. The block diagram of the measurement system is presented in According to the configuration of the measurement system in V means the output voltage of the sensor at the receiver port, and E means the electric-field strength at the test point. The calibration constant of the sensor relates the electric field and the output voltage at the test point. The calibration constant of the sensor is defined as the ratio of the measured electric field to the sensor’s output voltage, which is calculated using the following equation.−1 at 1.575 GHz, the resulting noise equivalent field strength is 63 dBμV/m (83 dBm−1 + (−20 dBμV)), which is regarded as the minimum detectable field strength by the proposed sensor at this frequency. Therefore, the sensitivity of the sensor under the condition of a 100-Hz RBW and −20-dBμV noise floor is 43 dBμV/m/The minimum detectable electric field is characterized in terms of the sensitivity of the sensor . The senSelectivity is also an important characteristic for an electromagnetic sensor, which is often used to characterize antennas and filters. As presented in x = 0), while the minimum value is at x = 0 where the field strength is nearly zero.In order to validate the ability to sense the tangential electric-field component, the microstrip line shown in The simulated Ex field is perfectly symmetric, and the two maximum values have the same magnitude. Additionally, the phase difference between the two maximum values equals 180 degrees. However, the measured Ex field is slightly asymmetric in terms of magnitude. The right maximum value is slightly larger than the left one. The slight difference between the simulation and the measurement is analyzed in . In thisThe feature selective validation (FSV) method is also introduced in this paper to evaluate the simulated Ex and the measured Ex. The FSV method can quantitatively estimate the comparison of data sets and translate the corresponding compared numerical values to six types of language descriptions , giving engineers visual perceptions and more details ,45. The x-axis to sense the Ex component. The scanning interval along the x axis and y axis is 1 mm. The scanned data is a big matrix stored in the measurement system. Before the measurements, the simulation works of the field distributions of the microstrip line operating on the three working states are implemented in the full-wave software. The simulated results are shown in Tangential field mappings over the passive microstrip line, operating in three states, are performed to further validate the performance of the proposed tangential electric-field sensor. For the matched microstrip line, the travelling wave propagates along the trace due to the good impedance match. The magnitudes of the sensed tangential electric field should be equal at different positions along the trace. For the open and short microstrip line, the standing wave exists along the trace. The maximum and minimum fields are distributed periodically along the trace. The minimum field, for the short state, dwells where the maximum field exists for the open state. The passive microstrip line is driven by a signal generator (Keysight N5181A) at 1.575 GHz with a power of 0 dBm. The tangential electric-field sensor is placed on the plane 2 mm above the trace, and the orientation of the electric dipole arm of the tangential electric-field sensor is in the x-axis, from 2 mm up to 12 mm, which indicates that the coupling between the adjacent traces decreases, i.e., the coupling between trace 8 and trace 7 is much smaller than that between trace 1 and trace 2.The meander line is a common type of transmission line that is widely used in a high-speed circuit design to adjust the transmission delay of some key signals. The tangential electric field generated by the meander line is investigated by the proposed tangential electric-field sensor. The experimental results of the Ex-field distribution for the microstrip line in x-axis to pick up Ex. The Ex fields generated by the meander line are mainly contributed by trace 1, trace 2, trace 3, trace 4, trace 5, trace 6, trace 7, and trace 8. From the previous analysis, each trace has a corresponding “zero-field” position along the x-axis. Therefore, a small scanning interval along the x-axis (0.5 mm) is adopted to detect these “zero-field” positions. A coarse scanning interval along the y-axis is set at 1 mm to reduce the dimensions of the scanned data. The mapping of the tangential electric-field  distributions is also conducted to have an insight into the visual tangential electric-field distribution of the meander line. The orientation of the electric dipole arm of the tangential electric-field sensor is parallel to the x-axis and y-axis is 0.5 mm. The sensor is cascaded with amplifiers to improve the sensitivity. The measured field distributions are shown in An important application of the electromagnetic sensor is to track the coupling trace and to locate the position of the noise source. In this paper, a scanning measurement on a Global Positioning System (GPS) module is conducted. The tangential electric-field sensor is placed as close as possible to the GPS module to enhance the coupling. The scanning interval along the In this paper, a tangential electric-field sensor based on a four-layer PCB, embedded with an integrated balun, is designed, manufactured and validated through measurements of passive and active circuits. The electric dipole is the sensed part of the designed sensor for sensing the tangential electric field. The sensed differential-mode voltage is transformed into a common-mode voltage using an integrated balun based on a power diver and phase shifter. Some measurements are conducted to validate the ability of the sensor to pick up the tangential electric field. The performances of the proposed tangential electric-field sensor are also investigated in this paper, such as the sensitivity in terms of the noise equivalent field strength, the selectivity for the tangential electric field and the rejections to other unwanted components.The applications of the tangential electric-field sensor are presented. First, a microstrip line is measured to validate the accuracy of the sensor when it is used to sense the tangential electric field; the measured results at 1.575 GHz show that the relative error characterizing measurement accuracy is under 10% when the proposed sensor is used to measure the absolute value of the tangential electric field; An FSV analysis technique is also introduced to evaluate the reliability of the measured tangential electric field. Second, the tangential electric fields of the meander line are measured with increasing gaps; the experimental results show that only two adjacent traces with a gap of more than 4 mm are effectively distinguished by the proposed sensor; Finally, the radiations of a real-world GPS module are measured by the sensor. The development of a wideband balun is important for designing a tangential electric-field sensor with a wider bandwidth. Our future work will involve research on the design of a more wideband tangential electric-field sensor.


Although global birth registration coverage has improved from 58% to 71% among children under five globally, inequities in birth registration coverage by wealth, urban/rural location, maternal education and access to a health facility persist. Few studies examine whether inequities in birth registration in low-income and middle-income countries have changed over time.We combined information on caregiver reported birth registration of 1.6 million children in 173 publicly available, nationally representative Demographic Health Surveys and Multiple Indicator Cluster Surveys across 67 low-income and middle-income countries between 1999 and 2016. For each survey, we calculated point estimates and 95% CIs for the percentage of children under 5 years without birth registration on average and stratified by sex, urban/rural location and wealth. For each sociodemographic variable, we estimated absolute measures of inequality. We then examined changes in non-registration and inequities between surveys, and annually.14 out of 67 countries had achieved complete birth registration. Among the remaining 53 countries, 39 countries successfully decreased the percentage of children without birth registration. However, this reduction occurred alongside statistically significant increases in wealth inequities in 9 countries and statistically significant decreases in 10 countries. At the most recent survey, the percentage of children without birth registration was greater than 50% in 16 out of 67 countries.Although birth registration improved on average, progress in reducing wealth inequities has been limited. Findings highlight the importance of monitoring changes in inequities to improve birth registration, to monitor Sustainable Development Goal 16.9 and to strengthen Civil Registration and Vital Statistics systems. Globally, birth registration coverage has improved from 58% to 71% among children under five; however, an estimated 230 million children do not have identification documents.Prior studies have established that there are inequities in birth registration coverage by several sociodemographic factors including wealth, urban/rural location, maternal education and access to a health facility.Complete birth registration is target 16.9 of the Sustainable Development Goals (SDGs) and crucial to ensuring that Civil Registration and Vital Statistics systems can provide accurate, timely and reliable information about infant mortality and other health outcomes, and monitor inequities.Out of 67 low-income and middle-income countries, 14 countries had almost complete birth registration. On average, 39 countries reduced the percentage of children without birth registration, and in 14 countries the percentage of children without birth registration increased.The reductions in average non-registration were not met with corresponding reductions in wealth and urban/rural inequities.There were statistically significant reductions in both non-registration and wealth inequities in 10 countries.There are large wealth and urban/rural inequities in birth registration which persisted while average coverage improved.Children in wealthier households and urban areas benefitted from on average improvements in birth registration.Monitoring the reduction of wealth and urban/rural inequities should be central to monitoring progress on SDG 16.9 on universal access to birth registration and legal identity.Achieving ‘legal identity for all, including birth registration, by 2030’ is goal 16.9 of the Sustainable Development Goals (SDGs).Compounding this problem of under-registration is a status quo where, although UNICEF estimates of birth registration in the past decade indicate a global increase from 58% to 65%,the continuous, permanent, compulsory and universal recording of the occurrence and characteristics of vital events’.The importance of birth registration—and eliminating inequities in birth registration—is profound. The United Nations defines civil registration as ‘In addition to the ways in which population-level inequities in birth registration can hinder efforts to measure and monitor population health, children without birth registration can face a range of exclusions and vulnerabilities. Without proof of legal identity, children are often invisible in the eyes of the state,Accordingly, given the lack of data on trends in inequities in birth registration and the importance of birth registration, this study examines the direction and magnitude of changes in on-average birth registration and wealth, urban/rural and gender-based inequalities between 1999 and 2016 in all LMICs with Demographic Health Surveys (DHS)/Multiple Indicator Cluster Surveys (MICS) data to ask whether national-level improvements in birth registration were concurrent with reductions in inequities.We combined publicly available, nationally representative DHS and MICS from 67 countries between 1999 and 2016. Both DHS and MICS use multistage cluster sampling, are designed to produce nationally representative estimates of health outcomes at the national, urban–rural and regional levelsBirth registration questions were included in the DHS from 1999 and in the MICS from 2000. For birth registration, all children under 5 years of age residing in fixed households were sampled—irrespective of whether their biological mother is also resident in the household—and interviews were conducted with the caregiver. Children who had died, were living on the street or in state institutions are not included in these surveys and we therefore expect to underestimate both the average percentage of children under five without birth registration as well as inequalities in registration.Because of our interest in changes in both birth registration coverage and inequalities, only countries with two or more surveys with data on birth registration were included in the analysis. Surveys had to include relevant covariates  and be designed to produce nationally representative estimates that could be compared over time: surveys were excluded if birth registration questions were posed differently across years or if national boundaries changed.We used publicly available data from the World Bank to create a list of regions and income-groups by country.The primary outcome was the percentage of children under five (0–59 months) without birth registration  as reported by the caregiver. This is the inverse of the MICS and DHS definition of birth registration and described children who did not have a birth certificate, whose births were not registered with the ‘civil authorities’ or whose caregivers did not know whether the child’s birth had been registered. The denominator was the number of children under five included in the nationally representative survey sample. We defined complete birth registration as non-registration less than or equal to 5%, indicating that most children in the country had their births registered.The DHS questions on birth registration were consistent over survey rounds. However, changes were made to the calculation of birth registration across MICS rounds: to allow for comparability, we recalculated birth registration estimates from MICS2 and MICS3 according to the indicator definition in MICS4, and the estimates presented here may differ from estimates included in the MICS2 and MICS3 national reports. 10.1136/bmjgh-2019-001926.supp1Supplementary dataWe included three sociodemographic covariates for disaggregation and estimating inequalities. The groups we hypothesised to be the ‘best off’ and have the lowest percentage of children under five without birth registration were selected as the reference category for analysis. Covariates included: sex of the child (boys (referent (ref)), girls), residential location (urban (ref), rural) and wealth which was used in the analysis both as an ordinal variable (quintiles from poorest to richest (ref)) and as a binary variable ). Consistent with the DHS and MICS methodology, wealth quintiles were calculated by the survey programme based on a household asset index constructed using principal components analysis where wealth quintile 1, for example, represented the poorest 20% of the households.For each survey, we calculated point estimates and 95% CIs for the percentage of children under five without birth registration on average and stratified by sex, residential location and wealth. We estimated the absolute difference in non-registration coverage among girls compared with boys and among children living in rural compared with urban areas. To estimate wealth inequalities, we calculated the slope index of inequality (SII), which accounts for the distribution of individual children across household wealth quintiles.All analyses were country-specific and we estimated change in non-registration on average and stratified by covariates. For the primary analyses, we calculated the difference in non-registration between the first available and most recent survey in each country and divided this by the number of years between surveys to estimate annual change. In addition, we estimated change by survey wave. We considered countries which maintained non-registration coverage below 5% between the first and most recent survey to have achieved complete registration.To examine changes in inequalities in non-registration over time, we estimated the absolute change in gender, urban/rural and wealth inequalities between the first and last survey, annually and between survey waves. Differences in estimates of inequality were deemed significant if the CIs between the first and most recent survey were not overlapping.All estimates were weighted to account for the multistage sampling design. Analyses were conducted in Stata 15.The final sample comprised of 67 countries and 173 nationally representative surveys which included 1.6 million children under five. Urban/rural inequalities were not insubstantial: 105 out of 173 surveys had significant urban/rural inequalities. Non-registration was 20 percentage points or higher in rural areas compared with urban areas in 45 surveys. Niger in 2006 and 2010 was the only country with an absolute difference larger than 40 percentage points between urban and rural areas. In contrast, the percentage of children without birth registration was statistically significantly higher in urban areas compared with rural areas in six surveys. Gender inequalities in registration were observed in fewer surveys and were smaller in magnitude. In 17 surveys, the absolute difference in non-registration was statistically significantly higher among girls compared with boys, however the largest inequality was 3.9 percentage points in Mali in 2006. In five surveys, the reverse was observed, and non-registration was significantly higher among boys—the largest gap was 5.3 percentage points in Swaziland in 2014.Annual decreases in non-registration ranged from 5.7 percentage points in Mozambique to 0.001 percentage points in Honduras. A total of 26 countries achieved an annual decrease greater than 1 percentage point, and 8 of these countries achieved decreases greater than 3 percentage points. Annual increases in non-registration were smaller compared with decreases and ranged from 0.2 percentage point in Haiti to 3 percentage points in Zimbabwe. Annual increases in non-registration greater than 1 percentage point were observed in four countries. The flowcharts in To our knowledge, this is the largest global study on birth registration, which combines data from 9.3 million children in 173 nationally representative DHS and MICS surveys across 67 LMICs countries to examine changes in averages and inequalities in birth registration during the Millenium Development Goal (MDG) and SDG period in a comparative and systematic way. We contend that the wealth and urban/rural inequalities in registration our findings reveal are unfair, unjust and avoidable and therefore represent inequities.There are a number of limitations to this study. Although we rely on the most recent data available, the most recent surveys in our sample are from 2015 and may not reflect the most current coverage of birth registration. Notably, we do not examine access to birth certificates—documentary proof of registration—which, prior research indicates is likely to be lower than access to registration in many countries.The DHS and MICS sampling approach and data structure could also affect our results. First, there could be some measurement error as caregivers are asked whether a child’s birth is registered with the ‘civil authorities’, a term which could differ in its interpretation across countries and across survey years, especially if the physical birth certificate is not available. However, this should not affect estimates within countries. Second, the MICS and DHS data used do not include children living outside households who are more likely to be marginalised and vulnerable and also do not include information on infant deaths, especially neonatal deaths, for whom birth registration is often overlooked.Finally, there are limitations in the choice of measure to estimate inequalities: absolute differences are sensitive to changes in the number of individuals in each stratification category and to effect modification by time.However, our findings make two key contributions to prior research that documents global improvements in access to birth registration.Our findings echo prior work on how national averages can mask health inequities,In addition to the 14 countries in our sample that achieved complete birth registration and also eliminated wealth, urban/rural other inequities, 10 countries  were able to achieve a concurrent decline in non-registration and in wealth inequities. Of note, there were 6 countries  where both wealth and urban/rural inequities declined. However, it is important to note that even among this sample, improvements varied. For example, wealth inequities in Indonesia decreased on average by 1.5 percentage points per year from a 64.0 (2007) to a 56.7 (2012) percentage point difference between children in the poorest and wealthiest households. Although this decline is statistically significant, children from the poorest two wealth quintiles were still almost half as likely to be registered in 2012. In contrast, Sierra Leone achieved a 3.7 percentage point per year decline and wealth inequities fell from 52.5 (2005) to 4.7 (2013) percentage points. Both declines were significant but varied greatly in magnitude. Lessons from these countries could be instructive in understanding approaches to concurrently improve registration and reduce inequities. Further work is needed to untangle the policies and initiatives underpinning these changes, including whether this is the unintended effects of the status quo or a result of policies that were aiming to improve averages or specifically reduce inequities. A brief review of the literature indicates that the following factors can improve birth registration: reducing registration fees; linking registration to the health and education systems; expanding welfare and social protection; strengthening the design of the CRVS system ; harmonising parallel identification systems and removing policies and laws which (1) require the marriage certificates of parents to register a child, (2) require a father to be present and (3) discriminate against ethnic minorities especially in the context of providing nationality.Our findings make visible, and quantify, the large wealth and urban/rural inequities which most countries, even those that have improved birth registration, must tackle. These findings contribute to: critical scholarship on who is excluded from definitions and counts of a populationTo this end, we also show that the analysis of the birth registration indicator in national surveys provides important insights into exclusions in civil registries: health statistics from civil registries in countries with large inequities in birth registration are likely to systematically mis-estimate infant mortality rates as children from poor and rural households are less likely to be counted. However, such analyses of survey data are often based on data which are several years old and do not obviate the need for direct assessments of CRVS coverage, quality and functioning, which are current and can guide improvements. For example, the vital statistics performance index indicator, which is solely based on death registration, has been used to measure the performance of CRVS systems,Findings reveal that the wealth and urban/rural inequities in birth registration have persisted in most countries and highlight the importance of monitoring changes in equity to improve birth registration systems and to achieve SDG 16.9. Efforts to improve birth registration should strive to improve averages and actively reduce the unfair and unequal distribution of birth registration. Equity analyses can guide national policy, technical assistance to countries and provide insights into how inclusive CRVS systems are.


Object: There is an increasing interest in preoperative diffusion tensor imaging-based fiber tracking (DTI-FT) to preserve function during surgeries in motor eloquent brain regions. However, DTI tractography is challenged by inherent presumptions during particular tracking steps  and the missing “ground truth” information. In the present study, we intended to establish an objective, neurophysiology-driven approach for parameter selection during DTI-FT of the corticospinal tract integrating both imaging and neurophysiological information.Methods: In ten patients with lesions in eloquent motor areas, preoperative navigated transcranial magnetic stimulation (nTMS) was performed, followed by individual deterministic DTI-FT from a grid of cortical seed points. We investigated over 300 combinations of FA and FL thresholds and applied subsequently a multidimensional mathematical modeling of this empirical data. Optimal DTI parameters were determined by the relationship between DTI-FT  and nTMS  results. Finally, neurophysiological DTI parameters and the resulting tractography were compared to the current standard approaches of deterministic DTI fiber tracking with a 75% and 50% FA and a FL threshold of 110 mm as well as with intraoperative direct cortical and subcortical stimulation.Results: There was a good goodness-of-fit for the mathematical model  except of two cases. Neurophysiology-driven parameter selection showed a high correlation between DTI-FT and nTMS results . In comparison to the standard approach, the mathematically calculated thresholds resulted in a higher NoF in 75% of patients. In 50% of patients this approach helped to clarify the exact tract location or to detect additional functional tracts, which were not identified by the standard approach. This was confirmed by direct cortical or subcortical stimulation.Conclusion: The present study evaluates a novel user-independent method to extract objective DTI-FT parameters that were completely based on neurophysiological data. The findings suggest that this method may improve the specificity and sensitivity of DTI-FT and thereby overcome the disadvantages of current approaches. In contemporary brain tumor surgery, it is essential to obtain a comprehensive extend of resection while simultaneously preserving functionally relevant structures . The former has an important impact on survival, especially in cases of malignant brain lesions , while the latter preserves patients’ quality of life . Thus, tstarting point of descending fibers. By measuring the amplitude of the MEP, nTMS offers an additional measure for the strength of the corticospinal connection. We hypothesize a positive relationship between the NoF detected by the DTI-FT and the MEP amplitude measured with nTMS. Such a finding would justify a novel approach; specifically, selecting DTI thresholds in a way to maximize this relationship.In the present study, we suggest an advancement of the nTMS-based DTI-FT toward a purely neurophysiology-driven threshold selection. We conjecture that the current practice misses additional nTMS information beyond the mere The aim of the present study was to develop and investigate a completely neurophysiology-driven approach for parameter selection during DTI-FT of the CST, integrating both the imaging and neurophysiological information garnered from nTMS mappings.We retrospectively analyzed 10 consecutive patients  with motor eloquent lesions who underwent a nTMS in the Neurosurgical Department of the University of Tübingen. The patients were selected according to important neurosurgical indications for presurgical nTMS measurements in motor eloquent lesions . Details of clinical and demographic characteristics of the patients are depicted in a b-value of 1000 s/mm2 along 12 to 64 geometric directions. Following, the anatomical MRI data set was imported to our nTMS system  for further data acquisition and analysis  with an 8-channel head coil. Besides conventional imaging including T1-weighted (contrast-enhanced) echo sequences, DTI was performed with a single-shot spin echo at analysis , 2.We conducted nTMS using the Nexstim Eximia system  with a biphasic figure-of-eight TMS coil. After co-registration of the patient with the anatomical T1-weighted MRI by prominent anatomical landmarks, motor mapping of the lesioned hemisphere was performed. During mapping, the rMT was determined (defined as the stimulus intensity which induces at least 5/10 MEPs > 50 μV) at the EMG surface electrodes of the APB, the FD and/or the EDC muscles contralateral to the lesioned hemisphere by using the integrated EMG unit. Afterward, mapping was conducted at a stimulation intensity of 110% rMT beginning at the hot spot and continuing to the surrounding area as well as the area near to the tumor in a close grid. After manually performing artifact rejection of MEPs displaying atypical latencies, or EMG pre-activation, the nTMS data was exported into a neuro-navigation planning system  and subsequently into MATLAB  using the DICOM standard.In order to unify the cortical resolution of the individual nTMS examinations and to reduce the spatial dimensionality of the data on the cortical level, we down-sampled the individual nTMS map to a three-dimensional grid with a resolution of 1 × 1 × 1 cm see . For thiIn order to understand and to enable mathematical modeling of the multivariate relationship between FA and FL thresholds to the NoF, we performed DTI-FT for each GRID-ROI (together with the PON-ROI and PED-ROI) applying over 300 combinations of FA and FL thresholds. Therefore, we successively increased the FL values from 40 to 140 mm (in steps of 20 mm) and evaluated FA values from 0.01 to the 100% FAT (in steps of 0.03). This revealed a sigmoidal relationship between the FA values and NoF as well as between the FL values and NoF . These rx) represents NoF contingent on different FL thresholds x, and g(y) represents NoF contingent on different FA thresholds y. a, b, c, d, j, and k are constants. Finally, we modeled the 3-dimensional relation between FL and FA thresholds and NoF bywhere f and FL (0–200 mm in 5 mm steps) values for each GRID-ROI. These NoF values were then correlated (Pearson’s correlation) to the mean MEP amplitudes of the GRID-ROIs. This approach resulted in a complex multidimensional relationship with different local maxima . The locWe applied the calculated optimal FA and FL thresholds to the nTMS -ROI (together with the PON-ROI and PED-ROI) within the BrainLab software in accordance with the current clinical standard . The resFinally, in nine patients DCS and in four patients SCS were performed intraoperatively. Stimulation results were photo-documented and postoperative compared with the DTI-based determined fiber tracts due to anatomical landmarks and postoperative MRI scans , 6. In tr2) of the mathematical model for the multivariate dependency of FA, FL, and NoF as well as the Pearson’s correlation coefficient r for the relationship between NoF and MEP amplitudes. Data are shown as the mean ± standard deviation (SD), minimum, and maximum values.All statistical tests were performed using MATLAB . We analyzed the goodness-of-fit . In two cases fitting the mathematical model was insufficient .Automated neurophysiology-driven selection of optimized DTI parameters was possible in all patients. Fitting of the relationship between FA and FL threshold as well as NoF resulted in S-shaped curves. There was a good goodness-of-fit for the mathematical model in 80% (8/10) of the patients  of the patients with a sufficient goodness-of fit. Notably, on the group level, correlation results led to FL thresholds around 90 mm . HoweverThe FA threshold was higher than the 75%- and 50%-FAT in 25% (2/8) of patients. In 50% (4/8) of cases, the mathematical model resulted in a FA threshold between the 75%- and 50%-FAT. Moreover, in 25% (2/8) the mathematical model resulted in values lower than its corresponding standard FAT-values . In 37.5The graphical comparison of the fiber tracts did not show any additional information  other than an increased or decreased tract diameter in 50% of the cases . However, in 50%  our approach changed the detected tract anatomy. Here, the neurophysiology-driven approach helped to clarify the exact tract location  or detecIn the analysis of patients with a limited goodness-of fit, we detected FL thresholds <110 mm and >110 mm each in 50% (1/2) of the patients. The FA threshold was higher than the 75%- and 50%-FAT in both cases. This resulted in a NoF higher than the 75%-FAT and the 50%-FAT approach in 50%  and in a NoF lower than the 75%-FAT and the 50%-FAT approach in 50%  .There is an increasing interest in the concept of combining nTMS and DTI-FT during preoperative neurosurgical planning. In this context, the aim of our study was to investigate a neurophysiology-driven approach to FA and FL threshold selection for DTI-FT of the CST and to compare it to standard parameter selection.In regard to this goal, we demonstrate the feasibility of a completely user-independent mathematical modeling of the correlation between the NoF detected by the DTI-FT and the MEP amplitude of the nTMS, with a sufficient goodness-of-fit in 80% of the patients and a high correlation between DTI-FT and nTMS results. The individual FA thresholds differ from the postulated 75%-FAT in all patients. Importantly, in 50% of the patients the neurophysiology-driven adaptation of the DTI thresholds changes the detected tract anatomy significantly in the sense of clarifying the exact tract location or detecting additional functional tracts, which are not detected by the standard method. Notably, the presented neurophysiology-driven approach is superior in cases where standard nTMS-DTI has difficulties to detect the cortical course of fiber tracts, e.g., in a situation with an extended edema  or in a superficial but subcortical lesion. However, in 12.5% of the patients neither the standard nor our approach seems to be appropriate for DTI-FT. An improvement or modification of the mathematical model might help to overcome this drawback.In the past, several studies have shown that ROI seeding based on nTMS data resulted not only in more specific tracts with less aberrant fibers, but reduced the variability between examiners compared to the seeding approach using anatomical landmarks . In ordeIn the final comparison of fiber tracking with the nTMS-ROI as cortical region-of-interest, our automatically collected thresholds resulted in a higher NoF in 75% of the patients compared to the arbitrary thresholds of 75%-FAT and FL threshold of 110 mm. Considering the known underestimation of fibers in the cortex region in DTI algorithms , our appAlongside other DTI tractographies, the suggested neurophysiology-driven approach still lacks ground truth information and may only reduce, but not avoid, false positive or false negative tracts, e.g., due to the crossing and “kissing fiber” problem . TherefoThis present study is the first to introduce a standardized and nTMS-based threshold selection for DTI-FT. Implementation and further exploration of this approach could overcome some of the current limitations of concurrent DTI-TMS approaches and ultimately result in an improvement of neurosurgical planning.The datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by the local ethics committee, Eberhard Karls Universität Tübingen. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.KMa contributed to the acquisition, analysis, and interpretation of data and writing of the first draft. LT, MTL, ML, KMo, BB, UE, AG, and MT contributed to the data acquisition, interpretation of data, and the review and critique of the final manuscript. GN was responsible for the conception, design, data acquisition, analysis, and interpretation as well as the review and critique of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Low Birth Weight (LBW) is a serious public health concern in low- and middle-income countries. Globally, 20 million, an estimated 15% to 20% of babies were born with LBW, and, of these, 13% were in sub-Saharan Africa. Although the World Health Assembly targeted to reduce LBW by 30% by the end of 2025, little has been done on and known about LBW. To meet the goal successfully and efficiently, more research studies on the problem are vital. Hence, the aim of this study was to determine the prevalence and the associated factors of LBW in Dire Dawa city, eastern Ethiopia.  The purpose of this study was to assess the prevalence and the associated factors of low birth weight in Dire Dawa City, eastern Ethiopia, 2017. p value less than 0.05 was considered as statistical significant.  A cross-sectional study designed was conducted, and using a systematic sampling technique, 431 mothers who gave birth in the public hospitals in Dire Dawa city from July 01 to August 30, 2018, were selected. Stillbirth and infants with birth defects were excluded from the study. Well-trained data collectors collected the data using a structured questionnaire which was pretested. The data were analyzed using SPSS Version 22.0. The Adjusted Odds Ratio (AOR) with 95% confidence interval (CI) was applied in multivariate logistic regression models, and  The prevalence of low birth weight was 21%. Not received nutritional counseling during antenatal care , preterm birth , maternal smoking , and height of the mother less than 150 cm  were significantly associated with Low birth weight.  There was a high prevalence of low birth weight in the study area. Effective dietary counseling and additional diet, implementing proven strategies to prevent preterm birth and avoid smoking during pregnancy might decrease the low birth weight and then enhance child survival. The burden of low birth weight (LBW) is a serious public health concern in low- and middle-income countries , 2. GlobThe World Health Organization (WHO) defines LBW as a birth weight of less than 2,500 grams . LBW conIn multiple studies, different factors have been identified as determinant for LBW, and among these are young maternal age at pregnancy, birth order, the family's income, maternal undernutrition, maternal underweight, pregnancy-related complications, preterm birth, chronic medical illness, multiple pregnancies, history of previous LBW, insufficient prenatal care, and maternal smoking –22.In Ethiopia, the issue of LBW and the factors influencing it have not received much attention. However, the country is with very high neonatal mortality due to factors associated with LBW and are one of the critical issues that cause babies to suffer from short-term and long-term health consequences and mortality –26.Although LBW has been reported to account for perinatal morbidity and mortality and extensively explored in developed countries, in developing countries, including Ethiopia, few studies are available on LBW. In order to prevent LBW, an understanding of its main modifiable risk factors is essential, so that health managers and practitioners may use for plan strategies and implement appropriate interventions toward promoting health , 27. HenAn institutional-based cross-sectional study design was conducted in Dire Dawa City Administration. It is located 515 kilometers away from Addis Ababa, the capital of Ethiopia. According to the 2007 Ethiopian census, an estimated 3,96,423 people were living in the administration. It has achieved 100% primary health care access. In terms of the distribution of health facilities, there are 2 governmental and 4 private hospitals, 8 health centers, 5 higher clinics, and 12 medium clinics in the city. Mothers who gave birth in Dilchora Referral Hospital and Sabina Primary Hospital from July to August 2018 were included. According to the Dire Dawa City Administration's health office report, approximately about 2000 live births happened every two months in the administration and 58.7% of delivery took place in the health facilities (26). The two hospitals were included because more than two-thirds (1260) of the delivery takes place in these facilities. Stillbirth and infants with birth defects were not included in this study.n = (Zα/2)2pq/d2) by considering the proportion of LBW in eastern Ethiopia 21.9% [K) was three. The initial mother was employed using the lottery method. When the selected study subject did not fulfill the inclusion criteria, the subsequent mother was included.The sample size was determined using a single population proportion formula  and then translated back into English for checking the consistency by different language expertise. Trained midwives and nurses working in the labour ward conducted the interview and anthropometric measurements. The weight of the newborns was measured within the first hour of birth using a balanced Seca scale. The measurement scale was always checked and calibrated before weighing each newborn. Maternal height was measured against a wall using a height scale to the nearest centimeter, and maternal weight was measured by using a beam balance to the nearest kilogram. To ensure the quality of the data, a two-day intensive training was given for all the supervisors and the data collectors. The data collection process was undertaken with frequent monitoring and supervision. Finally, double data entry was done to check the consistency of the data and minimize the entry errors.Birth weight: the first weight of the newborns measured within the first hour after birth. Low birth weight was for those newborns who weighed less than 2500 g, while those newborns with a birth weight of 2500 g and above were considered of normal birth weight.p value <0.2 were retained and entered into the multivariable logistic regression analysis. Hosmer and Lemeshow goodness-of-fit tests were used to assess whether the necessary assumptions were fulfilled. Adjusted odds ratio (AOR) with 95% confidence intervals (CI) was used. A p value <0.05 was considered statistically significant.The data were coded, entered into EPI data Version 3.1, and exported to SPSS Version 22.0 software for analysis. Then, they were summarized and presented using descriptive statistics. The outcome variables were coded as “1” for LBW whereas “0” for others. The association between the outcome variables  and the independent variables was analyzed using a binary logistic regression model. The covariates which had a Before the data collection, ethical permission was obtained from the ethical review committee of the College of Medicine and Health Science in Dire Dawa University, and informed written consent was obtained from the participants before conducting the interview and the measurement.Four hundred and twenty mothers were included in the study, with a response rate of 97.40%. The mean (±SD) age of the mothers was 27.4 (±4.98) years. More than half of the study participants, 245 (58.3%), were in the age group of 20–34 years, followed by the age group of above 30 years, 142 (33.8%). Three hundred and seventy-six (89.5%) mothers were married. Regarding religious distribution, 242 (57.6%) were Muslim, and 119 (28.3%) were Orthodox Christians .Out of the total participants, 245 (53.3%) had 2–4 children. About a quarter of the mothers (26.1%), 67(23.3%), and 41(14.3%) had a history of abortion, stillbirth, and previous LBW, respectively.Among the respondents who delivered in governmental hospitals, 320 (76.2%) had planned pregnancy. Most of the respondents, 395 (95%), had singleton babies. Two hundred and ninety-six (70.5%) of the mothers had attended antenatal care (ANC) visits. One hundred and thirty-four (45.3%) of them had less than four ANC visits. More than half (54.7%) of the ANC attendants had four or more ANC follow-ups. Among the ANC attendants, 277 (93.6%) had utilized iron, and of them, 32.1% had taken iron for four or more months during pregnancy. About 241 (81.4%) of the mothers had been vaccinated for tetanus toxoid, of whom 48% were vaccinated only once. Three hundred and ninety-one (93.1%) of the respondents were human immunodeficiency virus (HIV) negative, while only 29 (6.9%) were HIV positive. Among the respondents, 191 (45.5%) had used contraceptive methods preceding the current pregnancy. The level of hemoglobin among the mother was below 7, 8–11, and 12 or above gm/dl for 3.8%, 57.45%, and 38.8%, respectively .From the total newborns, 21% had LBW while 79% were at or above 2500 grams. The mean birth weight of the newborns was 3002 gm ± 709.2 grams .Three hundred and eighty-three (91.2%) of the mothers had delivered at or after 37 weeks of gestation. Three hundred and sixty-nine (87.9%) of the newborns had an APGAR  score of seven and above, whereas 51 (12.1%) had less than seven within the first minute. More than half (53.3%) of the newborns were female. Two hundred and fifteen (51.2%) of the mothers had given birth through the spontaneous vaginal delivery . The typMost of the respondents, 216 (92.7%), had a weight of 50 kilograms and above for this pregnancy. Three hundred and ninety-nine (95%) of them had a height of 150 centimeter and above. More than two-thirds (72.1%) of the mothers' Mid-Upper Arm Circumference (MUAC) was above 22 centimeters. Most of the mothers did not smoke (92.9%) and drink alcohol (95%) during pregnancy .In the multivariable analysis, the factors significantly associated with LBW were not received dietary counseling during ANC, preterm birth, maternal smoking during pregnancy, and maternal height. The mothers who did not receive nutritional counseling during ANC follow-up were 2 times  more likely to give LBW baby compared with their counterparts. Furthermore, the neonates who were delivered before 37 weeks of the gestational age were 18 times  more likely to be LBW compared with the neonates delivered at or above 37 weeks of gestation. The pregnant women who were smoking during pregnancy were nearly 4 times  more likely to deliver LBW babies compared with their counterparts. In addition, the mothers whose height was less than 150 centimeters  had about four times the chance of delivering LBW babies than those with height greater than 150 centimeters .In the present study, the prevalence of LBW was 21% . In the multivariable analysis, not received dietary counseling during ANC, preterm birth, maternal smoking during pregnancy, and maternal height were significantly associated with LBW. The mean weight of the newborns was 3002 ± 709.2 grams. The prevalence of LBW in this study was higher than the ones found in studies conducted in Italy (11.8%), Brazil (7.6%), Iran (5.2%), Kenya (12%), and Malaysia (13.96%) –33. ThisHowever, the finding of this study is consistent with the ones reported from Uganda (25.5%), Tanzania (21%), and Ethiopia , 38. It The mothers who did not receive nutritional counseling during the time of ANC follow-up were more likely to deliver LBW babies compared with the mothers who had received nutritional counseling during ANC follow-up. This is the fact that counseling about nutrition has increased the awareness of pregnant women on nutrition at the time of pregnancy . This fiAs per this study, preterm newborns were more likely to be LBW compared with newborns delivered at or above 37 weeks of gestation. The finding of this study was congruent with those findings of studies conducted in Uganda, Kenya, Zimbabwe, and Ethiopia , 43, 44.Smoking habits during pregnancy were significantly associated with LBW. The newborns who were delivered by mothers who had always smoked during pregnancy were more likely to be LBW compared with those from nonsmoking mothers. This is in line with the findings in Switzerland and Tanzania , 31, 48.This study used a probability sampling procedure to select the study participants. We used the questionnaire method and anthropometric measurement (height and weight) to assess LBW. Since the study was cross sectional, it was not possible to strongly demonstrate cause and effect relationships. We used self-reporting (interview response) which might have social desirability bias. Some questions also required the participant's recall, which could have affected the results, as most of them could have forgotten.The prevalence of LBW in the study area was high. The mothers who did not receive nutritional counseling during ANC, preterm birth, babies from smoking mothers, and maternal height were associated with LBW. Effective dietary counseling and additional diet, implementing proven strategies to prevent preterm birth and avoid smoking during pregnancy, would improve the birth weight of the newborn, enhance child survival, and reduce child morbidity and mortality.