Precise Staging Research Articles

보이스코일모터를 이용한 초정밀 자기부상 스테이지

Voice coil motor is an actuator that employs a non-contact electromagnetic force between its coils and magnets, and is widely used in precision stages on account of its good linearity between current and force. Additionally, these advantages are beneficial for implementing the magnetic levitation mechanism. Unlike the case of general use of a voice coil motor where 1-DOF translational motion is applied, 6-DOF magnetic levitation causes variation in the relative position and orientation between the coil and the magnet. Accordingly, the force constant also changes. In this study, high-level precision positioning of 20 ㎚ was realized through the design and control of a magnetic levitation stage using voice coil motors. In the process, the change in the force of the voice coil motor was found to be approximately 1% within the range of motion. Therefore, the proposed design was verified to be suitable for high-precision stages.

Lipidomics as Tools for Finding Biomarkers of Intestinal Pathology: From Irritable Bowel Syndrome to Colorectal Cancer.

Lipidomics is an emerging and promising omic that analyzes different lipid molecules in a biological sample. It is considered as a branch of metabolomics, which is defined as the comprehensive analysis of metabolites in a biological specimen. Nonetheless, in recent years lipidomics is being considered a distinct discipline in the biomedicine field. Lipids play important roles in many biological pathways and could work as biomarkers of disease or as therapeutic targets for treatment diseases. The major lipidomics strategies are shotgun lipidomics and liquid chromatography coupled with mass spectrometry. Gastrointestinal diseases such as irritable bowel syndrome or inflammatory bowel disease are chronic diseases that need non-invasive biomarkers for prognosis and diagnosis. Even more, patients with inflammatory bowel disease are at a significantly increased risk of colorectal cancer, principally resulting from the pro-neoplastic effects of chronic intestinal inflammation. Current screening methods utilized globally include sigmoidoscopy, or standard colonoscopy but it is important to develop non-invasive and accurate screening tools to facilitate early detection and precise staging of colorectal cancer. Disease progression and response to treatment may benefit also from the application of these potential new tools. This review is focused on studies that use lipidomics approaches to discover potential biomarkers for monitoring the mentioned intestinal diseases and, particularly, tumour progression.

Imaging of Oligometastatic Disease.

Simple SummaryThe imaging of oligometastatic disease (OMD) is challenging as it requires precise loco-regional staging and whole-body assessment. The combination of imaging modalities is often required. The more accurate imaging tool will be selected according to tumor type, the timing with regard to measurement and treatment, metastatic location, and the patient’s individual risk for metastasis. The most commonly used modalities are contrast-enhanced computed tomography (CT), magnetic resonance imaging and metabolic and receptor-specific imaging, particularly, 18F-fluorodesoxyglucose positron emission tomography/CT, used alone or in combination.Oligometastatic disease (OMD) is an emerging state of disease with limited metastatic tumor burden. It should be distinguished from polymetastatic disease due the potential curative therapeutic options of OMD. Imaging plays a pivotal role in the diagnosis and follow-up of patients with OMD. The imaging tools needed in the case of OMD will differ according to different parameters, which include primary tumor type, timing between measurement and treatment, potential metastatic location and the patient’s individual risk for metastasis. In this article, OMD is defined and the use of different imaging modalities in several oncologic situations are described in order to better understand OMD and its specific implication for radiologists.

Development of Projection X-ray Microscope with 100 nm Spot Size

A projection X-ray microscope useful for industrial non-destructive inspections and various biological observations has been developed. By installing a Schottky type electron source, a nano focus X-ray source with 100 nm focal spot size that is easy to handle in various laboratories is successfully achieved at 20 to 80 kVp. An imaging system has been composed of a vertical type that can adjust a sample position on the optical axis, and high-resolution imaging can be achieved by using a high precision stage unit. A test chart with 200 nm line width can be clearly confirmed by a transmission image, and CT images with high spatial resolution were also obtained for a test sample of glass containing air micro-bubbles. Finally, we confirmed that the spatial resolution of the obtained CT images does not contradict the measurement conditions by using the evaluation formula of spatial resolution including the effect of X-rays diffraction.

Self-calibrated 3D differential phase contrast microscopy with optimized illumination.

3D phase imaging recovers an object's volumetric refractive index from intensity and/or holographic measurements. Partially coherent methods, such as illumination-based differential phase contrast (DPC), are particularly simple to implement in a commercial brightfield microscope. 3D DPC acquires images at multiple focus positions and with different illumination source patterns in order to reconstruct 3D refractive index. Here, we present a practical extension of the 3D DPC method that does not require a precise motion stage for scanning the focus and uses optimized illumination patterns for improved performance. The user scans the focus by hand, using the microscope's focus knob, and the algorithm self-calibrates the axial position to solve for the 3D refractive index of the sample through a computational inverse problem. We further show that the illumination patterns can be optimized by an end-to-end learning procedure. Combining these two, we demonstrate improved 3D DPC with a commercial microscope whose only hardware modification is LED array illumination.

Non-invasive precise staging of liver fibrosis using deep residual network model based on plain CT images.

The aim of this study was to explore the application of five-class deep residual network models based on plain CT images and clinical features for the precise staging of liver fibrosis. This retrospective clinical study included 347 patients who underwent liver CT, with pathological staging of liver fibrosis as the gold standard. We established three ResNet models to stage liver fibrosis. The output diagnosis labels of models were 0, 1, 2, 3 and 4, which correspond to F0, F1, F2, F3, and F4 stages. Confusion matrices were used to evaluate the performances of models to precisely stage liver fibrosis. The performance for diagnosing cirrhosis (F4), advanced fibrosis (≥ F3) and significant fibrosis (≥ F2) of models was evaluated with receiver operating characteristic (ROC) analyses. The kappa coefficients of the five-class ResNet model (based on plain CT images), the five-class ResNet clinical model (based on clinical features), and the five-class mixed ResNet model (based on plain CT images and clinical features) for precise staging liver fibrosis were 0.566, 0.306, and 0.63, respectively. The recall rates and precision rates for F0, F1, F2, and F3 of three models were lower than 60%. The ROC AUC values of the five-class ResNet model, the five-class ResNet clinical model, and the five-class mixed ResNet model for diagnosing cirrhosis, advanced fibrosis, and significant fibrosis were 0.95, 0.88, and 0.82, 0.80, 0.72, and 0.70, 0.95, 0.90, and 0.83, respectively. The five-class ResNet models are of high value in the diagnosis of liver cirrhosis, advanced liver fibrosis, and significant liver fibrosis. However, for the precise staging of liver fibrosis, the models cannot accurately distinguish other liver fibrosis stages except F4. Plain CT images combined with clinical features have the potential to improve the performance of the ResNet models in diagnosing liver fibrosis.

Surgeon-Pathologist Team Approach Dramatically Affects Lymph Nodes Detection and Improves Patients' Short-Term Outcome.

Simple SummaryAppropriate lymph node harvesting for patients with gastric cancer is fundamental for a correct staging and is strongly related to survival. In this study, we present a new protocol for on-site macroscopic evaluation and sampling of lymph nodes for gastric cancer patients. With the joint collaboration of surgeons and pathologists, our method aims to provide the largest possible number of analyzed lymph nodes per patient, allowing for a better staging. We are convinced that this approach is routinely feasible, and our preliminary results seem to confirm better patient stratification compared to other lymph node dissection methods.The downstaging of gastric cancer has recently gained particular attention in the field of gastric cancer surgery. The phenomenon is mainly due to an inappropriate sampling of lymph nodes during standard lymphadenectomy. Hence, collection of the maximum number of lymph nodes is a critical factor affecting the outcome of patients. None of the techniques proposed so far have demonstrated a real efficiency in increasing the number of identified lymph nodes. To harvest the maximum number of lymph nodes, we designed a protocol for on-site macroscopic evaluation and sampling of lymph nodes according to the Japanese Gastric Cancer Association protocol. The procedure was carried out by a surgeon/pathologist team in the operating room. We enrolled one hundred patients, 50 of whom belonged to the study group and 50 to a control group. The study group included patients who underwent lymph node dissection following the proposed protocol; the control group encompassed patients undergoing standard procedures for sampling. We compared the number and maximum diameter of lymph nodes collected in both groups, as well as some postoperative variables, the 30-day mortality and the overall survival. In the study group, the mean number of lymph nodes harvested was higher than the control one (p = 0.001). Moreover, by applying the proposed technique, we sampled lymph nodes with a very small diameter, some of which were metastatic. Noticeably, no difference in terms of postoperative course was identified between the two groups, again supporting the feasibility of an extended lymphadenectomy. By comparing the prognosis of patients, a better overall survival (p = 0.03) was detected in the study group; however, to date, no long-term follow-up is available. Interestingly, patients with metastasis in node stations number 8, 9, 11 or with skip metastasis, experienced a worse outcome and died. Based on our preliminary results, the pathologist/surgeon team approach seems to be a reliable option, despite of a slight increase in sfaff workload and technical cost. It allows for the harvesting of a larger number of lymph nodes and improves the outcome of the patients thanks to more precise staging and therapy. Nevertheless, since a higher number of patients are necessary to confirm our findings and assess the impact of this technique on oncological outcome, our study could serve as a proof-of-concept for a larger, multicentric collaboration.

원형 노치를 갖는 원통형 플렉셔 힌지의 해석

Flexure hinges are widely used as joint linkages for precision stages applied to lithography processes. Among them, precision stages with 3 DOF (Degrees of Freedom) of x, y and θSUBz/SUB prevail in semiconductor manufacturing and they have been adopting single directional flexure hinges as mechanical linkages without backlash and debris. However, new technologies including nano-imprinting, which replaces lithography, needs more than 3 DOF precision positioning stages that adopt cylindrical flexure hinges. In this study, the cylindrical flexure hinges with circular notches were analyzed using the Timoshenko beam theory and FEM (Finite Element Method), with focused on their directional stiffness. Based on the analysis and result comparison between theoretical equations and FEM, several practical suggestions for determining important design variables are provided in the conclusion of this study.

Setup for photolithography on microscopic flakes of 2D materials by combining simple-geometry mask projection with writing.

An optical arrangement and procedure for photolithography on microscopic flakes of two-dimensional materials with an arbitrary shape/size is described. The technique combines projection of demagnified images of simple geometry macroscopic masks with writing. Only a few masks, such as vertical/horizontal slit and square hole, are sufficient to generate most of the required patterns. The setup allows for initially locating the photoresist coated flake on a substrate by imaging it. Thereafter, the automated precise sample stage motion followed by projection of the demagnified mask image is repeated several times to expose the photoresist in the shape of the required pattern. Appropriate light wavelength regimes for imaging and for exposure are chosen through automated optical filter switching. Programming steps for the process are described. The setup allows for direct lithography in one round on microscopic samples without requiring sample shape/size specific masks or predefined position markers. Making of electrode lines of width down to 3 μm, at desired locations on tiny flakes of MoS2, is demonstrated.

The importance of precise staging of axilla in patients with breast cancer in order to avoid unnecessery ALND

Background: Avoiding ALND in the absence of metastatic disease in the axillary lymph nodes is a priority of modern breast cancer surgery.The aim of this paper is to point out the insufficiency of palpation as an traditional method of axillary examination and mandatory consideration of radiological, primarily US, findings on the status of ipsilateral axillary lymph nodes.

ANALISIS KEMAMPUAN BERPIKIR GEOMETRI BERDASARKAN TAHAP BERPIKIR VAN HIELE PADA PEMBELAJARAN MATEMATIKA SISWA SMP

Geometry is a mathematical branch that deals with the shape of an object, the spatial relationship between various objects, and its properties. Learning geometry is essential to supporting logical thinking ability, perceptual intuition, and reading and interpreting mathematical arguments. But many middle school students do not reach the stage of deduction and precision. The research was to analyze a high school student's geometry ability based on Van Hiele's stages of thinking. They consist of five levels of visualizing, analysis, sequence, deduction, and precision. It is a type of qualitative study with a descriptive method. The sample consisted of 20 eighth-graders in the located in the Karawang district. Data collection is carried out using a written questionnaire and test. Research shows that stage-0 (visualization) is the student's most achievable point from a questionnaire at 55% and a written test of 65%. The third stage (deduction) and fourth (accuracy) are the most difficult for students to achieve, based on written tests only 9% of students reach the third stage and only 6% of students reach the fourth. Student difficulties in learning this geometry may be due to several factors in their understanding of prerequisite materials, ability to concepts and pale-building qualities is lacking, and limited skill in using geometry ideas to solve mathematical problems.

Interpretation of biopsy material after transuretral and laser en bloc resection of non-muscle-invasive bladder cancer

Bladder cancer is one of the most common onco-urological diseases, ranked second in frequency among all tumors of the urinary system after prostate cancer. At the time of detection of the primary tumor, approximately 75% of patients have no invasion into the muscularis layer (non-muscle-invasive carcinoma), with tumor growth limited to the basal membrane (stage Ta) or submucosal base (stage T1). Removal of the tumor in a «unified block» (laser en-bloc resection or L-ERBT), unlike routine transurethral resection, allows to obtain qualitative biopsy material for precise pathomorphological staging of the tumor process. In order to accurately stratify a patient into one or another risk group, verification of the following morphological parameters is required: degree of tumor differentiation and its malignancy, depth of invasion, foci of carcinoma in situ at resection margins, presence or absence of lymphovascular invasion. Identification of tumor variant histology is also recommended. Information on presence or absence of detrusor elements in the specimen is necessary in the morphological report, as this parameter is considered as a criterion of radically performed tumor removal. According to ICCR recommendations (International Collaboration on cancer reporting), it is recommended to use subclassification of T1 stage using all possible criteria: volume and/or depth of invasion (assessed in mm), and/or width of invasion «spot» (assessed in mm), and/or involvement of anatomical structure - muscularis mucosae. Full morphological examination of the material obtained during the primary resection of the tumor is an important step in the diagnosis and treatment of bladder cancer, as it allows to stratify the patient into one or another risk group and, accordingly, allows to develop a personalized postoperative management.

Site Selection of Precast Concrete Component Factory Based on PCA and GIS

In China, with the expansion of the prefabricated construction market, the demand for precast concrete (PC) components is increasing and the construction of production plants to meet this need is expanding. To address the problem of siting PC component plants in China's construction industry, a combination of qualitative and quantitative analysis using principal component analysis (PCA) and geographic information system (GIS) is proposed for their siting. Taking the site selection process of a PC component plant in Wuhan, Hubei Province, China as an example, the diamond model is combined with six dimensions of environmental factors, requirements, regional competition, related and supporting industries, technological innovation and policies and regulations to construct an indicator system for PC component plant site selection. In the preliminary selection stage, PCA was applied to analyze the site selection indexes to obtain the overall score and ranking of each district for the selection of PC component plants in Wuhan, and it was concluded that three districts, namely, Xinzhou, Hannan, and Huangpi, were more suitable for the construction of component plants. In the precise selection stage, based on the availability of data, Hannan was selected among the three areas suitable for site selection for GIS analysis, using the visual‐spatial analysis function of GIS to quantify the four geographical information indicators of environmental factors, and the results showed that Area C in Hannan was the most suitable area. The results show that the method has high accuracy and good applicability.

Application of U-Pb dating technique in the study of hydrothermal activities of dolomite reservoir: A case study on 3<sup>rd</sup> member of Yingshan Formation in Gucheng area, Tarim Basin, NW China

古城地区是塔东探区的重点勘探区块，下奥陶统鹰三段是塔东探区首要的勘探层系。探寻多期热液作用改造后的优质白云岩储层是扩大研究区勘探成果的关键。本文在储层岩石学特征判识的基础上，应用U-Pb同位素定年技术，结合碳氧锶镁同位素和稀土元素分析测试，分析了热液性质，明确了热液作用发生的确切时期及期次，探讨了热液作用对白云岩储层的影响。研究结果表明，古城地区鹰三段白云岩储层发育准同生-浅埋藏海水成因的粉晶-中晶白云岩及热液作用产物。热液作用可划分为二期：第一期为中-晚奥陶世贫镁热液，表现为鞍状白云石充填缝洞及重结晶次生加大的粗晶白云石，U-Pb测定年龄为464±12Ma到473.9±9.1Ma，氧同位素值比早奥陶世正常海相白云石明显偏负，锶同位素比值明显高于早奥陶世海水值，稀土元素Eu正异常，锶、铁、镁元素含量低；第二期为晚奥陶世-早志留世钙质热液，表现为方解石充填缝洞及对先存白云石的溶蚀，U-Pb测定年龄为448±15Ma到457.4±6.6Ma，氧锶同位素组成严重偏离同时期正常海相白云石范围，轻稀土元素明显富集，Eu正异常，锶、钙元素含量高，锰元素含量低。第二期热液作用是白云岩储层溶蚀的关键，同期NNE向断裂带作为其输导系统，是优质储层发育的有利部位，为有利区带预测提供依据。;The dolomite in 3^rd member of Yingshan Formation in Gucheng area is a significant exploration field in the east of Tarim Basin. High-quality dolomite reservoir reworked by hydrothermal activities is the key to expand exploration. Based on petrographic characteristics, this paper analyzed hydrothermal properties, clarified the precise dating and stages of hydrothermal process, and discussed hydrothermal effects on dolomite reservoir using U-Pb dating technique, combined with analysis of carbon and oxygen, strontium, magnesium isotopes and rare earth elements. The study shows that micrite-medium grained dolomites taken place in paracontemporaneous-shallow buried phase and hydrothermal products in research area. There are two stages of hydrothermal processes. The first stage hydrothermal process is very low in magnesium content in the Middle-Late Ordovician, at the result of saddle dolomite filling in fractures/vugs and coarse dolomite formed by recrystallization aged 464±12Ma~473.9±9.1Ma by U-Pb dating with oxygen isotope negative compared with normal marine dolomite, strontium isotope values higher than Early Ordovican sea values and positive Eu anomalies. The contents of strontium, ferrum and magnesium are relatively low. The second stage hydrothermal process is high in calcium content in the Late Ordovician-Early Silurian, at the result of calcite filling in fractures/vugs and dissolution of existing dolomites, aged 448±15Ma~457.4±6.6Ma by U-Pb dating with significantly negative oxygen isotope and enriched LREE and positive Eu anomalies. The strontium content is high while manganese content is low. Migration pathway of the second stage hydrothermal process as a key of dolomite reservoir dissolution is NNE fracture zones developing high-quality reservoir, which provides a basis for the prediction of favorable zones.

Renal tumours of childhood: A review

Renal tumours of childhood are rare, although they are one of the most common solid tumours in children. They include numerous entities, which have different clinical, histological, molecular biological and prognostic features, so their precise diagnosis and staging are critical for appropriate treatment. The most common is Wilms' tumour (WT) with ~80-85 % of all cases, whereas other entities including mesoblastic nephroma, clear cell sarcoma, rhabdoid tumour, renal cell carcinoma, metanephric tumours and others are very rare (2-4 % each) which explains why they represent a big diagnostic challenge for diagnostic pathologists. They are subclassified into three risk groups - low, intermediate and high - which have different treatments and prognosis. There are two big study groups which have different approaches but remarkable similar outcomes. The International Society of Paediatric Oncology approach (followed in most of the world) is based on preoperative chemotherapy, followed by surgery and further therapy, whereas the Children's Oncology Group approach (followed mainly in the United States and Canada) is based on primary surgery, followed by postoperative treatment.

Design of a Precise Positioning Stage Actuated by a Double-Layer Stick-Slip Actuator Used for Precise Assembly

Design of a Precise Positioning Stage Actuated by a Double-Layer Stick-Slip Actuator Used for Precise Assembly

Dynamically taming focal fields of femtosecond lasers for fabricating microstructures

Micromachining based on femtosecond lasers usually requires accurate control of the sample movement, which may be very complex and costly. Therefore, the exploration of micromachining without sample movement is valuable. Herein, we have illustrated the manipulation of optical fields by controlling the polarization or phase to vary periodically and then realized certain focal traces by real-time loading of the computer-generated holograms (CGHs) on the spatial light modulator. The focal trace is composed of many discrete focal spots, which are generated experimentally by using the real-time dynamically controlled CGHs. With the designed focal traces, various microstructures such as an ellipse, a Chinese character “Nan”, and an irregular quadrilateral grid structure are fabricated in the z-cut LiNbO3 wafers, showing good qualities in terms of continuity and homogeneity. Our method proposes a movement free solution for micromachining samples and completely abandons the high precision stage and complex movement control, making microstructure fabrication more flexible, stable, and cheaper.

Study of Non-alcoholic Fatty Liver Disease (NAFLD) by Shear-wave Elastoraphy in Subjects with Metabolic Syndrome

Background: Non-alcoholic fatty liver disease (NAFLD) is well known to have a strong association with metabolic syndrome. The degree of liver fibrosis is related to the clinical course and prognosis. Shear-wave elastography (SWE) provides a precise non-invasive staging of the degree of liver fibrosis in NAFLD. 
 Aims and objectives: To study Non-alcoholic fatty liver disease (NAFLD) by Shear-Wave Elastography (SWE) in subjects with metabolic syndrome (MetS).
 Material and methods: This was a single centre, retrospective, comparative study done on patients with MetS in 100 in a tertiary care hospital over period of 18 months from October 2019 to March 2021. Enrolled patients underwent conventional ultrasonography (USG), point SWE (pSWE), fasting blood sugar, post-prandial blood sugar, glycosylated HbA1c, lipid profile, LFTs. Appropriate statistical tests were applied using SPSS v21 for analysis and p-value<0.05 was considered statistically significant.
 Results: Mean age was 55.8 (SD±15.34). Majority belonged to age group 51-65 years (33%). Grade 3 fatty liver (steatosis) on USG had 3.39 times independently (OR:3.39,p=0.043) more chance of having significant fibrosis or cirrhosis(F3-F4) by SWE over those who do not have fatty liver (steatosis) on USG. Those with 4 components of MetS had 6 times (OR:6.04,p=0.003) and those with 5 components had 13.7 (OR:13.768,p=0.001) times more chance of having significant fibrosis or cirrhosis(F3-F4) by SWE over those who have 3 components independently.
 Conclusion: Increasing number of components of MetS and steatosis (fatty liver grade) on USG were independently associated with higher grades of fibrosis by SWE.

Dynamic Contact Angle Measurement on a Microscopic Area and Application to Wettability Characterization of a Single Fiber.

Dynamic contact angles on a microscopic area were measured using a specially developed system. Combining pulse injection equipment, a high-speed image capture system set on a microscope, and precise positioning stages, contact angles of typically 2 nL water droplets were measured at a repetition rate of 130 ms. Thereafter, measuring the series of the contact angles of a droplet on a planar silicon surface, contact angle hysteresis, defined as the difference between the advancing and receding contact angles, was measured, and the effect of droplet size was clarified. The system was then applied to characterize a single fiber wherein the contact angles of droplets suspended on a polypropylene fiber, typically 19 μm in diameter, were measured. Plasma treatment is often adopted to modify wettability and has directionality. By fixing a fiber while applying torsion and changing the measurement position along the fiber, the contact angles at different circumferential positions can be characterized. This effect was unraveled by comparing the contact angles on the treated side to its opposite side as well as the effect of fiber diameter.

Heterogeneity of beta-cell function in subjects with multiple islet autoantibodies in the TEDDY family prevention study - TEFA

BackgroundIndividuals with multiple islet autoantibodies are at increased risk for clinical type 1 diabetes and may proceed gradually from stage to stage complicating the recruitment to secondary prevention studies. We evaluated multiple islet autoantibody positive subjects before randomisation for a clinical trial 1 month apart for beta-cell function, glucose metabolism and continuous glucose monitoring (CGM). We hypothesized that the number and type of islet autoantibodies in combination with different measures of glucose metabolism including fasting glucose, HbA1c, oral glucose tolerance test (OGTT), intra venous glucose tolerance test (IvGTT) and CGM allows for more precise staging of autoimmune type 1 diabetes than the number of islet autoantibodies alone.MethodsSubjects (n = 57) at 2–50 years of age, positive for two or more islet autoantibodies were assessed by fasting plasma insulin, glucose, HbA1c as well as First Phase Insulin Response (FPIR) in IvGTT, followed 1 month later by OGTT, and 1 week of CGM (n = 24).ResultsAutoantibodies against GAD65 (GADA; n = 52), ZnT8 (ZnT8A; n = 40), IA-2 (IA-2A; n = 38) and insulin (IAA; n = 28) were present in 9 different combinations of 2–4 autoantibodies. Fasting glucose and HbA1c did not differ between the two visits. The estimate of the linear relationship between log2-transformed FPIR as the outcome and log2-transformed area under the OGTT glucose curve (AUC) as the predictor, adjusting for age and sex was − 1.88 (− 2.71, − 1.05) p = 3.49 × 10–5. The direction of the estimates for all glucose metabolism measures was positive except for FPIR, which was negative. FPIR was associated with higher blood glucose. Both the median and the spread of the CGM glucose data were significantly associated with higher glucose values based on OGTT, higher HbA1c, and lower FPIR. There was no association between glucose metabolism, autoantibody number and type except that there was an indication that the presence of at least one of ZnT8(Q/R/W) A was associated with a lower log2-transformed FPIR (− 0.80 (− 1.58, − 0.02), p = 0.046).ConclusionsThe sole use of two or more islet autoantibodies as inclusion criterion for Stage 1 diabetes in prevention trials is unsatisfactory. Staging type 1 diabetes needs to take the heterogeneity in beta-cell function and glucose metabolism into account.Trial registrationClinicalTrials.gov identifier: NCT02605148, November 16, 2015