The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

“Unpaired Image-to-Image Translation using Cycle-Consistent Adversarial Networks”の学習報告

1. Type 1 diabetes (due to b-cell destruction, usually leading to absolute insulin deficiency) 2. Type 2 diabetes (due to a progressive insulin secretory defect on the background of insulin resistance) 3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the second or third trimester of pregnancy that is not clearly overt diabetes) 4. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young [MODY]), diseases of the exocrine pancreas (such as cystic fibrosis), and drugor chemical-induced diabetes (such as in the treatment of HIV/AIDS or after organ transplantation)

Classification and diagnosis of diabetes

PEEK Biomaterials in Trauma, Orthopedic, and Spinal Implants

Generative adversarial network in medical imaging: A review.

We studied the morphometry of 35 femora from 31 female patients with developmental dysplasia of the hip (DDH) and another 15 from 15 age- and sex-matched control patients using CT and three-dimensional computer reconstruction models. According to the classification of Crowe et al 15 of the dysplastic hips were graded as class I (less than 50% subluxation), ten as class I/III (50% to 100% subluxation) and ten as class IV (more than 100% subluxation). The femora with DDH had 10 to 14 degrees more anteversion than the control group independent of the degree of subluxation of the hip. In even the most mildly dysplastic joints, the femur had a smaller and more anteverted canal than the normal control. With increased subluxation, additional abnormalities were observed in the size and position of the femoral head. Femora from dislocated joints had a short, anteverted neck associated with a smaller, narrower, and straighter canal than femora of classes I and II/III or the normal control group. We suggest that when total hip replacement is performed in the patient with DDH, the femoral prosthesis should be chosen on the basis of the severity of the subluxation and the degree of anteversion of each individual femur.

The morphology of the femur in developmental dysplasia of the hip

PURPOSE Although CT scans are widely believed to provide the most accurate measurements of femoral anteversion, any estimate of the anteversion of the femur depends on the accuracy of the calculated axis of the femoral neck. We devised a method to measure the anteversion of the femur precisely using a 3D femoral computer model reconstructed from digitized femoral contours. Using this method, we compared the accuracy of three popular methods of anteversion measurement based on CT scans. METHOD The three popular CT methods were as follows: (a) the classic method of Weiner et al., based on a single CT image; (b) the method of Reikeras et al., in which the neck axis is defined by two superimposed images of the femoral head and neck; and (c) the method of Murphy et al., utilizing centroids of the head and the medullary canal. The accuracy of the single slice method was also examined using slices taken at four different neck slice levels within the proximal femur. CT scans of 30 femora were obtained using a helical CT scanner and reconstructed using custom software. RESULTS Based on the 3D model, the true anteversion of the femora averaged 19.8 +/- 9.3 degrees (SD). Using the method of Weiner et al., the anteversion of the femora was underestimated by an average of 6.4 degrees (predicted value 13.4 +/- 10.4 degrees). Conversely, Murphy et al.'s method overestimated anteversion by an average of 6.3 degrees with an average value of 26.0 +/- 9.1 degrees. The difference between the true anteversion and the values predicted by both of these methods was statistically significant (p < 0.001). The average anteversion measured according to the method of Reikeras et al. was 17.8 +/- 8.9 degrees, 2.0 degrees less than the true anteversion of the sample (p < 0.005). Anteversion angles predicted from a slice just below the inferior edge of the head averaged 18.3 +/- 9.5 degrees, only 1.5-3.1 degrees less than the true anteversion of the femur (p = 0.14). CONCLUSION The single slice CT method has sufficient accuracy for use, provided the slice is taken just below the femoral head. In cases with a femoral head deformity or a valgus neck or where difficulty is encountered in positioning the patient, 3D reconstruction appears essential for accurate measurement of anteversion.

A comparison of alternative methods of measuring femoral anteversion

The purpose of the current study was to evaluate whether safe acetabular component position depends on differences in pelvic location between the supine, standing, and sitting positions. The subjects of the current study were 101 patients who had total hip arthroplasty. Anteroposterior radiographs of the pelvis with the patients in the supine, standing, and sitting positions were obtained preoperatively and 1 year after total hip arthroplasty. Computed tomography images of the pelvis were obtained preoperatively. Using image matching between the three-dimensional computed tomography model and anteroposterior radiograph, pelvic flexion angles with the patient in the supine, standing, and sitting positions were calculated. The mean preoperative pelvic flexion angle was 5 degrees +/- 9 degrees (range, -37 degrees -30 degrees ) in the supine position, 3 degrees +/- 12 degrees (range, -46 degrees -33 degrees ) in the standing position, and -29 degrees +/- 12 degrees (range, -62 degrees -10 degrees ) in the sitting position. Because there was much intersubject variability in pelvic flexion angle, it is not appropriate to determine orientation of the acetabular component from anatomic landmarks. In 90% of the cases, the difference in pelvic flexion angle between the supine and standing positions preoperatively was 10 degrees or less. In 90% of the cases, there was 20 degrees or greater extension of the pelvis from the supine position to the sitting position preoperatively, and the safe range of flexion of the hip from anterior prosthetic impingement in the sitting position was 20 degrees or greater than that in the supine position. Preoperative pelvic position in each case was almost completely maintained 1 year after total hip arthroplasty. It is reasonable to regard the pelvic position in the supine position as the functional pelvic position and proper pelvic reference frame in determining optimal orientation of the acetabular component in 90% of cases before and 1 year after total hip arthroplasty, although an adjustment of orientation of the acetabular component was needed for the remaining cases.

Measurements of pelvic flexion angle using three-dimensional computed tomography.

“Zirconia Ceramics or `By Night, All Cats Are Grey.'”1 This was the curious title given four years ago to a French study regarding the controversy over zirconia in total hip replacement. The authors of that study commented: “In the absence of rigorous scientific clarification, information on biomaterials is frequently a source of confusion and misleading generalisations worrying to orthopaedic surgeons.”

Indeed, from their inception eighteen years ago, the performance of zirconia ceramic balls (Fig. 1) has been both confusing and controversial. Given the diversity of clinical results, it may well be true that not all zirconia balls were created equal. Thus, the above quotation appears as salient today as it was in 1999. A more recent French study reinforced this opinion: Hamadouche et al. noted that they could find only two studies that demonstrated favorable clinical results with the use of zirconia balls2. The literature published by major ceramic companies has also noted that certain clinical groups found higher rates of osteolysis with the zirconia-ultra-high molecular weight polyethylene couple3,4. How was this possible after an eighteen-year history of use of zirconia implants, with more than 400,000 zirconia implants reportedly sold worldwide5,6?



Fig. 1 
Retrieved ceramic balls at Loma Linda University Medical Center. From left to right: alumina, black zirconia, and white zirconia.



We must assume that the majority of implanted zirconia balls are performing very well today and that only a small percentage of patients have experienced some wear or other problems. However, it is imperative that we determine the mode and reason or reasons for the failures that have occurred. Thus, our collaborative goal was to determine the stability of zirconia balls following one to ten years of use in vivo and whether the reported variations in clinical results are …

Current status of zirconia used in total hip implants.

We investigated the effect of the Birmingham hip resurfacing (BHR) arthroplasty on the bone mineral density (BMD) of the femur. A comparative study was carried out on 26 hips in 25 patients. Group A consisted of 13 patients (13 hips) who had undergone resurfacing hip arthroplasty with the BHR system and group B of 12 patients (13 hips) who had had cementless total hip arthroplasty with a proximal circumferential plasma-spray titanium-coated anatomic Ti6A14V stem. Patients were matched for gender, state of disease and age at the time of surgery. The periprosthetic BMD of the femur was measured using dual-energy x-ray absorptiomentry of the Gruen zones at two years in patients in groups A and B. The median values of the BMD in zones 1 and 7 were 99% and 111%, respectively. The post-operative loss of the BMD in the proximal femur was significantly greater in group B than in group A. These findings show that the BHR system preserves the bone stock of the proximal femur after surgery.

Nobuhiko Sugano

Papers

The morphology of the femur in developmental dysplasia of the hip

A comparison of alternative methods of measuring femoral anteversion

Measurements of pelvic flexion angle using three-dimensional computed tomography.

Current status of zirconia used in total hip implants.

Preservation of the bone mineral density of the femur after surface replacement of the hip