Correction: A novel scaling methodology to reduce the biases associated with missing data from commercial activity monitors.

[This corrects the article DOI: 10.1371/journal.pone.0235144.].

A novel scaling methodology to reduce the biases associated with missing data from commercial activity monitors.

BACKGROUND: Commercial physical activity monitors have wide utility in the assessment of physical activity in research and clinical settings, however, the removal of devices results in missing data and has the potential to bias study conclusions. This study aimed to evaluate methods to address missingness in data collected from commercial activity monitors. METHODS: This study utilised 1526 days of near complete data from 109 adults participating in a European weight loss maintenance study (NoHoW). We conducted simulation experiments to test a novel scaling methodology (NoHoW method) and alternative imputation strategies (overall/individual mean imputation, overall/individual multiple imputation, Kalman imputation and random forest imputation). Methods were compared for hourly, daily and 14-day physical activity estimates for steps, total daily energy expenditure (TDEE) and time in physical activity categories. In a second simulation study, individual multiple imputation, Kalman imputation and the NoHoW method were tested at different positions and quantities of missingness. Equivalence testing and root mean squared error (RMSE) were used to evaluate the ability of each of the strategies relative to the true data. RESULTS: The NoHoW method, Kalman imputation and multiple imputation methods remained statistically equivalent (p<0.05) for all physical activity metrics at the 14-day level. In the second simulation study, RMSE tended to increase with increased missingness. Multiple imputation showed the smallest RMSE for Steps and TDEE at lower levels of missingness (<19%) and the Kalman and NoHoW methods were generally superior for imputing time in physical activity categories. CONCLUSION: Individual centred imputation approaches (NoHoW method, Kalman imputation and individual Multiple imputation) offer an effective means to reduce the biases associated with missing data from activity monitors and maximise data retention.

Stage-specific embryonic antigen-4 as a novel marker of ductal cells of human eccrine sweat glands.

BACKGROUND: Different populations of unipotent or multipotent stem cells have been identified in human epidermis and its appendages. It is well documented that these cells maintain tissue homeostasis and actively participate in epidermal regeneration after injury. However, there is no evidence of the presence of pluripotent stem cells in human epidermis. OBJECTIVES: In this study we investigated whether cells positive for embryonic stem cell marker stage-specific embryonic antigen-4 (SSEA-4) are present in adult human epidermis and, if so, whether they are pluripotent and correspond to the population of primitive stem cells. METHODS: The expressions of SSEA-4 and pluripotency transcription factors were analysed using flow cytometry. By means of immunohistochemical staining, we studied the exact localization of these cells in sections of human skin. RESULTS: We show that a population of SSEA-4+ cells is present in human epidermis. In contrast to the commonly accepted belief, the expression of SSEA-4 is not connected with the pluripotent character of isolated cells. We found that these SSEA-4+ cells are localized in the ducts of eccrine sweat glands. CONCLUSIONS: Our results indicate that SSEA-4 is a novel marker identifying the ductal cells of human sweat glands. The surface character of the antigen provides for a simple method of isolating this cell population and suggests applications of SSEA-4 for future cell therapy research.

Albumin gradients do not enrich Y-bearing human spermatozoa.

The aim of this study was to evaluate objectively whether or not discontinuous albumin gradients enrich the proportion of Y-bearing human sperm. A blinded, collaborative trial design was employed whereby a licensed centre prepared the sperm fractions using licensed procedures, coded the sperm slides and then sent them to an independent laboratory for determination of the X:Y ratio in each sperm fraction using X and Y chromosome-specific probes and double label fluorescence in-situ hybridization (FISH). The identification codes and FISH results were collated by an independent third observer. Two albumin gradient methods which are currently used by licensed centres for male sex pre-selection, protocol 3 and modified protocol 3, were tested. Essentially the same results were obtained for the two methods. Highly motile sperm fractions were recovered from the albumin gradients, and the recoveries of motile spermatozoa (1.3-8.5%) were within the optimal range reported to produce maximal enrichment of Y-bearing spermatozoa. FISH analysis, however, revealed no enrichment for Y-bearing spermatozoa with either method, and the overall X:Y ratios were not significantly different from 1.0. Some samples showed marginal enrichment of Y-bearing spermaotozoa, whereas others showed marginal enrichment of X-bearing spermaotozoa. In conclusion, this collaborative study has demonstrated that the protocol 3 and modified protocol 3 albumin gradient procedures do not enrich Y-bearing spermatozoa. The clinical use of albumin gradients for male sex preselection should be reconsidered in the light of this and other evidence.

Subcutaneous estradiol pellets for endometrial preparation in donor oocyte recipients with a poor endometrial response.

PURPOSE: The purpose of this study was to evaluate the clinical effectiveness of subcutaneous estradiol pellets in donor oocyte recipients with an inadequate endometrial response. METHODS: The subjects were 13 women with ovarian failure and a maximal endometrial thickness < 10 mm on standard estrogen regimens, as demonstrated during mock and/or prior oocyte donation cycles. They underwent pellet implantation (100-250 mg of estradiol) 6-13 weeks before oocyte donation. RESULTS: maximal (mean +/- SD) endometrial thickness was 8.7 +/- 1.5 mm on standard regimens, in contrast to 11.7 +/- 1.8 mm on pellets, while estradiol levels were 674 +/- 844 and 815 +/- 706 pg/ml, respectively. The estradiol:estrone ratio on pellets was > 1. There was 1 pregnancy with early loss during 10 cycles on other estrogen regimens and 12 pregnancies during 19 cycles on pellets. The pregnancy and implantation rates were, respectively, 63 and 27% on pellets and 41 and 14% on standard regimens in historical controls. CONCLUSIONS: We conclude that estradiol pellets after a single administration provide constant estradiol levels extending into the first trimester of pregnancy, a physiologic estradiol:estrone ratio, and a better endometrial response than standard estrogen regimens. Implantation and pregnancy rates are higher. This approach may be especially suitable for recipients with a poor endometrial response.

The effect of endometriosis, its stage and activity, and of autoantibodies on in vitro fertilization and embryo transfer success rates.

OBJECTIVES: To analyze IVF cycle parameters, including pregnancy rates (PR), in women with and without endometriosis and to evaluate the effect of the stage and activity of endometriosis and of autoantibodies. DESIGN: A retrospective analysis of 237 consecutive IVF cycles (193 patients), 119 in women with and 118 without endometriosis. The endometriosis group was further subdivided according to the stage and activity of the disease and autoantibody positivity. SETTING: Hospital-based and freestanding IVF programs with the same IVF team. PATIENTS: One hundred ninety-three women of reproductive age undergoing IVF; 84 had prior diagnosis of endometriosis, and 109 had other indications for IVF. Within the endometriosis group, 40 did and 44 did not have evidence of active disease. Autoantibodies were measured in 50 patients. INTERVENTIONS: The IVF protocol was standard with GnRH agonist administered from the midluteal phase of the preceding cycle. Variables included the method of ET and the use of corticosteroids. MAIN OUTCOME MEASURES: Number of follicles produced, number of eggs retrieved, fertilization rates, number of embryos transferred, and PR per transfer. RESULTS: There was no difference between groups in the response to stimulation, number of oocytes retrieved, number fertilized, and number cleaved. The overall PR was 27% per transfer; it was similar in women with and without endometriosis (29% and 25%, respectively). There was also no difference in PR according to the stage or activity of the disease. However, PR in autoantibody-positive and -negative patients were significantly different (22.9% and 45.7%, respectively). Among autoantibody-positive patients treated with corticosteroids, 8 of 10 conceived. CONCLUSIONS: This study confirms previous reports that IVF success rates are comparable in women with and without endometriosis regardless of the activity and stage of the disease. However, our study also indicates that autoantibodies may affect adversely implantation of embryos and that this effect can be overcome by administration of corticosteroids.