Reproductive history and osteoarthritis in the Women's Health Initiative.

Objective: To investigate the relationship between self-reported osteoarthritis (OA) and reproductive factors in the Women's Health Initiative (WHI). Method: We used multivariable logistic regression to study the association of self-reported OA and reproductive factors in the WHI Observational Study and Clinical Trial cohorts of 145 965 postmenopausal women, in a retrospective cross-sectional format. Results: In our cohort, we observed no clinically significant associations between reproductive factors and OA given small effect sizes. The following factors were associated with statistically significant increased likelihood of developing OA: younger age at menarche (p < 0.001), history of hysterectomy [adjusted odds ratio (aOR) 1.013, 95% confidence interval (CI) 1.004-1.022, p = 0.04 vs no hysterectomy], history of unilateral oophorectomy (aOR 1.015, 95% CI 1.004-1.026, p < 0.01 vs no oophorectomy), parity (aOR 1.017, 95% CI 1.009-1.026, p < 0.001), ever use of oral contraceptives (aOR 1.008, 95% CI 1.001-1.016, p < 0.01 vs never use), and current use of hormonal therapy (reference current users, aOR 0.951, 95% CI 0.943-0.959 for never users; aOR 0.981, 95% CI 0.972-0.989 for past users; global p < 0.001). Age at menopause, first birth, and pregnancy were not associated with OA. Among parous women, no clear pattern was observed with number of pregnancies, births, or duration of breastfeeding in relation to OA. Conclusion: Our study showed that reproductive factors did not have significant clinical associations with OA after controlling for confounders. This may be due to complex hormonal effects. Additional investigation is warranted in prospective cohort studies. The Women's Health Initiative is registered under ClinicalTrials.gov. Trial registration ID: NCT00000611.

Virtually there: An innovative approach for training oncology pharmacy residents in gynecologic oncology.

OBJECTIVE: To develop an alternative approach to provide oncology pharmacy practice residents' education and training in the management of gynecologic malignancies in the absence of a specialist in this area at their institution. SETTING: Gynecologic oncology is a unique specialty in oncology. There is a need for more oncology clinical pharmacy specialists to participate in the care of patients with gynecologic malignancies as many do not have specific education in this area. PRACTICE DESCRIPTION: A virtual learning experience was developed that included all aspects of a typical experience with the exception of direct patient care. Postgraduate year 2 oncology pharmacy residents from 3 different programs were included. PRACTICE INNOVATION: Although the number of oncology clinical pharmacy specialists who are subspecialized in gynecologic oncology has grown, it is difficult to find experienced preceptors in gynecology oncology. We set to offer a virtual learning environment for programs that did not have a dedicated or highly specialized pharmacist in this area. EVALUATION: A pre- and postlearning assessment of the resident's knowledge of gynecologic malignancies was administered. Each trainee independently completed a validated 20-question gynecologic oncology knowledge assessment tool before and again after completion of all sessions. Midpoint and end-of-experience evaluations were completed via the phone with each resident. All evaluations were documented in PharmAcademic (McCreadie Group, Ann Arbor, MI), a required software program for postgraduate residency training programs. RESULTS: To date, 7 oncology pharmacy practice residents completed the virtual experience. A 42% improvement in scores pertaining to gynecologic oncology knowledge was identified. Residents were also satisfied with the overall virtual experience. Based on the assessment tool, all the residents gave positive evaluations with "always true" for 6 of the 7 questions. CONCLUSIONS: This pilot of a virtual experience was a successful platform to provide clinical knowledge and skills for oncology pharmacy residents in gynecologic oncology.

TAPP or TEP for Recurrent Inguinal Hernia? Population-Based Analysis of Prospective Data on 1309 Patients Undergoing Endoscopic Repair for Recurrent Inguinal Hernia.

BACKGROUND: Whether total extraperitoneal inguinal hernia repair (TEP) is associated with worse outcomes compared to transabdominal preperitoneal inguinal hernia repair (TAPP) for the treatment of recurrent inguinal hernia continues to be a matter of debate. The objective of this large cohort study is to compare complications, conversion rates and postoperative length of hospital stay between patients undergoing TEP or TAPP for unilateral recurrent inguinal hernia repair. METHOD: Based on prospective data of the Swiss Association of Laparoscopic and Thoracoscopic Surgery, all patients who underwent elective TEP or TAPP for unilateral recurrent inguinal hernia between 1995 and 2006 were included. The following outcomes were compared: conversion rates, intraoperative complications, surgical postoperative complications and duration of operation. RESULTS: Data on 1309 patients undergoing TEP (n = 1022) and TAPP (n = 287) for recurrent inguinal hernia were prospectively collected. Average age, BMI and ASA score were similar in both groups. Patients undergoing TEP had a significantly increased rate of intraoperative complications (TEP 6.3 % vs. TAPP 2.8 %, p = 0.0225). Duration of operation was longer for patients undergoing TEP (TEP 80.3 vs. TAPP 73.0 min, p < 0.0023) while postoperative length of hospital stay was longer for patients undergoing TAPP (TEP 2.6 vs. TAPP 3.1 day, p = 0.0145). Surgical postoperative complications (TEP 3.52 % vs. TAPP 2.09 %, p = 0.2239), general postoperative complications (TEP 1.47 % vs. TAPP 0.7 %, p = 0.3081) and conversion rates (TEP 2.15 % vs. TAPP 1.39 %, p = 0.4155) were not significantly different. CONCLUSION: This study is the first population-based analysis comparing outcomes of patients with recurrent inguinal hernia undergoing TEP versus TAPP in a prospective cohort of over 1300 patients. Intraoperative complications were significantly higher in patients undergoing TEP. The TEP technique was associated with longer operating times, but a shorter postoperative length of hospital stay. Nonetheless, the absolute outcome differences are small and thus, on a population-based level, both techniques appear to be safe and effective for patients undergoing endoscopic repair for unilateral recurrent inguinal hernia.

Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women's Sexual Health and The North American Menopause Society.

BACKGROUND: In 2012, the Board of Directors of the International Society for the Study of Women's Sexual Health (ISSWSH) and the Board of Trustees of The North American Menopause Society (NAMS) acknowledged the need to review current terminology associated with genitourinary tract symptoms related to menopause. METHODS: The two societies cosponsored a terminology consensus conference, which was held in May 2013. RESULTS AND CONCLUSION: Members of the consensus conference agreed that the term genitourinary syndrome of menopause (GSM) is a medically more accurate, all-encompassing, and publicly acceptable term than vulvovaginal atrophy. GSM is defined as a collection of symptoms and signs associated with a decrease in estrogen and other sex steroids involving changes to the labia majora/minora, clitoris, vestibule/introitus, vagina, urethra and bladder. The syndrome may include but is not limited to genital symptoms of dryness, burning, and irritation; sexual symptoms of lack of lubrication, discomfort or pain, and impaired function; and urinary symptoms of urgency, dysuria and recurrent urinary tract infections. Women may present with some or all of the signs and symptoms, which must be bothersome and should not be better accounted for by another diagnosis. The term was presented and discussed at the annual meeting of each society. The respective Boards of NAMS and ISSWSH formally endorsed the new terminology - genitourinary syndrome of menopause (GSM) - in 2014.

Ion implantation of graphene-toward IC compatible technologies.

Doping of graphene via low energy ion implantation could open possibilities for fabrication of nanometer-scale patterned graphene-based devices as well as for graphene functionalization compatible with large-scale integrated semiconductor technology. Using advanced electron microscopy/spectroscopy methods, we show for the first time directly that graphene can be doped with B and N via ion implantation and that the retention is in good agreement with predictions from calculation-based literature values. Atomic resolution high-angle dark field imaging (HAADF) combined with single-atom electron energy loss (EEL) spectroscopy reveals that for sufficiently low implantation energies ions are predominantly substitutionally incorporated into the graphene lattice with a very small fraction residing in defect-related sites.

Global consensus statement on menopausal hormone therapy.

The following Consensus Statement is endorsed by The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society.

Metabolic surgery-principles and current concepts.

INTRODUCTION: In the almost six decades of bariatric surgery, a variety of surgical approaches to treating morbid obesity have been developed. HISTORY AND EVOLUTION: Rather than prior techniques being continually superseded by new ones, a broad choice of surgical solutions based on restrictive, malabsorptive, humoral effects, or combinations thereof, is now available. In fact, in recent years, the advent of surgically modifying human metabolism promises new approaches to ameliorate traditionally medically treated metabolic entities, i.e., diabetes, even in the non-obese. The understanding of the various metabolic effects have led to a paradigm shift from bariatric surgery as a solely weight-reducing procedure to metabolic surgery affecting whole body metabolism. CONCLUSION: The bariatric surgeon now faces the challenge and opportunity of selecting the most suitable technique for each individual case. To assist in such decision-making, this review, Metabolic surgery-principles and current concepts, is presented, tracing the historical development; describing the various surgical techniques; elucidating the mechanisms by which glycemic control can be achieved that involve favorable changes in insulin secretion and insulin sensitivity, gut hormones, adipokines, energy expenditure, appetite, and preference for low glycemic index foods; as well as exploring the fascinating future potential of this new interdisciplinary field.

Blocking of indium incorporation by antimony in III-V-Sb nanostructures.

The addition of antimony to III-V nanostructures is expected to give greater freedom in bandgap engineering for device applications. One of the main challenges to overcome is the effect of indium and antimony surface segregation. Using several very high resolution analysis techniques we clearly demonstrate blocking of indium incorporation by antimony. Furthermore, indium incorporation resumes when the antimony concentration drops below a critical level. This leads to major differences between nominal and actual structures.

Magnetic films on nanoperforated templates: a route towards percolated perpendicular media.

We present a study on the magnetization reversal in Co/Pt multilayer films with an out-of-plane easy axis of magnetization deposited onto substrates with densely distributed perforations with an average period as small as 34 nm. Deposition of magnetic Co/Pt multilayers onto the nanoperforated surface results in an array of magnetic nanodots surrounded by a continuous magnetic film. Following the evolution of the magnetic domain pattern in the system, we suggest that domain walls are pinned on structural inhomogeneities given by the underlying nanoperforated template. Furthermore, a series of micromagnetic simulations was performed in order to understand the modification of the pinning strength of domain walls due to the magnetic interaction between nanodots and the surrounding film. The results of the simulations show that magnetic exchange coupling between the nanodots and the surrounding film strongly influences the pinning behavior of the magnetic domain walls which can be optimized to provide maximal pinning.

Catheter ablation in ASymptomatic PEDiatric patients with ventricular preexcitation: results from the multicenter "CASPED" study.

BACKGROUND: As there are limited data about the clinical practice of catheter ablation in asymptomatic children and adolescents with ventricular preexcitation on ECG, we performed the multicenter "CASPED" (Catheter ablation in ASymptomatic PEDiatric patients with Ventricular Preexcitation) study. METHODS AND RESULTS: In 182 consecutive children and adolescents aged between 8 and 18 years (mean age 12.9 ± 2.6 years; 65% male) with asymptomatic ventricular preexcitation, a total of 196 accessory pathways (APs) were targeted. APs were right sided (62%) or left sided (38%). The most common right-sided AP location was the posteroseptal region (38%). Ablation was performed using radiofrequency (RF) energy (93%), cryoablation (4%) or both (3%). Mean procedure time was 137.6 ± 62.0 min with a mean fluoroscopy time of 15.6 ± 13.8 min. A 3D mapping or catheter localization system was used in 32% of patients. Catheter ablation was acutely successful in 166/182 patients (91.2%). Mortality was 0% and there were no major periprocedural complications. AP recurrence was observed in 14/166 patients (8.4%) during a mean follow-up time of 19.7 ± 8.5 months. A second ablation attempt was performed in 20 patients and was successful in 16/20 patients (80%). Overall, long-term success rate was 92.3%. CONCLUSION: In this retrospective multicenter study, the outcome of catheter ablation for asymptomatic preexcitation in children and adolescents irrespective of antegrade AP conduction properties is summarized. The complication rate was low and success rate was high, the latter mainly depending on pathway location. The promising results of the study may have future impact on the ongoing risk-benefit discussion regarding catheter ablation in the setting of asymptomatic preexcitation in children and adolescents.

Calibration to American options: numerical investigation of the de-Americanization method.

American options are the reference instruments for the model calibration of a large and important class of single stocks. For this task, a fast and accurate pricing algorithm is indispensable. The literature mainly discusses pricing methods for American options that are based on Monte Carlo, tree and partial differential equation methods. We present an alternative approach that has become popular under the name de-Americanization in the financial industry. The method is easy to implement and enjoys fast run-times (compared to a direct calibration to American options). Since it is based on ad hoc simplifications, however, theoretical results guaranteeing reliability are not available. To quantify the resulting methodological risk, we empirically test the performance of the de-Americanization method for calibration. We classify the scenarios in which de-Americanization performs very well. However, we also identify the cases where de-Americanization oversimplifies and can result in large errors.

[Prediction of respiratory complications after radical surgeries for non-small cell carcinoma of the lung].

A predictive role of volume-velocity (VV) indices of ventilation in prognosis of respiratory complications after radical surgeries for non-small cell carcinoma of the lung was evaluated. It is demonstrated that decreased VV indices of ventilation before surgery directly correlate with a respiratory complication rate after surgery. New methods of diagnosis of ventilation disorders and of monitoring are regarded as promising.

[Short-term results of radical surgeries for non-small cell cancer of the lung].

The results of radical surgical treatment of 358 patients with NSCCL were analyzed. Majority of patients were men (84.6%) and persons older 60 years -- 239 (66.8%) patients. Central cancer was diagnosed in 164 (45,8%) patients, peripheral -- in 194 (54.2%). There were 137 (38.3%) pneumonectomies, 184 (51.4%) lobectomies; 149 (41.6%) surgeries were combined. Complications after radical surgeries were seen in 92 (25.7%) of 358 patients, including 18 (5.0%) patients with <> complications and 74 (21%) patients with <> ones. Complications were seen more often in patients over 60 years and occurred less frequently after segmentectomy (7 patients). Lethality was 5.0% (18 patients). Respiratory complications (7 cases) and pulmonary embolism (5 patients) were the main causes of lethal outcome.

CD34+ selected bone marrow grafts are radioprotective and establish mixed chimerism in dogs given high dose total body irradiation.

BACKGROUND: Canine stem cell transplantation models have provided important preclinical information for human clinical studies. The recent cloning of cDNA for canine CD34 and the production of monoclonal antibodies that recognize canine CD34 have been the basis for the development of techniques for the large-scale enrichment of canine hematopoietic progenitor cells. In this study, we evaluated the in vivo functional properties of canine bone marrow CD34+ cells after a myeloablative conditioning regimen. METHODS: After 920 cGy total body irradiation, three dogs received infusion of autologous CD34+ selected cells from the marrow, three dogs CD34+ depleted autologous marrow cells, and two dogs received CD34+ autologous marrow cells that were immunomagnetically selected and then further purified by cell sorting. In addition, four dogs received allogeneic marrow enriched for CD34+ cells from dog leukocyte antigen-identical littermates to investigate long-term repopulating function of CD34+ cells. Chimerism studies were performed using polymerase chain reaction to detect highly polymorphic microsatellite markers. RESULTS: In three recipients of autologous marrow enriched for CD34+ cells to between 29% and 70% (1.6 x 10(6) to 3.4x10(6) CD34+ cells/kg), prompt and full hematopoietic recovery occurred, whereas in three dogs that received marrow depleted of CD34+ cells (1 x 10(7) cells/kg), no hematopoietic recovery was achieved. In two dogs that received highly purified CD34+ cells (purity: 98% and 96%, 0.79x10(6) to 0.547x 10(6) CD34+ cells/kg), delayed but full hematopoietic recovery was seen. Three of four allograft recipients of 1.75x10(6) to 6.8x10(6) CD34+ cells/kg engrafted and showed full hematopoietic recovery, whereas one dog rejected the graft. The three long-term survivors showed stable mixed hematopoietic chimerism with predominantly donor hematopoiesis. CONCLUSION: Transplantation of canine CD34+ cells after lethal total body irradiation provides radioprotection and gives rise to long-term hematopoietic reconstitution. Stable donor/host mixed chimerism was observed in allograft recipients most likely as a result of T-cell depletion of the grafts. Our findings suggest a future role for canine preclinical transplant studies involving in vitro manipulation of hematopoietic pro.

Ex vivo expansion of canine dendritic cells from CD34+ bone marrow progenitor cells.

BACKGROUND: The aims of this study were to ex vivo expand canine dendritic cells and determine their phenotype and functional characteristics. METHODS: CD34+-selected cells and CD34+-depleted canine bone marrow (BM) cells were cultured in Iscove's modified medium for 14 days. Cytokines added to the cultures included human granylocyte/macrophage colony-stimulating factor 5 ng/ml, hFlt3 ligand 200 ng/ml, and human tumor necrosis factor-alpha 10 ng/ml. Cultured cells and purified subpopulations were assessed for cell surface antigen expression, morphology, and function by flow cytometric analysis, electron microscopy, and an allogeneic mixed lymphocyte reaction at day 14. RESULTS: Two main cell populations were identified, DR++(bright)/CD14- and DR+(dim)/CD14+. Ex vivo expanded CD34+-selected cells showed increased allostimulatory activity compared to both cultured CD34+-depleted cells and mononuclear cells. In contrast, ex vivo expansion from CD34+-depleted cells was unsuccessful. After sorting cells from the ex vivo expanded CD34+-selected bone marrow to enrich for DR++/CD14- cells, a 42-fold increase (median) of allostimulatory activity was observed as compared with sorted DR+/CD14+ cells (P=0.02). CONCLUSIONS: Cells with dentric cell-like phenotypes and functions can be cultured from canine CD34+-selected bone marrow cells. Future studies will address the roles of these cells in engraftment, graft versus host reactions and graft-host tolerance in a canine hematogoietic stem cell transplantaton model.

FLT3 ligand promotes engraftment of allogeneic hematopoietic stem cells without significant graft-versus-host disease.

BACKGROUND: Graft-versus-host (GVH) reactions contribute to stable engraftment of allogeneic hematopoietic stem cell transplants. It was hypothesized that the in vivo expansion of recipient dendritic cells (DC) with the administration of ligand for Flt3 (FL) could promote allogeneic engraftment after reduced-intensity conditioning by enhancing the GVH effect. METHODS: FL was first administered to three nonirradiated healthy dogs for 13 days at a dosage of 100 microg/kg/day. Next, nine dogs received 4.5 Gy total-body irradiation (TBI) and unmodified marrow grafts from dog leukocyte antigen (DLA)-identical littermates without posttransplant immunosuppression. FL was administered to the recipients at a dosage of 100 microg/kg/day from day -7 until day +5. RESULTS: In normal dogs, FL produced significant increases in monocytes (CD14+) and neutrophils in the peripheral blood, a marked increase in CD1c+ cells with DC-type morphology in lymph nodes, and increased alloreactivity of third-party responders to peripheral blood mononuclear cells in mixed lymphocyte reactions (P<0.001). Sustained engraftment was observed in eight of nine (89%) FL-treated dogs compared with 14 of 37 (38%) controls (P=0.02, logistic regression). All engrafted FL-treated dogs became stable complete (n=2) or mixed (n=6) hematopoietic chimeras without significant graft-versus-host disease (GVHD). Recipient chimeric dogs (n=4) were tolerant to skin transplants from their marrow donors but rejected skin grafts from unrelated dogs within 7 to 9 days (median, 8 days). CONCLUSIONS: In this study, the authors showed that FL administered to recipients promotes stable engraftment of allogeneic marrow from DLA-identical littermates after 4.5 Gy TBI without significant GVHD.

NOD/SCID mice transplanted with marrow from patients with myelodysplastic syndrome (MDS) show long-term propagation of normal but not clonal human precursors.

Sublethally irradiated NOD/SCID mice were transplanted with hematopoietic progenitor cells obtained from the marrow of patients with myelodysplastic syndromes (MDS). Engraftment of MDS cells, as determined by flow cytometry, was delayed compared to marrow from normal donors. Human CD38(+)CD34(-) cells were prominent in marrows and spleens of MDS chimeras. CD34(+)CD38(-), CD34(+)CD38(+) and T cells were also easily detected. Human myeloid cells (CD33(+); CD15(+)) were present in low proportions. No clonal precursors were identified by fluorescent in situ hybridization (FISH) or by molecular analysis of polymorphic X-linked markers in mice with documented engraftment of human cells more than 2 months after transplantation. These data indicate that human cells present in murine MDS chimeras, at the levels of sensitivity of our assays, were derived from residual normal cells in human MDS marrow, and suggest that the NOD/SCID environment was not conducive to the expansion of clonal MDS precursors. This model may allow identification of factors relevant for sustaining or expanding clonal precursors.

Elemental mapping using the Ga 3d and In 4d transitions in the epsilon2 absorption spectra derived from EELS.

It is proposed that by using the valence-band states in electron energy loss spectroscopy, high-spatial resolution maps of quantitative elemental composition may be acquired with high acquisition rates. Further, it is shown that by using the epsilon(2) spectrum instead of single scattering data, the noise in the observed transitions and associated maps is significantly reduced. The epsilon(2) spectra are derived through a Kramers-Kronig transformation from electron energy loss spectra obtained in a scanning transmission electron microscope. Using transitions that occur in the epsilon(2) absorption spectrum (<40eV), quantitative elemental maps for III-V device structures have been produced. An example is provided using the Ga 3d transition to map a GaInNAs/GaAs laser structure. Weaker transitions such as In 4d have also been used to verify the Ga elemental distribution.

Hormone replacement for the new millennium.

The field of hormone replacement therapy continues to evolve. Guidelines and dosing regimens change in response to new data and treatment options. It is important for the clinician to remain informed to be able to interpret new findings for the patient.

Multiple therapies for vaginal bleeding secondary to large uterine myomas.

Acute vaginal bleeding secondary to uterine myomas can be a devastating event. We report the use of a combined therapeutic approach in a patient who presented with protracted bleeding of a myomatous uterus that was equivalent in size to a 38 week gestation. This patient's course was further complicated by her refusal of blood or blood products.