Impact of gonadotropin type on progesterone elevation during ovarian stimulation in GnRH antagonist cycles.

STUDY QUESTION: Does hormonal stimulation with corifollitropin alpha (CFA) only, mimicking a step down protocol, result in lower incidence of progesterone elevation on the day of hCGtrigger as compared to sustained stimulation with recombinant FSH (rFSH)? SUMMARY ANSWER: The current findings support the concept that sustained FSH stimulus contributes to premature progesterone elevation in stimulated IVF cycles. WHAT IS KNOWN ALREADY: Serum progesterone rise during the follicular phase of ovarian stimulation for IVF treatment seems to be related to a poorer reproductive outcome. However, the mechanism by which the rise in progesterone is caused is not yet fully understood. STUDY DESIGN, SIZE, DURATION: This study was a post hoc analysis of data from two multi-center, randomized, double-blind, double-dummy, active-controlled, non-inferiority trials, ENGAGE and PURSUE, conducted from June 2006 to January 2008 and from July 2010 to October 2012 respectively. PARTICIPANTS/MATERIALS, SETTING, METHODS: In the ENGAGE-study, 1506 women, aged 18-36 years, were allocated to either a single injection of 150 mg CFA or daily injections of 200 IU rFSH in the first week of stimulation, using a standard GnRH antagonist protocol. In the PURSUE-study, a total of 1390 women, aged 35-42 years, were allocated to either a single injection of 150 mg of CFA or daily 300 IU of rFSH for the first week, again using a standard GnRH antagonist protocol. In both trials, daily rFSH was continued until three follicles reached >17 mm in size. All women had a body weight of between 50 and 90 kg, regular menstrual cycles and an indication for ovarian stimulation before IVF. The incidence of progesterone elevation on day of hCG-trigger in patients with CFA only or rFSH stimulation, and triggered on Day 8 of stimulation, was analyzed. MAIN RESULTS AND THE ROLE OF CHANCE: Of patients with CFA only stimulation, 5.4% (13/239 patients) showed a progesterone elevation above 1.5 ng/ml on day of hCG-trigger, whereas patients with rFSH stimulation had a significant higher incidence of progesterone elevation (18.3%; 62/339 patients) (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: Post hoc analysis of data from previously published trials could be considered as a reason for caution. WIDER IMPLICATIONS OF THE FINDINGS: Future studies should evaluate whether it would be possible to prevent a premature progesterone rise in cycles stimulated with daily FSH by using a step down protocol towards the end of the follicular phase. STUDY FUNDING/COMPETING INTERESTS: Financial/Material Support was provided by Merck & Co., Inc., Kenilworth, NJ, USA. Davis Gates is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and may own stock and/or hold stock options in the company. Fabiola Beligotti is an employee of MSD, Italy, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and may own stock and/or hold stock options in the company. Barbara Lawrenz, Nils Engelmann and Human M. Fatemi have no conflict of interest. TRIAL REGISTRATION NUMBER: ENGAGE study: ClinicalTrials.gov identifier NTC00696800. PURSUE-study: NCT01144416.

Formation and stability of impurity "snakes" in tokamak plasmas.

New observations of the formation and dynamics of long-lived impurity-induced helical "snake" modes in tokamak plasmas have recently been carried out on Alcator C-Mod. The snakes form as an asymmetry in the impurity ion density that undergoes a seamless transition from a small helically displaced density to a large crescent-shaped helical structure inside q<1, with a regularly sawtoothing core. The observations show that the conditions for the formation and persistence of a snake cannot be explained by plasma pressure alone. Instead, many features arise naturally from nonlinear interactions in a 3D MHD model that separately evolves the plasma density and temperature.

Origin of tokamak density limit scalings.

The onset criterion for radiation driven islands [P. H. Rebut and M. Hugon, Plasma Physics and Controlled Nuclear Fusion Research 1984: Proc. 10th Int. Conf. London, 1984, (IAEA, Vienna, 1985), Vol. 2] in combination with a simple cylindrical model of tokamak current channel behavior is consistent with the empirical scaling of the tokamak density limit [M. Greenwald, Nucl. Fusion 28, 2199 (1988)]. Many other unexplained phenomena at the density limit are consistent with this novel physics mechanism.

Initial operation and data processing on a system for real-time evaluation of Thomson scattering signals on the Large Helical Device.

A scalable system for real-time analysis of electron temperature and density based on signals from the Thomson scattering diagnostic, initially developed for and installed on the NSTX-U experiment, was recently adapted for the Large Helical Device and operated for the first time during plasma discharges. During its initial operation run, it routinely recorded and processed signals for four spatial points at the laser repetition rate of 30 Hz, well within the system's rated capability for 60 Hz. We present examples of data collected from this initial run and describe subsequent adaptations to the analysis code to improve the fidelity of the temperature calculations.

Surgically Implanted Electrodes Enable Real-Time Finger and Grasp Pattern Recognition for Prosthetic Hands.

Currently available prosthetic hands are capable of actuating anywhere from five to 30 degrees of freedom (DOF). However, grasp control of these devices remains unintuitive and cumbersome. To address this issue, we propose directly extracting finger commands from the neuromuscular system via electrodes implanted in residual innervated muscles and regenerative peripheral nerve interfaces (RPNIs). Two persons with transradial amputations had RPNIs created by suturing autologous free muscle grafts to their transected median, ulnar, and dorsal radial sensory nerves. Bipolar electrodes were surgically implanted into their ulnar and median RPNIs and into their residual innervated muscles. The implanted electrodes recorded local electromyography (EMG) with Signal-to-Noise Ratios ranging from 23 to 350 measured across various movements. In a series of single-day experiments, participants used a high speed pattern recognition system to control a virtual prosthetic hand in real-time. Both participants were able to transition between 10 pseudo-randomly cued individual finger and wrist postures in the virtual environment with an average online accuracy of 86.5% and latency of 255 ms. When the set was reduced to five grasp postures, average metrics improved to 97.9% online accuracy and 135 ms latency. Virtual task performance remained stable across untrained static arm positions while supporting the weight of the prosthesis. Participants also used the high speed classifier to switch between robotic prosthetic grips and complete a functional performance assessment. These results demonstrate that pattern recognition systems can use the high-quality EMG afforded by intramuscular electrodes and RPNIs to provide users with fast and accurate grasp control. SUMMARY: Surgically implanted electrodes recorded finger-specific electromyography enabling reliable finger and grasp control of an upper limb prosthesis.

Distribution of active gene sequences: a subset associated with tightly bound chromosomal proteins.

The distribution of active polyadenylate-messenger RNA sequences in fractionated chicken liver chromatin was examined. A portion of these active gene sequences is concentrated in a DNA fraction retained by tightly bound nonhistone chromosomal proteins, while the nonretained DNA fraction is substantially depleted of a portion of these sequences. These findings suggest that the tightly bound nonhistones are physically associated with a subset of active gene sequences.

Leaf temperatures of desert plants.

Temperatures of small leaves of many desert plants are within 3 degrees C of air temperature in contrast to the temperature of Opuntia in the same locale; this plant has a temperature 10 degrees to 16 degrees C above air temperature. Theoretical4 justification for the observation is given based on an energy budget analysis.

Simultaneous feedback control of plasma rotation and stored energy on NSTX-U using neoclassical toroidal viscosity and neutral beam injection.

A model-based feedback system is presented enabling the simultaneous control of the stored energy through ßn and the toroidal rotation profile of the plasma in National Spherical Torus eXperiment Upgrade device. Actuation is obtained using the momentum from six injected neutral beams and the neoclassical toroidal viscosity generated by applying three-dimensional magnetic fields. Based on a model of the momentum diffusion and torque balance, a feedback controller is designed and tested in closed-loop simulations using TRANSP, a time dependent transport analysis code, in predictive mode. Promising results for the ongoing experimental implementation of controllers are obtained.

Risk factors for disability among U.S. adults with arthritis.

This article studies risk factors for physical and social disability among U.S. adults ages 55+ who have arthritis, compared to non-arthritis persons of those ages. The dependent variables refer to difficulties in walking, physical functioning (motions and strength), personal care, and household care. The data set is the Supplement on Aging (SOA) (n = 16,148) that accompanied the 1984 National Health Interview Survey. The SOA data are cross-sectional; relationships of risk factors to disability suggest causation but do not directly demonstrate it. Logistic regressions show that risk factors are similar for arthritis and non-arthritis people, with one important exception. (1) The similarities are: For both groups, odds of disability rise with age, diminish with education, and are higher for non-whites and non-married persons. Disability rises with number of chronic diseases and impairments, and it is elevated for underweight persons (Body Mass Index (BMI) less than 20; further analysis indicates this reflects incomplete control of their severe illness status). Long duration of arthritis and recent medical care for it are associated with disability. (2) The exception is: Severe overweight (BMI greater than or equal to 30) is a disability risk factor for arthritis people, but not for non-arthritis people. Previous research has shown that obesity/overweight is a risk factor for etiology of osteoarthritis; our analysis now shows its continued importance for disability when the disease is present.

Loratadine versus cetirizine: assessment of somnolence and motivation during the workday.

OBJECTIVE: This parallel-group, double-blind study compared the somnolence and motivation profiles of 2 second-generation antihistamines, loratadine and cetirizine, in patients with allergic rhinitis. BACKGROUND: Second-generation antihistamines were developed to provide symptomatic relief from allergic disorders without the unwanted side effects of first-generation antihistamines, including somnolence. Recent research has indicated that not all second-generation antihistamines are comparable with respect to somnolence and other cognitive processes. METHODS: Patients aged > or = 12 years and actively exhibiting symptoms of allergic rhinitis were randomized to 2 treatment groups to receive 10 mg loratadine or 10 mg cetirizine daily at 8:00 AM for 1 week. After patients took the medication, their somnolence and degree of motivation to perform activities were recorded in an electronic diary using a visual analog scale 4 times during the workday (8:00 AM, 10:00 AM, noon, and 3:00 PM). RESULTS: Sixty patients (31 men, 29 women) were randomized to treatment. Somnolence scores were similar for both groups at baseline and at the time of dosing (8:00 AM). However, there was a statistically significant difference in somnolence scores between the loratadine and cetirizine groups at 10:00 AM (P = 0.008), noon (P = 0.001), and 3:00 PM (P < 0.001), with the cetirizine group showing a greater degree of somnolence. The scores on motivation to perform activities were similar for both groups at the baseline and 8:00-AM measurements. In parallel with the somnolence scores, there were statistically significant differences in motivation scores between the loratadine and cetirizine groups at 10:00 AM (P = 0.014), noon (P = 0.001), and 3:00 PM (P < 0.001), indicating that patients taking loratadine were relatively more motivated during the workday. CONCLUSION: The results of this study demonstrate that in patients aged > or = 12 years who had allergic rhinitis, cetirizine use promoted somnolence and decreased motivation to perform activities during the workday compared with loratadine.

Two randomized controlled trials comparing the tubal ring and filshie clip for tubal sterilization.

OBJECTIVE: To compare the effectiveness and safety of the Filshie Clip and Tubal Ring systems when applied via minilaparotomy and laparoscopy. DESIGN: Prospective, multicenter randomized controlled clinical trial, with postoperative evaluation by a physician who was masked to the operative technique. SETTING: Healthy volunteers in a variety of hospital settings. PATIENT(S): 2746 women (915 in the minilaparotomy study and 1831 in the laparoscopy study) who had requested permanent surgical sterilization. INTERVENTION(S): Surgical tubal ligation, using either Filshie Clips or Tubal Rings. A physician other than the surgeon evaluated the patients after the operation and again at 1, 6, and 12 months after surgery. MAIN OUTCOME MEASURE(S): Pregnancy rates and safety-related events. RESULT(S): During the 12 months after surgery, two women who received the Filshie Clip and two women who received the Tubal Ring became pregnant, giving a 12-month life-table pregnancy probability of 1.7 per 1000 women in both groups. The Tubal Ring was more difficult to apply and had higher rates of tubal or mesosalpingeal injuries at surgery. The Filshie Clip group had three cases of spontaneous clip expulsion during the follow-up period. CONCLUSION(S): Both the Filshie Clip and Tubal Ring are effective and safe for use in tubal occlusion.

Performing tubal sterilizations during women's postpartum hospitalization: a review of the United States and international experiences.

A considerable number of tubal sterilizations have been performed while women are still in hospital after delivery in the United States as well as in other countries. There are few review papers exclusively on this sterilization modality. This paper provides a comprehensive review of results reported from recent studies of this approach, and answers the pertinent medical and related questions such as: To achieve maximum safety, what is the best time to perform the procedure during the women's postpartum hospitalization? Specifically, is it advisable for the procedure to be performed while the woman is still on the delivery table? What surgical approach and tubal occlusion technique are preferred? What are the risks that the women undergoing sterilization immediately or soon after delivery may incur the short- and long-term medical sequelae, and to conceive accidental pregnancy? What effect does sterilization have on lactation? And how should the women be screened and counseled to prevent poststerilization regret, generally thought to be more likely to occur in women after postpartum sterilization? Newly-developed mechanical tubal occlusion techniques have been included for consideration. Practical guidelines are given in this paper to help service providers achieve maximum safety and satisfaction for their patients with this convenient and low-cost method of postpartum sterilization.

PIP: Postpartum tubal sterilization (PPTS), referring to sterilization before day 42, usually within 48 hours, and often immediate sterilization while the woman is still on the delivery table, is reviewed from reports from developed and developing countries. PPTS is convenient and cost-effective both for the woman and for the provider. Factors arguing for greater safety of PPTS are the natural hemostatic and anti-infective state of the puerperium, umbilical location of the fundus, use of the same anesthesia, and same operative site in case of cesarean delivery. Some have argued that the adnexa are more vascular and enlarged at this time. Yet PPTS done up to 7 days after delivery does not bear any increased burden of complications, surgical drawbacks, or complaints than interval sterilization. Minilaparotomy is recommended over laparoscopic sterilization, unless the surgeon is extremely experienced, since laparoscopy at this time is risky and difficult. The Pomeroy method is most often used, the Irving method is most reliable, while tubal clips may offer an improved chance of reversal. Anesthetic deaths are rarely reported from developed countries with PPTS. Developing countries usually use local anesthesia, and have fewer obese women and fewer anesthesia-related complications. Somewhat higher pregnancy rates have been reported with PPTS, although small case series, and non-random selection of cases may flaw this interpretation. There has been more PPTS sterilization regret after cesarean deliveries than after vaginal deliveries. It is important to counsel women, especially those at risk of regret, who are young, of low parity, or at risk of life changes, that sterilization is irreversible. Only patients with no labor and delivery complications and with a health infant should be considered candidates for PPTS.

Development of a photosynthesis model with an emphasis on ecological applications : V. Test of the applicability of a steady-state model to description of net photosynthesis of Prunus armeniaca under field conditions.

A physiologically based steady-state model of whole leaf photosynthesis (WHOLEPHOT) is used to describe net photosynthesis daily time courses in Prunus armeniaca. Net photosynthesis rates are calculated in response to incident light intensity, leaf temperature, air carbon dioxide concentration, and leaf diffusion resistance measured at five minute intervals. The steady-state calculations closely approximate the observed net photosynthesis rates for a broad range of weather conditions and leaf stomatal behavior.

Development of a photosynthesis model with an emphasis on ecological applications : I. Theory.

In this paper, a description of photosynthesis in a single leaf is developed that separates physiological sub-processes and that is practical to apply as an ecological tool. Temperature dependencies are emphasized with the ultimate aim of linking such a description of photosynthesis with equations describing the energy budget of particular leaves. The description of photosynthesis can be applied toC 4 plants at this time and is needed to describe photosynthesis inC 3 plants when photorespiration is included. If the model is used to analyze at various times the response of a plant adjusting its metabolism to changes in light, temperature, or other factors experienced during growth, we will obtain a dynamic picture of the acclimation process. It will also be possible to determine the phenotypic plasticity of particular plants with respect to the metabolic sub-processes outlined.

Competition and stability in plant mixtures in the presence of disease.

A deterministic mathematical model is developed for competition between two plant species (or genotypes) in the presence of a host-specific pathogen capable of attacking one of the species only. The complexity of the plant-plant-pathogen interaction precluded precise mathematical description of all possible long-term outcomes. However, extensive computer simulation shows that stability is not an inevitable consequence of the differential interaction, rather, the outcome depends greatly upon the growth rates and relative competitive abilities of the plant species and on the transmission efficiency of the pathogen and its effect on individual host plants. The model confirmed the general validity of previous intuitive arguments but clearly indicated that the occurrence of inflected yield curves is not a sufficient indication in itself of long-term stability.

Analysis of gas exchange in seedlings of Acer saccharum: integration of field and laboratory studies.

In the field, photosynthesis of Acer saccharum seedlings was rarely light saturated, even though light saturation occurs at about 100 µmol quanta m-2 s-1 photosynthetic photon flux density (PPFD). PPFD during more than 75% of the daylight period was 50 µmol m-2 s-1 or less. At these low PPFD's there is a marked interaction of PPFD with the initial slope (CE) of the CO2 response. At PPFD-saturation CE was 0.018 µmol m-2 s-1/(µl/l). The apparent quantum efficiency (incident PPFD) at saturating CO2 was 0.05-0.08 mol/mol. [Formula: see text] and PPFD-saturated CO2 exchange was 6-8 µmol m-2 s-1. The ratio of internal CO2 concentration to external (C i /C a ) was 0.7 to 0.8 except during sunflecks when it decreased to 0.5. The decrease in C i /C a during sunflecks was the result of the slow response of stomates to increased PPFD compared to the response of net photosynthesis. An empirical model, which included the above parameters was used to simulate the measured CO2 exchange rate for portions of two days. Parameter values for the model were determined in experiments separate from the daily time courses being sumulated. Analysis of the field data, partly through the use of simulations, indicate that the elimination of sunflecks would reduce net carbon gain by 5-10%.

The diurnal time course of net photosynthesis of soybean leaves: Analysis with a physiologically based steady-state photosynthesis model.

A physiologically based steady-state model of whole leaf photosynthesis (WHOLEPHOT) is used to analyze observed net photosynthesis daily time courses of soybean, Glycine max (L.) Merr., leaves. Observations during two time periods of the 1978 growing season are analyzed and compared. After adjustment of the model for soybean, net photosynthesis rates are calculated with the model in response to measured incident light intensity, leaf temperature, air carbon dioxide concentration, and leaf diffusion resistance. The steady-state calculations closely approximate observed net photosynthesis. Results of the comparison reveal a decrease in photosynthetic capacity in leaves sampled during the second time period, which is associated with decreasing ability of leaves to respond to light intensity and internal air space carbon dioxide concentration, increasing mesophyll resistance, and increasing stomatal resistance.

Development of a photosynthesis model with an emphasis on ecological applications : III. Carbon dioxide and oxygen dependencies.

A theoretical description of the simultaneous processes of photosynthesis and photorespiration in a single leaf is developed, based on the hypothesis that carbon dioxide and oxygen compete for the active site of ribulose diphosphate carboxylase. Michaelis-Menten kinetics and competitive inhibition at the end of a diffusion path provide the basic structure of the model. Data of Ludwig (1972) from sunflower are analyzed according to the formulation. This description is part of a more general physiological-ecological model of photosynthesis presented previously (Tenhunen et al., 1976a, b) and continues to elaborate sub-processes in terms of physiologically meaningful parameters. The description is considered a working hypothesis. Data on photorespiration from the literature are reviewed as they relate to this working hypothesis. Several lines of investigation are thereby suggested that will help clarify the role of photorespiration in whole leaf photosynthesis and determine the over-all utility of this modeling approach.