Successful pregnancy and delivery in a woman with panhypopituitarism

To The Editor: Pregnancy after a complete loss of hypophyseal function is rare. Lack of growth hormone (GH), adrenocorticotropin (ACTH) and thyroid-stimulating hormone (TSH) in childhood may result in malfunction of different organ systems, affecting fertility. Complete lack of ovarian stimulation by FSH and LH results in anovulation and ovarian atrophy. We present a patient with panhypopituitarism who has achieved pregnancy and delivered through in vitro fertilization (IVF) and embryo transfer (ET). This 35 year-old woman underwent four trans-sphenoidal hypophysectomies at 12, 13, 23 and 26 years of age, for recurrent neuroectodermal cysts (embryonic remnant). Her second operation was complicated by panhypopituitarism with severe diabetes insipidus, treated with adequate doses of hydrocortisone, L-thyroxine and desmopressin. At age 21, cyclic substitution therapy with estrogen and progesterone was given for primary amenorrhea. Two years later, GH therapy was added. At age 33, she requested fertility treatment. GH, cyclic estrogen, and progesterone therapy were stopped, and she underwent ovulation induction, with gonadotropins, followed by IVF and ET, resulting in a successful dichorionic twin pregnancy. She was followed regularly at a combined antenatal clinic. No changes in steroid, desmopressin, or thyroxine doses were required, and the antenatal period was uneventful. An elective caesarean section was performed at 37 weeks gestation, and healthy twin boys (weighing 3.0 and 3.14 kg) were delivered. Clinical course during puerperium was normal.Conception and uncomplicated pregnancy in patients with hypopituitiarism are rare [1,2]. Well-timed substitution of missing hormones enables normal physical development. Stimulation therapy with gonadotropins can induce adequate follicular maturation. IVF-ET may be a useful treatment for infertility in patients with hypopituitarism as it may reduce the incidence of multiple pregnancies associated with higher risk in GH deficient patients

Black swans, cognition and the power of learning from failure

Failure carries undeniable stigma and is difficult to confront for individuals, teams, and organizations. Disciplines such as commercial and military aviation, medicine, and business have long histories of grappling with it, beginning with the recognition that failure is inevitable in every human endeavor. While conservation may arguably be more complex, conservation professionals can draw upon the research and experience of these other disciplines to institutionalize activities and attitudes that foster learning from failures, whether they are minor setbacks or major disasters. Understanding the role of individual cognitive biases, team psychological safety, and organizational willingness to support critical self-examination all contribute to creating a cultural shift in conservation to one that is open to the learning opportunity that failure provides. This new approach to managing failure is a necessary next step in the evolution of conservation effectiveness. This article is protected by copyright. All rights reserved

Special care dentistry trainee views on the medical and oral medicine elements of the specialist training curriculum

Introduction Specialty training curricula are subject to periodic update, and trainee views are an important element in identifying which areas need particular focus. In this study, we wished to examine specialty trainee opinions on two areas of a curriculum for special care dentistry, in particular oral medicine, and the component elements of related systemic disease and therapies (RSDT), namely pathology, pharmacology and therapeutics, and human systemic disease. Materials and methods Following ethical approval, we identified 35 specialty registrars in special care dentistry in the UK and Ireland who were invited to use an online survey tool to gather demographic data and then to ask their views on the delivery of training in oral medicine and RSDT. Respondents were also asked whether sufficient importance was placed on these topics and whether they could be accessed and delivered appropriately. Results The 23 registrars surveyed comprised a representative group from all parts of the UK and Ireland and were at different stages of specialty training. The majority thought oral medicine and RSDT were key elements of the curriculum and could be given more prominence, especially in the context of an increasingly ageing population with associated oral manifestations of chronic disease, multiple drugs and disabilities. Discussion and conclusion The registrars surveyed felt that oral medicine and RSDT and were integral to training and that emphasis and opportunities for training in these areas could be improved, especially for those trainees based outside of a dental hospital setting

Optimisation of variables for studying dilepton transverse momentum distributions at hadron colliders

In future measurements of the dilepton ($Z/\gamma^*$) transverse momentum, \Qt, at both the Tevatron and LHC, the achievable bin widths and the ultimate precision of the measurements will be limited by experimental resolution rather than by the available event statistics. In a recent paper the variable \at, which corresponds to the component of \Qt\ that is transverse to the dilepton thrust axis, has been studied in this regard. In the region, \Qt\ $<$ 30 GeV, \at\ has been shown to be less susceptible to experimental resolution and efficiency effects than the \Qt. Extending over all \Qt, we now demonstrate that dividing \at\ (or \Qt) by the measured dilepton invariant mass further improves the resolution. In addition, we propose a new variable, \phistarEta, that is determined exclusively from the measured lepton directions; this is even more precisely determined experimentally than the above variables and is similarly sensitive to the \Qt. The greater precision achievable using such variables will enable more stringent tests of QCD and tighter constraints on Monte Carlo event generator tunes.Comment: 8 pages, 5 figures, 2 table

Motor crosslinking augments elasticity in active nematics

In active materials, uncoordinated internal stresses lead to emergent long-range flows. An understanding of how the behavior of active materials depends on mesoscopic (hydrodynamic) parameters is developing, but there remains a gap in knowledge concerning how hydrodynamic parameters depend on the properties of microscopic elements. In this work, we combine experiments and multiscale modeling to relate the structure and dynamics of active nematics composed of biopolymer filaments and molecular motors to their microscopic properties, in particular motor processivity, speed, and valency. We show that crosslinking of filaments by both motors and passive crosslinkers not only augments the contributions to nematic elasticity from excluded volume effects but dominates them. By altering motor kinetics we show that a competition between motor speed and crosslinking results in a nonmonotonic dependence of nematic flow on motor speed. By modulating passive filament crosslinking we show that energy transfer into nematic flow is in large part dictated by crosslinking. Thus motor proteins both generate activity and contribute to nematic elasticity. Our results provide new insights for rationally engineering active materials

Structuring Stress for Active Materials Control

Active materials are capable of converting free energy into mechanical work to produce autonomous motion, and exhibit striking collective dynamics that biology relies on for essential functions. Controlling those dynamics and transport in synthetic systems has been particularly challenging. Here, we introduce the concept of spatially structured activity as a means to control and manipulate transport in active nematic liquid crystals consisting of actin filaments and light-sensitive myosin motors. Simulations and experiments are used to demonstrate that topological defects can be generated at will, and then constrained to move along specified trajectories, by inducing local stresses in an otherwise passive material. These results provide a foundation for design of autonomous and reconfigurable microfluidic systems where transport is controlled by modulating activity with light

Ursodeoxycholic acid to reduce adverse perinatal outcomes for intrahepatic cholestasis of pregnancy: the PITCHES RCT

Background: Intrahepatic cholestasis of pregnancy, characterised by maternal pruritus and raised serum bile acid concentrations, is associated with increased rates of stillbirth, preterm birth and neonatal unit admission. Ursodeoxycholic acid is widely used as a treatment, but without an adequate evidence base. / Objective: We aimed to evaluate whether or not ursodeoxycholic acid reduces adverse perinatal outcomes in affected women. / Design: Multicentre, masked, randomised, placebo-controlled, two-arm, parallel-group trial. / Setting: Thirty-three UK maternity units. / Participants: Women with intrahepatic cholestasis of pregnancy aged ≥ 18 years, between 20+0 and 40+6 weeks’ gestation with a singleton or twin pregnancy and no known lethal fetal anomaly. / Interventions: Women were randomly assigned (1 : 1 allocation ratio) to take ursodeoxycholic acid tablets or matched placebo tablets, at an equivalent dose of 1000 mg daily, titrated as needed. / Main outcome measures: The primary outcome was a composite of perinatal death (in utero fetal death after randomisation or known neonatal death up to 7 days) or preterm delivery (< 37 weeks’ gestation) or neonatal unit admission for at least 4 hours (from birth until hospital discharge). Each infant was counted once within this composite. Analyses were by intention to treat. / Results: Between 23 December 2015 and 7 August 2018, 605 women were randomised, with 305 women allocated to the ursodeoxycholic acid arm and 300 women to the placebo arm. There was no evidence of a significant difference in the incidence of the primary outcome between the groups: 23.0% (74 out of 322 infants) in the ursodeoxycholic acid group compared with 26.7% (85 out of 318 infants) in the placebo group; adjusted risk ratio 0.85 (95% confidence interval 0.62 to 1.15). There was no evidence of a significant difference in total costs (maternal, infant and the cost of ursodeoxycholic acid) between the two trial groups. There were two serious adverse events in the ursodeoxycholic acid group and six in the placebo group. / Limitations: Limitations include a primary outcome event rate in the control group that was lower than that estimated for the sample size calculation, but the lack of evidence of effect in all analyses suggests that it is unlikely that the trial had insufficient power. / Conclusions: In this clinical trial of ursodeoxycholic acid in women with intrahepatic cholestasis of pregnancy, there is no evidence that it is effective in reducing a composite of adverse perinatal outcomes. / Future work: Future research should aim to elucidate the aetiology and pathophysiology of adverse perinatal outcomes, particularly stillbirth, in women with intrahepatic cholestasis of pregnancy to assist the development of an effective preventative treatment. Further exploratory analyses may identify groups of women who might respond to ursodeoxycholic acid treatment. / Trial registration: Current Controlled Trials ISRCTN91918806. / Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 9. See the NIHR Journals Library website for further project information

The design and characterization of a 300 channel, optimized full-band millimeter filterbank for science with SuperSpec

SuperSpec is an integrated, on-chip spectrometer for millimeter and sub-millimeter astronomy. We report the approach, design optimization, and partial characterization of a 300 channel filterbank covering the 185 to 315 GHz frequency band that targets a resolving power R ~ 310, and fits on a 3.5×5.5 cm chip. SuperSpec uses a lens and broadband antenna to couple radiation into a niobium microstrip that feeds a bank of niobium microstrip half-wave resonators for frequency selectivity. Each half-wave resonator is coupled to the inductor of a titanium nitride lumped-element kinetic inductance detector (LEKID) that detects the incident radiation. The device was designed for use in a demonstration instrument at the Large Millimeter Telescope (LMT)

B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al

Performance of the LHCb vertex locator

The Vertex Locator (VELO) is a silicon microstrip detector that surrounds the proton-proton interaction region in the LHCb experiment. The performance of the detector during the first years of its physics operation is reviewed. The system is operated in vacuum, uses a bi-phase CO2 cooling system, and the sensors are moved to 7 mm from the LHC beam for physics data taking. The performance and stability of these characteristic features of the detector are described, and details of the material budget are given. The calibration of the timing and the data processing algorithms that are implemented in FPGAs are described. The system performance is fully characterised. The sensors have a signal to noise ratio of approximately 20 and a best hit resolution of 4 μm is achieved at the optimal track angle. The typical detector occupancy for minimum bias events in standard operating conditions in 2011 is around 0.5%, and the detector has less than 1% of faulty strips. The proximity of the detector to the beam means that the inner regions of the n+-on-n sensors have undergone space-charge sign inversion due to radiation damage. The VELO performance parameters that drive the experiment's physics sensitivity are also given. The track finding efficiency of the VELO is typically above 98% and the modules have been aligned to a precision of 1 μm for translations in the plane transverse to the beam. A primary vertex resolution of 13 μm in the transverse plane and 71 μm along the beam axis is achieved for vertices with 25 tracks. An impact parameter resolution of less than 35 μm is achieved for particles with transverse momentum greater than 1 GeV/c