ABSTRACT
Species ecology and life history patterns are often reflected in animal morphology. Blue whales are globally distributed, with distinct populations that feed in different productive coastal regions worldwide. Thus, they provide an opportunity to investigate how regional ecosystem characteristics may drive morphological differences within a species. Here, we compare physical and biological oceanography of three different blue whale foraging grounds: (1) Monterey Bay, California, USA; (2) the South Taranaki Bight (STB), Aotearoa New Zealand; and (3) the Corcovado Gulf, Chile. Additionally, we compare the morphology of blue whales from these regions using unoccupied aircraft imagery. Monterey Bay and the Corcovado Gulf are seasonally productive and support the migratory life history strategy of the Eastern North Pacific (ENP) and Chilean blue whale populations, respectively. In contrast, the New Zealand blue whale population remains in the less productive STB year-round. All three populations were indistinguishable in total body length. However, New Zealand blue whales were in significantly higher body condition despite lower regional productivity, potentially attributable to their non-migratory strategy that facilitates lower risk of spatiotemporal misalignment with more consistently available foraging opportunities. Alternatively, the migratory strategy of the ENP and Chilean populations may be successful when their presence on the foraging grounds temporally aligns with abundant prey availability. We document differences in skull and fluke morphology between populations, which may relate to different feeding behaviors adapted to region-specific prey and habitat characteristics. These morphological features may represent a trade-off between maneuverability for prey capture and efficient long-distance migration. As oceanographic patterns shift relative to long-term means under climate change, these blue whale populations may show different vulnerabilities due to differences in migratory phenology and feeding behavior between regions. Spanish abstract La ecología y patrones de historia de vida de las especies a menudo se reflejan en la morfología animal. Las ballenas azules están distribuidas globalmente, con poblaciones separadas que se alimentan en diferentes regiones costeras productivas de todo el mundo. Por lo tanto, brindan la oportunidad de investigar cómo las características regionales de los ecosistemas pueden impulsar diferencias morfológicas dentro de una especie. Aquí, comparamos la oceanografía física y biológica de tres zonas de alimentación diferentes de la ballena azul: (1) Bahía de Monterey, California, EE. UU., (2) Bahía del sur de Taranaki (BST), Nueva Zelanda, y (3) Golfo de Corcovado, Chile. Adicionalmente, comparamos la morfología de las ballenas azules de estas regiones utilizando imágenes de aeronaves no tripuladas. La Bahía de Monterey y el Golfo de Corcovado son estacionalmente productivos y apoyan la estrategia migratoria de la historia de vida de las poblaciones de ballena azul chilena y del Pacífico Norte Oriental (PNO), respectivamente. Por el contrario, la población de ballena azul de Nueva Zelanda permanece en la menos productiva BST durante todo el año. Las tres poblaciones eran indistinguibles en cuanto a la longitud corporal total. Sin embargo, las ballenas azules de Nueva Zelanda tenían una condición corporal significativamente mayor a pesar de una menor productividad regional, potencialmente atribuible a su estrategia no migratoria que facilita un menor riesgo de desalineación espaciotemporal con oportunidades de alimentación disponibles de manera más consistente. Alternativamente, la estrategia migratoria de las poblaciones de ballenas PNO y chilena puede tener éxito cuando su presencia en las zonas de alimentación se alinea temporalmente con la abundante disponibilidad de presas. Documentamos diferencias en la morfología del cráneo y la aleta caudal entre poblaciones, que pueden estar relacionadas con diferentes comportamientos de alimentación adaptados a las características de hábitat y presas específicas para cada región. Estas características morfológicas pueden representar una compensación entre la maniobrabilidad para la captura de presas y una migración eficiente a larga distancia. A medida que los patrones oceanográficos cambian en términos de mediano a largo plazo debido al cambio climático, estas poblaciones de ballenas azules pueden mostrar diferentes vulnerabilidades debido a diferencias en la fenología migratoria y el comportamiento de alimentación entre regiones.
ABSTRACT
Shock ignition enables high gain at low implosion velocity, reducing ablative Rayleigh-Taylor instability growth, which can degrade conventional direct drive. With this method, driving a strong shock requires high laser power and intensity, resulting in inefficiencies in the drive and the generation of hot electrons that can preheat the fuel. A new "shock-augmented ignition" pulse shape is described that, by preconditioning the ablation plasma before launching a strong shock, enables the shock ignition of thermonuclear fuel, but importantly, with substantially reduced laser power and intensity requirements. The reduced intensity requirement with respect to shock ignition limits laser-plasma instabilities, such as stimulated Raman and Brillouin scatter, reducing the risk of hot-electron preheat and restoring the laser coupling advantages of conventional direct drive. Simulations indicate that, due to the reduced power requirements, high gain (â¼100) ignition of large-scale direct drive implosions (outer radius â¼1750 µm, deuterium-tritium ice thickness â¼165 µm) may be possible within the power and energy limits of existing facilities such as the National Ignition Facility. Moreover, this concept extends to indirect drive implosions, which exhibit substantial yield increases at reduced implosion velocity. Shock-augmented ignition expands the viable design space of laser inertial fusion.
ABSTRACT
BACKGROUND: The present study aims to investigate the effectiveness of the Unified Protocol (UP), a transdiagnostic treatment of emotional disorders (EDs), when applied in a group format in the public mental health system in Spain. METHODS: 488 participants with a primary diagnosis of ED were randomized to the UP group or to the treatment as usual (TAU; individual, disorder-specific cognitive behavioral therapy). Personality, depression and anxiety symptoms, affect, and quality of life were assessed at pre-treatment, 3 months after treatment onset (coinciding with the end of the UP treatment), and 6 and 9 months after treatment onset (follow-ups). The moderating effect of the treatment condition and the number of sessions received in the evolution of study outcomes was investigated with a linear mixed model analysis. RESULTS: A significant improvement in outcomes occurred in both conditions, except for extraversion in the TAU. Improvements in depression, anxiety and quality of life were larger in the UP condition. After the treatment, improvements were maintained at follow-ups in all study outcomes. An interaction between Time*Condition*Sessions was found for depression. CONCLUSION: The results add to the existing evidence on the effectiveness of the UP and may be important for implementation purposes in the Spanish or other similar public mental health systems. Trial registration number NCT03064477 (March 10, 2017).
Subject(s)
Mood Disorders , Quality of Life , Follow-Up Studies , Humans , Mood Disorders/therapy , Quality of Life/psychology , Spain , Treatment OutcomeABSTRACT
We use a subignition scale laser, the 30 kJ Omega, and a novel shallow-cone target to study laser-plasma interactions at the ablation-plasma density scale lengths and laser intensities anticipated for direct drive shock-ignition implosions at National Ignition Facility scale. Our results show that, under these conditions, the dominant instability is convective stimulated Raman scatter with experimental evidence of two plasmon decay (TPD) only when the density scale length is reduced. Particle-in-cell simulations indicate this is due to TPD being shifted to lower densities, removing the experimental back-scatter signature and reducing the hot-electron temperature. The experimental laser energy-coupling to hot electrons was found to be 1%-2.5%, with electron temperatures between 35 and 45 keV. Radiation-hydrodynamics simulations employing these hot-electron characteristics indicate that they should not preheat the fuel in MJ-scale shock ignition experiments.
ABSTRACT
This paper presents a statistical method for the calculation of gaseous flux and diffusion coefficients through a Knudsen-regime cylindrical nanopore. A general integral formula for the flux is derived in terms of collision frequency, molecular density, and a scattering path length probability distribution. Under appropriate steady-state assumptions, the general formula simplifies to Fick's first law, from which an expression for the diffusion coefficient is derived. The model is shown to be dimensionally consistent with the Einstein relation. The conditions for agreement with Fick's second law are investigated. Using a model probability distribution the model leads to an expression for the diffusion coefficient for a pore of finite length. This result is shown to compare favorably with a classic formula from the literature.
ABSTRACT
The extracellular lipid matrix in the skin's outermost layer, the stratum corneum, is crucial for the skin barrier. The matrix is composed of ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs) and involves two lamellar phases: the short periodicity phase (SPP) and the long periodicity phase (LPP). To understand the skin barrier thoroughly, information about the molecular arrangement in the unit cell of these lamellar phases is paramount. Previously we examined the molecular arrangement in the unit cell of the SPP. Furthermore X-ray and neutron diffraction revealed a trilayer arrangement of lipids within the unit cell of the LPP [D. Groen et al., Biophysical Journal, 97, 2242-2249, 2009]. In the present study, we used neutron diffraction to obtain more details about the location of lipid (sub)classes in the unit cell of the LPP. The diffraction pattern revealed at least 8 diffraction orders of the LPP with a repeating unit of 129.6±0.5Å. To determine the location of lipid sub(classes) in the unit cell, samples were examined with either only protiated lipids or selectively deuterated lipids. The diffraction data obtained by means of D2O/H2O contrast variation together with a gradual replacement of one particular CER, the acyl CER, by its partly deuterated counterpart, were used to construct the scattering length density profiles. The acyl chain of the acyl CER subclass is located at a position of ~21.4±0.2Å from the unit cell centre of the LPP. The position and orientation of CHOL in the LPP unit cell were determined using tail and head-group deuterated forms of the sterol. CHOL is located with its head-group positioned ~26±0.2Å from the unit cell centre. This allows the formation of a hydrogen bond with the ester group of the acyl CER located in close proximity. Based on the positions of the deuterated moieties of the acyl CER, CHOL and the previously determined location of two other lipid subclasses [E.H. Mojumdar et al., Biophysical Journal, 108, 2670-2679, 2015], a molecular model is proposed for the unit cell of the LPP. In this model CHOL is located in the two outer layers of the LPP, while CER EOS is linking the two outer layers with the central lipid layers. Finally the two other lipid subclasses are predominantly located in the central layer of the LPP.
Subject(s)
Ceramides/analysis , Cholesterol/analysis , Epidermis/chemistry , Body Water , Deuterium Oxide/analysis , Epidermis/ultrastructure , Fatty Acids, Nonesterified/analysis , Fatty Acids, Nonesterified/chemistry , Linoleic Acid/analysis , Lipids/analysis , Lipids/chemistry , Molecular Structure , Neutron Diffraction , Skin AbsorptionABSTRACT
In arthritis of the varus knee, a high tibial osteotomy (HTO) redistributes load from the diseased medial compartment to the unaffected lateral compartment. We report the outcome of 36 patients (33 men and three women) with 42 varus, arthritic knees who underwent HTO and dynamic correction using a Garches external fixator until they felt that normal alignment had been restored. The mean age of the patients was 54.11 years (34 to 68). Normal alignment was achieved at a mean 5.5 weeks (3 to 10) post-operatively. Radiographs, gait analysis and visual analogue scores for pain were measured pre- and post-operatively, at one year and at medium-term follow-up (mean six years; 2 to 10). Failure was defined as conversion to knee arthroplasty. Pre-operative gait analysis divided the 42 knees into two equal groups with high (17 patients) or low (19 patients) adductor moments. After correction, a statistically significant (p < 0.001, t-test,) change in adductor moment was achieved and maintained in both groups, with a rate of failure of three knees (7.1%), and 89% (95% confidence interval (CI) 84.9 to 94.7) survivorship at medium-term follow-up. At final follow-up, after a mean of 15.9 years (12 to 20), there was a survivorship of 59% (95% CI 59.6 to 68.9) irrespective of adductor moment group, with a mean time to conversion to knee arthroplasty of 9.5 years (3 to 18; 95% confidence interval ± 2.5). HTO remains a useful option in the medium-term for the treatment of medial compartment osteoarthritis of the knee but does not last in the long-term. Cite this article: Bone Joint J 2016;98-B:601-7.
Subject(s)
External Fixators , Gait/physiology , Osteoarthritis, Knee/surgery , Osteotomy/methods , Tibia/surgery , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Osteoarthritis, Knee/physiopathology , Range of Motion, Articular/physiology , Visual Analog ScaleABSTRACT
Relatively little is known about how drug self-association influences absorption into the human body. This study presented two hydrophobic membranes with a series of solutions containing different types of tetracaine aggregates with the aim of understanding how the attributes of supramolecular aggregate formation influenced passive membrane transport. The data showed that aqueous solutions of the unprotonated form of tetracaine displayed a significantly higher (p<0.05) passive membrane transport compared to solutions with mixtures of the unprotonated and protonated drug microspecies (e.g. transport through the skin was 0.96±0.31µgcm(-2)min(-1) and 1.59±0.26µgcm(-2)min(-1) respectively). However, despite an enhanced rate of drug transport and a better membrane partitioning the unionised molecules showed a significantly longer (p<0.05) lag time to membrane penetration compared solutions rich in the ionised microspecies. Analytical characterisation of the solutions applied to the apical surface of the membranes in the transport studies showed that larger tetracaine aggregates with smaller surface charge gave rise to the longer lag times. These large aggregates demonstrated more extensive intermolecular bonding and therefore, it was suggest that it was the enhanced propensity of the unionised species to form tightly bound drug aggregates that caused the delay in the membrane penetration.
Subject(s)
Biological Transport/drug effects , Cell Membrane/metabolism , Pharmaceutical Preparations/administration & dosage , Pharmaceutical Preparations/chemistry , Animals , Hydrophobic and Hydrophilic Interactions , Skin/metabolism , Solutions/chemistry , Swine , Tetracaine/administration & dosage , Tetracaine/chemistryABSTRACT
OBJECTIVES: A patient-centred approach, usually achieved through shared decision making, has the potential to help improve decision making around knee arthroplasty surgery. However, such an approach requires an understanding of the factors involved in patient decision making. This review's objective is to systematically examine the qualitative literature surrounding patients' decision making in knee arthroplasty. METHODS: A systematic literature review using Medline and Embase was conducted to identify qualitative studies that examined patients' decision making around knee arthroplasty. An aggregated account of what is known about patients' decision making in knee arthroplasties is provided. RESULTS: Seven studies with 234 participants in interviews or focus groups are included. Ten themes are replicated across studies, namely: expectations of surgery; coping mechanisms; relationship with clinician; fear; pain; function; psychological implications; social network; previous experience of surgery; and conflict in opinions. CONCLUSIONS: This review is helpful in not only directing future research to areas that are not understood, or require confirmation, but also in highlighting areas that future interventions could address. These include those aimed at delivering information, which are likely to affect the satisfaction rate, demand, and use of knee arthroplasties. Cite this article: Bone Joint Res 2015;4;163-169.
ABSTRACT
Langmuir surface pressure, small-angle neutron scattering (SANS), and neutron reflectivity (NR) studies have been performed to determine how formulation of the antifungal drug amphotericin B (AmB), with sodium cholesteryl sulfate (SCS)-as in Amphotec-affects its interactions with ergosterol-containing (model fungal cell) and cholesterol-containing (model mammalian cell) membranes. The effects of mixing AmB in 1:1 molar ratio with cholesteryl sulfate (yielding AmB-SCS micelles) are compared against those of free AmB, using monolayers and bilayers formed from palmitoyloleoylphosphatidylcholine (POPC) in the absence and presence of 30 mol % ergosterol or cholesterol, in all cases employing a 1:0.05 molar ratio of lipid:AmB. Analyses of the (bilayer) SANS and (monolayer) NR data indicate that the equilibrium changes in membrane structure induced in sterol-free and sterol-containing membranes are the same for free AmB and AmB-SCS. Stopped-flow SANS experiments, however, reveal that the structural changes to vesicle membranes occur far more rapidly following exposure to AmB-SCS vs free drug, with the kinetics of these changes varying with membrane composition. With POPC vesicles, the structural changes induced by AmB-SCS become apparent only after several minutes, and equilibrium is reached after â¼30 min. The corresponding onset of changes in POPC-ergosterol and POPC-cholesterol vesicles, however, occurs within â¼5 s, with equilibrium reached after 10 and 120 s, respectively. The rate of insertion of AmB into POPC-sterol membranes is thus increased through formulation as AmB-SCS. Moreover, the differences in monolayer surface pressure and SANS structure-change equilibration times suggest significant rearrangement of AmB within these membranes following insertion. The reduced times to equilibrium for the POPC-ergosterol vs POPC-cholesterol systems are consistent with the known differences in affinity of AmB for these two sterols, and the reduced time to equilibrium for AmB-SCS interaction with POPC-ergosterol membranes vs that for free AmB is consistent with the reduced host toxicity of Amphotec.
Subject(s)
Amphotericin B/chemistry , Cholesterol Esters/chemistry , Membranes, Artificial , Phospholipids/chemistry , Phosphatidylcholines/chemistryABSTRACT
The Gamma-to-Electron Magnetic Spectrometer (GEMS) diagnostic is designed to measure the prompt γ-ray energy spectrum during high yield deuterium-tritium (DT) implosions at the National Ignition Facility (NIF). The prompt γ-ray spectrum will provide "burn-averaged" observables, including total DT fusion yield, total areal density (ρR), ablator ρR, and fuel ρR. These burn-averaged observables are unique because they are essentially averaged over 4π, providing a global reference for the line-of-sight-specific measurements typical of x-ray and neutron diagnostics. The GEMS conceptual design meets the physics-based requirements: ΔE/E = 3%-5% can be achieved in the range of 2-25 MeV γ-ray energy. Minimum DT neutron yields required for 15% measurement uncertainty at low-resolution mode are: 5 × 10(14) DT-n for ablator ρR (at 0.2 g/cm(2)); 2 × 10(15) DT-n for total DT yield (at 4.2 × 10(-5) γ/n); and 1 × 10(16) DT-n for fuel ρR (at 1 g/cm(2)).
ABSTRACT
We present data that indicate nonuniform magnetization loss due to radiation damage in neodymium-iron-boron Halbach-style permanent magnet quadrupoles. The proton radiography (pRad) facility at Los Alamos uses permanent-magnet quadrupoles for magnifying lenses, and a system recently commissioned at GSI-Darmsdadt uses permanent magnets for its primary lenses. Large fluences of spallation neutrons can be produced in close proximity to these magnets when the proton beam is, intentionally or unintentionally, directed into the tungsten beam collimators; imaging experiments at LANL's pRad have shown image degradation with these magnetic lenses at proton beam doses lower than those expected to cause damage through radiation-induced reduction of the quadrupole strength alone. We have observed preferential degradation in portions of the permanent magnet quadrupole where the field intensity is highest, resulting in increased high-order multipole components.
ABSTRACT
Langmuir isotherm, neutron reflectivity, and Brewster angle microscopy experiments have been performed to study the interaction of amphotericin B (AmB) with monolayers prepared from 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and mixtures of this lipid with cholesterol or ergosterol to mimic mammalian and fungal cell membranes, respectively. Isotherm data show that AmB causes a more pronounced change in surface pressure in the POPC/ergosterol system than in the POPC and POPC/cholesterol systems, and its interaction with the POPC/ergosterol monolayer is also more rapid than with the POPC and POPC/cholesterol monolayers. Brewster angle microscopy shows that, in interaction with POPC monolayers, AmB causes the formation of small domains which shrink and disappear within a few minutes. The drug also causes domain formation in the POPC/cholesterol and POPC/ergosterol monolayers; in the former case, these are formed more slowly than is seen with the POPC monolayers and are ultimately much smaller; in the latter case, they are formed rather more quickly and are more heterogeneous in size. Neutron reflectivity data show that the changes in monolayer structure following interaction with AmB are the same for all three systems studied: the data are consistent with the drug inserting into the monolayers with its macrocyclic ring intercalated among the lipid acyl chains and sterol ring systems, with its mycosamine moiety colocalizing with the sterol hydroxyl and POPC head groups. On the basis of these studies, it is concluded that AmB inserts in a similar manner into POPC, POPC/cholesterol, and POPC/ergosterol monolayers but does so with differing kinetics and with the formation of quite different in-plane structures. The more rapid time scale for interaction of the drug with the POPC/ergosterol monolayer, its more pronounced effect on monolayer surface pressure, and its more marked changes as regards domain formation are all consistent with the drug's selectivity for fungal vs mammalian cell membranes.
Subject(s)
Amphotericin B/chemistry , Ergosterol/chemistry , Phosphatidylcholines/chemistryABSTRACT
RESEARCH QUESTION: What is the individualized bleeding experience of women with fibroids and anaemia in a 3 month randomized placebo controlled trial (PEARL I) of the selective progesterone receptor modulator (SPRM), ulipristal acetate (UPA)? SUMMARY ANSWER: In contrast to continuing excessive regular menstruation in the placebo group, a majority of women treated with UPA (63.1% of those on 5 mg/day and 71.3% of those on 10 mg/day) experienced the rapid onset of amenorrhoea or minimal blood loss [pictorial blood loss assessment chart (PBAC) < 12]. The remainder experienced various patterns of bleeding and intensity of blood loss that are described for the first time, including an association of irregular bleeding on UPA with sub-mucous fibroids. WHAT IS KNOWN ALREADY: The majority experience on UPA is amenorrhoea but the bleeding experience of the others has not been characterized. STUDY DESIGN, SIZE, DURATION: A 13 week randomized controlled trial in women, eligible for surgery for uterine fibroids and anaemia, comparing placebo (n = 48), UPA 5 mg (n = 95) or UPA 10 mg (n = 94). The treatment aim was fibroid shrinkage and the primary definitions and outcomes are published elsewhere; here the secondary outcome measure of vaginal bleeding pattern is described. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women, 18-50 years old, with fibroids and haemoglobin ≤10.2 g/dl, justifying surgery. At least one fibroid was 3-10 cm diameter and uterus ≤16 weeks pregnancy size. All used the daily PBAC methodology in a screening cycle (Ps) and throughout treatment, and for the 4 weeks preceding Week 26 and Week 38 in those who did not have surgery. An excessive menstruation is PBAC > 100. The bleeding patterns were characterized using the classification of Belsey, developed under auspices of WHO. MAIN RESULTS AND THE ROLE OF CHANCE: In the placebo group, all women had an excessive screening PBAC [median 376; interquartile range (IQR) 241-574]; 81.3% of them had regular menstrual bleeding and the intensity of bleeding remained similar, so that the median PBAC in the next three periods was 90, 92 and 93% of the screening value. Four of the 48 women had spontaneous improvement in bleeding and one developed amenorrhoea and elevation of gonadotrophins. In the placebo group, 22 women provided Week 26 and 21 women provided Week 38 PBAC data. The median Week 26 PBAC (312: IQR 102-524) and Week 38 PBAC (236; IQR 103-465) indicated ongoing excessive bleeding. In the UPA group, screening PBAC confirmed excessive bleeding (UPA 5 mg, median 358; IQR 232-621; UPA 10 mg, median 330; IQR 235-542). UPA was initiated from the start of a menstruation (P1) and no women had regular periods on treatment. Following P1 through the whole of the remaining 13 weeks of UPA treatment amenorrhoea or minimal loss (PBAC < 12 for whole phase) occurred in 63.1% (UPA 5 mg) or 71.3% (UPA 10 mg). The characterization of the individualized bleeding experience of the remaining women on 5 mg and 10 mg UPA, respectively, were infrequent bleeding in 17.9 and 12.8%; frequent or prolonged bleeding or both in 12.7 and 11.7% and irregular bleeding in 5.3 and 3.2%. In those with prolonged, frequent or irregular bleeding there was a high chance that sub-mucous fibroids were present (UPA 5 mg 100% and UPA 10 mg 78.6%) but no correlation with progesterone receptor modulator-associated endometrial changes. LIMITATIONS, REASONS FOR CAUTION: The follow-up PBAC data at Week 26 and Week 38 are only valid for women who did not have surgical intervention. These groups may not be representative of the groups at screening. WIDER IMPLICATIONS OF THE FINDINGS: This first detailed description of these SPRM bleeding patterns provides clinicians with an indication of potential responses in women using the SPRM UPA and provides an extended definition of bleeding in untreated women with excessive bleeding and fibroids. STUDY FUNDING/COMPETING INTEREST(S): Funded by PregLem/Gedeon Richter. D.H.B. is a member of the Scientific Advisory Board of PregLem, and in this role participated in the study design and supervision. Stock originally held in PregLem was given up when PregLem was incorporated into Gedeon Richter; D.H.B. does not currently hold stock. M.A.L. has received payment from Gideon Richter to attend a meeting to present these data (Barcelona, April 2013) but no financial support in preparing the manuscript. B.C.J.M.F. is a member of the Scientific Advisory Board of PregLem and has received fees and grant support from the following companies: Andromed, Ardana, Auxogyn, Ferring, Genovum, Gedeon Richter, Merck Serono, MSD, Organon, Pantharei Bioscience, PregLem, Roche, Schering, Schering Plough, Serono, Watson Laboratories and Wyeth. P.T. is a paid statistical consultant for PregLem SA. E.B. is a full time employee of PregLem and received payment from stocks sold in October 2010 from the company's full acquisition by Gedeon Richter Group. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT00755755 (PEARL I).
Subject(s)
Leiomyoma/drug therapy , Norpregnadienes/therapeutic use , Uterine Hemorrhage/drug therapy , Uterine Neoplasms/drug therapy , Adolescent , Adult , Amenorrhea/chemically induced , Double-Blind Method , Female , Humans , Leiomyoma/complications , Menorrhagia/drug therapy , Middle Aged , Norpregnadienes/administration & dosageABSTRACT
The intercellular lipid matrix of the skin's stratum corneum serves to protect the body against desiccation and simultaneously limits the passage of drugs and other xenobiotics into the body. The matrix is made up of ceramides, free fatty acids, and cholesterol, which are organized as two coexisting crystalline lamellar phases. In studies reported here, we sought to use the technique of neutron diffraction, together with the device of isotopic (H/D) substitution, to determine the molecular architecture of the lamellar phase having a repeat distance of 53.9 ± 0.3 Å. Using hydrogenous samples as well as samples incorporating perdeuterated (C24:0) fatty acids and selectively deuterated cholesterol, the diffraction data obtained were used to construct neutron scattering length density profiles. By this means, the locations within the unit cell were determined for the cholesterol and fatty acids. The cholesterol headgroup was found to lie slightly inward from the unit cell boundary and the tail of the molecule located 6.2 ± 0.2 Å from the unit cell center. The fatty acid headgroups were located at the unit cell boundary with their acyl chains straddling the unit cell center. Based on these results, a molecular model is proposed for the arrangement of the lipids within the unit cell.
Subject(s)
Cell Membrane/chemistry , Cell Membrane/metabolism , Cholesterol/chemistry , Cholesterol/metabolism , Fatty Acids/chemistry , Fatty Acids/metabolism , Neutron Diffraction , Biological Transport , Ceramides/chemistry , Ceramides/metabolism , Epidermal Cells , HumansABSTRACT
The best method of fixation for clavicle fractures is not known. The purpose of this review was to examine the evidence comparing plate and intramedullary fixation for midshaft clavicle fractures. A search of MEDLINE in September 2011 identified five papers that compared plate and intramedullary fixation, and fulfilled our eligibility criteria, consisting of; one randomised controlled trial, two quasi-randomised controlled trials, and two retrospective studies. Level of evidence was assessed using the Scottish Intercollegiate Guidelines Network guidance and the Cochrane Bone, Joint and Muscle Trauma Group's quality assessment tool. No attempt at meta-analysis was made due to the heterogeneity of the study populations and interventions. We found no difference between intramedullary fixation and plate fixation. There was a trend towards a lower complication rate with intramedullary fixation. On the basis of the available evidence, we would advocate both techniques for the treatment of midshaft clavicle fractures.
Subject(s)
Bone Plates , Clavicle/injuries , Fracture Fixation, Internal , Fracture Fixation, Intramedullary , Fractures, Bone/surgery , Clavicle/surgery , Female , Fractures, Bone/epidemiology , Humans , Male , Postoperative Complications/epidemiology , Randomized Controlled Trials as Topic , Recovery of Function , Scotland/epidemiology , Treatment OutcomeABSTRACT
AIMS: Osteoid osteoma and osteoblastoma have, in the past, been variously regarded as both similar and distinct entities. Currently, WHO classifies these tumours separately. We compared archetypal cases to identify novel histomorphological and immunohistochemical features attempting to clarify their mutual relationship. METHODS AND RESULTS: 10 osteoid osteomas and 20 osteoblastomas (10 spinal and 10 non-spinal) were retrieved and reviewed clinically, radiologically and histologically. Immunohistochemistry was performed for: desmin, SMA, neurofilament, S100, vimentin, PGP9.5, GFAP, EMA, caldesmon, CD34, broad-spectrum cytokeratins, claudin-1. We identified features, common to both osteoid osteoma and osteoblastoma, namely, areas of lesional non-osteoblastic stroma and the presence of scattered, large cells with smudged/degenerate nuclei. Immunohistochemically, we confirmed the innervated status of osteoid osteomas, and found that osteoblastomas were similarly innervated. The non-osteoblastic lesional stroma was distinctive owing to expression of EMA and NSE by the mesenchymal spindle cells and expression of desmin, PGP9.5 and S100 by the scattered, large cells with 'smudged' nuclei. CONCLUSIONS: Both osteoid osteoma and osteoblastoma are innervated bone-forming lesions which share novel histomorphological and immunohistochemical features supporting the view that separate classification is unjustified, and we offer a pathogenetic explanation for their apparent clinical and radiological variance.
Subject(s)
Bone Neoplasms/pathology , Osteoblastoma/pathology , Osteoma, Osteoid/pathology , Adolescent , Adult , Biomarkers, Tumor/metabolism , Bone Neoplasms/metabolism , Child , Child, Preschool , Female , Humans , Immunohistochemistry , Male , Osteoblastoma/metabolism , Osteoma, Osteoid/metabolismABSTRACT
INTRODUCTION: Plaster of Paris (PoP) impregnated bandages have been used to maintain the position of bones and joints for over a century. Classically, wool dressing is applied to the limb before the PoP, which can then be moulded to the desired shape. A modification of this practice is to wrap the PoP bandages circumferentially in cotton before wetting and applying to the patient in an attempt to reduce inhalation of plaster dust and reduce mess. However, this may affect the water content of the cast and therefore also its setting properties and strength. This study compared the setting properties of PoP casts when used with and without cotton wrapping. METHODS: Sixty specimens, compliant with the American Society for Testing and Materials standards for three-point bending tests, were prepared, with thirty wrapped in cotton. All were weighed before and after water immersion, and wrapped around a plastic cylinder to mimic limb application. Bending stiffness and yield strength was measured on a servohydraulic materials testing machine at 2, 6, 12, 24, 48 and 72 hours. RESULTS: The water content of cotton-wrapped plaster was significantly higher (50%) than that of standard plaster. It had significantly lower strength up to 24 hours and significantly lower stiffness up to 72 hours. CONCLUSIONS: The initial decrease in strength and stiffness of the cast wrapped in cotton may comprise the ability of the backslab to hold the joint or bone in an optimal position. Any modification of the standard plaster slab application technique should allow for the potential adverse effects on the plaster setting properties.
Subject(s)
Calcium Sulfate/chemistry , Casts, Surgical/standards , Cotton Fiber , Bandages , Hardness , Pliability , Time Factors , Water/analysisABSTRACT
INTRODUCTION: More than 150,000 hip and knee joint replacements are carried out in the United Kingdom yearly, and variations in length of stay [LOS] affects the overall costs of the procedures. This audit assesses the effect of the introduction of specialist ward on LOS following arthroplasty. METHOD: A combination of prospective and retrospective data on length of stay, demographics, and surgical site infections [SSI] were collected for the six months before and six months after the specialist ward was opened. Primary lower limb arthroplasty data was evaluated. American Society of Anaesthesiologists Physical Status Scores [ASA] for all admissions for lower limb arthroplasty were compared. RESULTS: Mean LOS for 222 patients managed in general orthopaedic wards was 7.61 days compared to 5.67 days for 191 patients managed in a dedicated arthroplasty ward. Three surgical site infections [SSIs] were noted in the general ward compared to zero in the specialist ward. CONCLUSIONS: This audit demonstrates a two-day reduction in LOS for patients managed in a ring-fenced ward. The cause of the reduction is multifactorial and not solely due to a trend for reduced SSI but influenced by many other changes cascading from the original organisational revision. Overall reduced stay however can only increase efficiency if downstream resources are available. Other units may wish to explore the benefits from similar dedicated wards in response to a growing demand for arthroplasty within a system of fixed resources.