ABSTRACT
We demonstrate nonequilibrium steady-state photon transport through a chain of five coupled artificial atoms simulating the driven-dissipative Bose-Hubbard model. Using transmission spectroscopy, we show that the system retains many-particle coherence despite being coupled strongly to two open spaces. We find that cross-Kerr interaction between system states allows high-contrast spectroscopic visualization of the emergent energy bands. For vanishing disorder, we observe the transition of the system from the linear to nonlinear regime of photon blockade in excellent agreement with the input-output theory. Finally, we show how controllable disorder introduced to the system suppresses nonlocal photon transmission. We argue that proposed architecture may be applied to analog simulation of many-body Floquet dynamics with even larger arrays of artificial atoms paving an alternative way towards quantum supremacy.
ABSTRACT
A plasmonic grating consisting of parallel gold or silver nanowires on the glass substrate is an excellent sensor for refractive index measurement of a gas or liquid medium. We suggest measuring the local field in a gap between the wires to increase the sensitivity. The local electric field contains more information on the environment since it includes the evanescent waves. Calculation by the boundary element method confirms a substantial improvement of sensitivity owing to a sharp cusp-like gap resonance in the angular dependence. The local field measurement under the frustration of total internal reflection has promising prospects for the development of modern biomedical and chemical sensors.
ABSTRACT
STUDY QUESTION: How does ovarian stimulation in an oocyte donor affect the IVF cycle and obstetric outcomes in recipients? SUMMARY ANSWER: Higher donor oocyte yields may affect the proportion of usable embryos but do not affect live birth delivery rate or obstetric outcomes in oocyte recipients. WHAT IS KNOWN ALREADY: In autologous oocyte fresh IVF cycles, the highest live birth delivery rates occur when ~15-25 oocytes are retrieved, with a decline thereafter, perhaps due to the hormone milieu, with super-physiologic estrogen levels. There are scant data in donor oocyte cycles, wherein the oocyte environment is separated from the uterine environment. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study from 2008 to 2015 of 350 oocyte donors who underwent a total of 553 ovarian stimulations and oocyte retrievals. The oocytes were vitrified and then distributed to 989 recipients who had 1745 embryo transfers. The primary outcome was live birth delivery rate, defined as the number of deliveries that resulted in at least one live birth per embryo transfer cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included oocyte donors and recipients at a donor oocyte bank, in collaboration with an academic reproductive endocrinology division. Donors with polycystic ovary syndrome and recipients who used gestational carriers were excluded. The donors all underwent conventional ovarian stimulation using antagonist protocols. None of the embryos underwent pre-implantation genetic testing. The average (mean) number of embryos transferred to recipients was 1.4 (range 1-3). MAIN RESULTS AND THE ROLE OF CHANCE: Per ovarian stimulation cycle, the median number of oocytes retrieved was 30 (range: 9-95). Among the 1745 embryo transfer cycles, 856 of the cycles resulted in a live birth (49.1%). There were no associations between donor oocyte yield and probability of live birth, adjusting for donor age, BMI, race/ethnicity and retrieval year. The results were similar when analyzing by mature oocytes. Although donors with more oocytes retrieved had a higher number of developed embryos overall, there was a relatively lower percentage of usable embryos per oocyte warmed following fertilization and culture. In our model for the average donor in the data set, holding all variables constant, for each additional five oocytes retrieved, there was a 4% (95% CI 1%, 7%) lower odds of fertilization and 5% (95% CI 2%, 7%) lower odds of having a usable embryo per oocyte warmed. There were no associations between donor oocyte yield and risk of preterm delivery (<37 weeks gestation) and low birthweight (<2500 g) among singleton infants. LIMITATIONS, REASONS FOR CAUTION: Ovarian stimulation was exclusively performed in oocyte donors. This was a retrospective study design, and we were therefore unable to ensure proportional exposure groups. These findings may not generalizable to older or less healthy women who may be vitrifying oocytes for planned fertility delay. There remain significant risks to aggressive ovarian stimulation, including ovarian hyperstimulation. In addition, long-term health outcomes of extreme ovarian stimulation are lacking. Lastly, we did not collect progesterone levels and are unable to evaluate the impact of rising progesterone on outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Live birth delivery rates remain high with varying amounts of oocytes retrieved in this donor oocyte model. In a vitrified oocyte bank setting, where oocytes are typically sent as a limited number cohort, recipients are not affected by oocyte yields. STUDY FUNDING/COMPETING INTEREST(S): Additional REDCap grant support at Emory was provided through UL1 TR000424. Dr. Audrey Gaskins was supported in part by a career development award from the NIEHS (R00ES026648).
Subject(s)
Fertilization in Vitro , Oocyte Retrieval , Birth Rate , Female , Humans , Infant, Newborn , Live Birth , Oocytes , Ovulation Induction , Pregnancy , Pregnancy Rate , Retrospective StudiesABSTRACT
The mesoscopic Stoner instability is an intriguing manifestation of symmetry breaking in isolated metallic quantum dots, underlined by the competition between single-particle energy and Heisenberg exchange interaction. Here we study this phenomenon in the presence of tunnel coupling to a reservoir. We analyze the spin susceptibility of electrons on the quantum dot for different values of couplings and temperature. Our results indicate the existence of a "quantum phase transition" at a critical value of the tunneling coupling, which is determined by the Stoner-enhanced exchange interaction. This quantum phase transition is a manifestation of the suppression of the Coleman-Weinberg mechanism of symmetry breaking, induced by coupling to the reservoir.
ABSTRACT
BACKGROUND: Individuals with intellectual disabilities (ID) are at increased risk for depression and anxiety disorders; however, there is a paucity of research that pertains to associative factors for these mental health disorders in this population. The objective of this investigation was to determine factors associated with depression and anxiety problems in children with ID. METHODS: Children 6-17 years with ID (n = 423; 63% male) from the 2016 National Survey of Children's Health were included in this cross-sectional study. Outcome measures included depression and anxiety problems. Predictor variables included sociodemographics, ID severity, co-morbid conditions (autism spectrum disorders, epilepsy, cerebral palsy, Down syndrome and attention-deficit/hyperactivity disorder), physical factors (i.e. physical activity, sleep duration and pain) and social factors (e.g. participation in activities and bully victimisation). Multivariable logistic regression was performed to determine the association between all factors and depression and/or anxiety problems among children with ID. RESULTS: The prevalence of depression and/or anxiety problems was 35.4%. After adjusting for sociodemographics, Hispanic race was associated with lower odds [odds ratio (OR), 0.3; 95% confidence interval (CI), 0.1-0.8] of depression and/or anxiety problems. After adjusting for race, co-morbid conditions, and physical and social factors, autism spectrum disorders (OR, 4.4; 95% CI, 1.1-10.1), Down syndrome (OR, 0.2; 95% CI, 0.1-0.8), attention-deficit/hyperactivity disorder (OR, 5.9; 95% CI, 2.5-14.3), pain (OR, 7.0; 95% CI, 2.9-17.1) and bully victimisation (OR 2.3; 95% CI, 1.0-5.3) were each associated with depression and/or anxiety problems. CONCLUSIONS: The present study identified both treatable and modifiable, as well as unmodifiable, factors associated with depression and/or anxiety problems in children with ID.
Subject(s)
Anxiety/epidemiology , Attention Deficit Disorder with Hyperactivity/epidemiology , Autism Spectrum Disorder/epidemiology , Crime Victims/statistics & numerical data , Depression/epidemiology , Intellectual Disability/epidemiology , Pain/epidemiology , Adolescent , Bullying/statistics & numerical data , Child , Comorbidity , Cross-Sectional Studies , Down Syndrome/epidemiology , Female , Health Surveys , Humans , Male , United States/epidemiologyABSTRACT
The attractive plasmonic force between two metallic walls due to electromagnetic wave in the slit has been studied earlier for parallel plates and normal incidence. In present paper the effects of imperfectly adjusted plates and laser beam are analyzed. The change of force for non-parallel plates is shown to be of the first order in angle when the wedge is oriented along wave propagation and of the second order for the transverse case. Beam inclination decreases the force due to an antisymmetric mode excited in the slit.
ABSTRACT
An iterative method for computing the channel capacity of both discrete and continuous input, continuous output channels is proposed. The efficiency of new method is demonstrated in comparison with the classical Blahut - Arimoto algorithm for several known channels. Moreover, we also present a hybrid method combining advantages of both the Blahut - Arimoto algorithm and our iterative approach. The new method is especially efficient for the channels with a priory unknown discrete input alphabet.
ABSTRACT
Surveillance endoscopy of non-dysplastic Barrett's esophagus (NDBE) that fails to detect intestinal metaplasia (IM), or negative surveillance, is known to occur in clinical practice, although the frequency and possible outcomes in a large cohort in clinical practice is not well described. The goals of this study were to define frequency in which negative surveillance occurs and endoscopic outcomes in a screening cohort of short segment NDBE. A retrospective cohort (n = 184) of patients newly diagnosed with short segment NDBE at an outpatient academic tertiary care center between 2003 and 2011 were reviewed. Only those with one or more surveillance endoscopies were included to define a frequency of negative surveillance. Included patients were further assessed if they had two or more surveillance endoscopies and were classified into groups as sampling error or negative IM on consecutive surveillances based on the results of their surveillance endoscopies. The frequency of a negative surveillance endoscopy in all short-segment NDBE patients was 19.66% (92 endoscopic exams were negative for IM of 468 total surveillance exams). A negative surveillance endoscopy occurred in 40.76% (n = 75) patients. Sampling error occurred in 44.12% and negative IM on consecutive surveillance endoscopies in 55.88% of those with ≥ 2 surveillance endoscopies and an initially negative surveillance exam. The frequency of negative IM on consecutive surveillances was 19.00% of all patients who had two surveillance endoscopies. When the index diagnostic Barrett's esophagus segment length was < 1 cm, 32.14% (18/56) of all patients (with ≥ 2 surveillance endoscopies) had negative IM on consecutive surveillance endoscopies. Negative surveillance occurs frequently in short-segment NDBE. When an initial negative surveillance endoscopy occurs, it may be due to either a sampling error or lack of detectable IM on surveillance exam. When a <1 cm segment of NDBE is diagnosed, a significant proportion of patients may go on to have continuously undetected IM on consecutive surveillance endoscopic exams without intervention.
Subject(s)
Barrett Esophagus/pathology , Diagnostic Errors/statistics & numerical data , Early Detection of Cancer/statistics & numerical data , Esophagoscopy/statistics & numerical data , Intestines/pathology , Population Surveillance/methods , Adenocarcinoma/diagnosis , Adenocarcinoma/etiology , Aged , Barrett Esophagus/complications , Biopsy/statistics & numerical data , Early Detection of Cancer/methods , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/etiology , Female , Humans , Male , Metaplasia/diagnosis , Metaplasia/etiology , Middle Aged , Retrospective Studies , Stomach/pathologyABSTRACT
The onset of menopause and accompanying changes to ovarian hormones often precedes endothelial dysfunction in women. In particular, accelerated impairments in macrovascular and microvascular function coincide with the loss of estrogen, as does impaired endothelial responses to ischemia-reperfusion (IR) injury. In healthy, early postmenopausal women (n = 12; 3.9 ± 1.5 years since menopause) we tested the hypothesis that acute dietary nitrate (NO3-) supplementation would improve endothelial function and attenuate the magnitude of endothelial dysfunction following whole-arm IR in comparison with placebo. In this randomized, double-blind, placebo-controlled, crossover study we tested participants before and after NO3--rich (BRnitrate) and NO3--depleted (BRplacebo) beetroot juice (BR) consumption, as well as following IR injury, and 15 min after IR to assess recovery. Analyses with repeated-measures general linear models revealed a condition × time interaction for brachial artery flow-mediated dilation (FMD; P = 0.04), and no interaction effect was found for the near-infrared spectroscopy-derived reperfusion slope (P = 0.86). Follow-up analysis showed a significant decline in FMD following IR injury with BRplacebo in comparison with all other timepoints (all, P < 0.05), while this decline was not present with BRnitrate (all, P > 0.05). Our findings demonstrate that a single dose of dietary NO3- minimizes IR-induced macrovascular endothelial dysfunction in healthy, early postmenopausal women, but does not improve resting macrovascular and microvascular function. Trial registration number: NCT03644472. Novelty: In healthy, early postmenopausal women, a single dose of NO3--rich BR can protect against IR-induced endothelial dysfunction. This protection may be due to nitric oxide bioactivity during IR rather than improved endothelial function prior to the IR protocol per se.
Subject(s)
Nitrates , Reperfusion Injury , Cross-Over Studies , Dietary Supplements , Double-Blind Method , Endothelium, Vascular/physiology , Female , Humans , Nitric Oxide/pharmacology , Postmenopause , Reperfusion Injury/prevention & controlABSTRACT
Membrane proteins constitute > 30% of the proteins in an average cell, and yet the number of currently known structures of unique membrane proteins is < 300. To develop new concepts for membrane protein structure determination, we have explored the serial nanocrystallography method, in which fully hydrated protein nanocrystals are delivered to an x-ray beam within a liquid jet at room temperature. As a model system, we have collected x-ray powder diffraction data from the integral membrane protein Photosystem I, which consists of 36 subunits and 381 cofactors. Data were collected from crystals ranging in size from 100 nm to 2 µm. The results demonstrate that there are membrane protein crystals that contain < 100 unit cells (200 total molecules) and that 3D crystals of membrane proteins, which contain < 200 molecules, may be suitable for structural investigation. Serial nanocrystallography overcomes the problem of x-ray damage, which is currently one of the major limitations for x-ray structure determination of small crystals. By combining serial nanocrystallography with x-ray free-electron laser sources in the future, it may be possible to produce molecular-resolution electron-density maps using membrane protein crystals that contain only a few hundred or thousand unit cells.
Subject(s)
Cyanobacteria/chemistry , Nanoparticles/chemistry , Photosystem I Protein Complex/chemistry , X-Ray Diffraction , PowdersABSTRACT
We report on the first experimental ab initio reconstruction of an image of a single particle from fluctuations in the scattering from an ensemble of copies, randomly oriented about an axis. The method is applicable to identical particles frozen in space or time (as by snapshot diffraction from an x-ray free electron laser). These fluctuations enhance information obtainable from an experiment such as conventional small angle x-ray scattering.
ABSTRACT
Mitogen-activated murine T lymphocytes or T cell hybridomas produce an activity (megakaryocyte [Mk] potentiator activity) that enhances the in vitro growth and development of Mk colonies. This activity was found in optimal concentrations (2.5%) in T cell hybridoma-conditioned medium, and was also produced by feeder layers of concanavalin A-activated T cells. A subpopulation of murine Mk progenitor cells (colony-forming units; CFU-Mk) bears the Ia antigen. Separate experiments indicated that T cell products stimulate CFU-Mk by increasing their basal levels of Ia expression as well as the frequency of cells actively synthesizing DNA. The hypothesis that the expression of this antigen was related to the cell cycle status of these progenitor cells was confirmed in studies that indicated that ablation of actively cycling cells in vivo abrogated the cytotoxic effects of anti-Ia monoclonal antibodies. The interdependence of T cell lymphokine regulation of both Ia expression and cell cycle status was also seen in in vitro experiments in which Ia+ progenitor cells were eliminated by complement-dependent cytotoxicity. The removal of Ia+ cells prevented 5-hydroxyurea-mediated inhibition of cells in S phase. We hypothesize that immune modulation of megakaryocytopoiesis occurs via soluble T cell products that augment Mk differentiation. Further, the mechanism of immune recognition/modulation may occur via Ia antigens present on the surface of these progenitor cells.
Subject(s)
Hematopoiesis , Histocompatibility Antigens Class II/biosynthesis , Megakaryocytes/immunology , T-Lymphocytes/metabolism , Animals , Cell Cycle , Colony-Forming Units Assay , Concanavalin A/pharmacology , Culture Media , Growth Substances/biosynthesis , Growth Substances/physiology , Hematopoiesis/drug effects , Hematopoietic Cell Growth Factors , Hybridomas/metabolism , Interferon-gamma/pharmacology , Lymphocyte Activation , Male , Megakaryocytes/cytology , Mice , Mice, Inbred C57BL , Recombinant Proteins , T-Lymphocytes/immunologyABSTRACT
Mice with a targeted disruption of the interferon gamma receptor gene (IFN-gamma R0/0 mice) and control wild-type mice were inoculated with the Bacillus Calmette-Guérin (BCG) strain of Mycobacterium bovis. BCG infection was not lethal for wild-type mice whereas all IFN-gamma R0/0 mice died approximately 7-9 wk after inoculation. Histological examination at 2 and 6 wk after BCG inoculation showed that livers of IFN-gamma R0/0 mice had higher numbers of acid-fast bacteria than wild-type mice, especially at 6 wk. In parallel, the livers of IFN-gamma R0/0 mice showed a reduction in the formation of characteristic granulomas at 2 wk after inoculation. Injection of lipopolysaccharide (LPS) 2 wk after BCG inoculation was significantly less lethal for IFN-gamma R0/0 mice than for wild-type mice. Reduced lethality of LPS correlated with a drastically reduced production of tumor necrosis factor alpha (TNF-alpha) in the IFN-gamma R0/0 mice. Interleukin 1 alpha (IL-1 alpha) and IL-6 levels in the serum were also significantly reduced in the IFN-gamma R0/0 mice after BCG infection and LPS challenge. The greatly reduced capacity of BCG-infected IFN-gamma R0/0 mice to produce TNF-alpha may be an important factor in their inability to resist BCG infection. These results show that the presence of a functional IFN-gamma receptor is essential for the recovery of mice from BCG infection, and that IFN-gamma is a key element in the complex process whereby BCG infection leads to the sensitization to endotoxin.
Subject(s)
Lipopolysaccharides/pharmacology , Mycobacterium bovis/immunology , Receptors, Interferon/physiology , Tuberculosis/immunology , Animals , Cytokines/biosynthesis , Endotoxins/toxicity , Granuloma/microbiology , Immunity, Innate , Liver Diseases/microbiology , Liver Diseases/pathology , Mice , Mice, Inbred C57BL , Receptors, Interferon/genetics , Tuberculosis/mortality , Tuberculosis/pathology , Tumor Necrosis Factor-alpha/biosynthesis , Interferon gamma ReceptorABSTRACT
OBJECTIVE: To evaluate the efficacy, safety and tolerability of taranabant in obese and overweight patients. DESIGN: Double-blind, randomized, placebo-controlled study. SUBJECTS: Patients were >or=18 years old, with body mass index of 27-43 kg m(-2), and 51% with metabolic syndrome (MS) randomized to placebo (N=417) or taranabant 2 mg (N=414), 4 mg (N=415) or 6 mg (N=1256) for 104 weeks. MEASUREMENTS: Key efficacy measurements included body weight, waist circumference (WC), lipid and glycemic end points. RESULTS: On the basis of risk/benefit assessments, the 6-mg dose was discontinued during year 1 (patients on 6 mg were down-dosed to 2 mg or placebo) and the 4-mg dose was discontinued during year 2 (patients on 4 mg were down-dosed to 2 mg). Changes from baseline in body weight at week 52 (all-patients-treated population, last observation carried forward analysis) were -2.6, -6.6 and -8.1 kg, respectively, for placebo and taranabant 2 and 4 mg (both doses P<0.001 vs placebo). For patients who completed year 1, changes from baseline in body weight at week 104 were -1.4, -6.4 and -7.6 kg for placebo and taranabant 2 and 4 mg, respectively (both doses P<0.001 vs placebo). The proportions of patients at weeks 52 and 104 who lost at least 5 and 10% of their baseline body weight were significantly higher and the proportions of patients who met criteria for MS were significantly lower for taranabant 2 and 4 mg vs placebo. The incidence of adverse experiences classified in the gastrointestinal, nervous, psychiatric, cutaneous and vascular organ systems were generally observed to be dose related with taranabant vs placebo. CONCLUSION: Taranabant at the 2- and 4-mg dose was effective in achieving clinically significant weight loss over 2 years and was associated with dose-related increases in adverse experiences. On the basis of these and other data, an assessment was made that the overall safety and efficacy profile of taranabant did not support its further development for the treatment of obesity.
Subject(s)
Amides/administration & dosage , Anti-Obesity Agents/administration & dosage , Body Weight/drug effects , Metabolic Syndrome/drug therapy , Obesity/drug therapy , Pyridines/administration & dosage , Adult , Aged , Aged, 80 and over , Amides/adverse effects , Anti-Obesity Agents/adverse effects , Body Mass Index , Body Weight/physiology , Diet, Reducing , Double-Blind Method , Female , Humans , Male , Metabolic Syndrome/physiopathology , Middle Aged , Obesity/physiopathology , Pyridines/adverse effects , Receptor, Cannabinoid, CB1/agonists , Risk Assessment , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: To investigate the reported association between exaggerated adrenarche (EA) and reduced foetal growth and to identify possible risk factors for future morbidity in Scottish children with clinical features of EA. DESIGN: Three-year prospective study. MEASUREMENTS: Auxology, blood pressure (BP), biochemical analysis of blood and urine, pelvic ultrasound in girls. RESULTS: Fifty-two patients were recruited of whom one girl had nonclassical congenital adrenal hyperplasia (17-OHP 17 nmol/l) and one had insufficient blood for analysis. The final cohort comprised 42 girls of mean (SD) age 7.7 (0.99) and eight boys of 8.8 (0.67) years. Mean (SD) birth weight was 3.27 (0.49) and 3.10 (0.76) kg in girls and boys respectively. Height/weight SDS were 1.13/1.69 in girls and 1.69/1.88 in boys. Mean systolic/diastolic BP was 107.8/60.4 (50th-75th centile) in girls and 115.5/63.9 (75th-91st centile) in boys. Uterine and ovarian development was prepubertal. Median serum dehydroepiandrosterone sulphate (DHEAS) was 2.1 and 4.1 mumol/l, androstenedione 3.1 and 3.8 nmol/l in girls and boys respectively, with DHEAS within the reference range/undetectable in 18/2 and androstenedione in 12/6 patients. Fasting insulin was 9.0 and 15.0 mU/l in girls and boys respectively, with concomitant low normal SHBG. Anti-Mullerian hormone (AMH) was 15.7 pmol/l in 27 girls, compared with 5.0 pmol/l in normal girls aged 5-8 years. CONCLUSIONS: Our Scottish EA cohort showed female predominance, no evidence of reduced foetal growth, a tendency to overweight with commensurate mild hyperinsulinaemia and modest elevation of serum androgens in some patients. We have found raised AMH levels in the girls, indicating advanced ovarian follicular development.
Subject(s)
Adrenarche/physiology , Androgens/blood , Anti-Mullerian Hormone/blood , Birth Weight , Child , Female , Humans , Hyperinsulinism/etiology , Infant, Newborn , Male , Ovarian Follicle/growth & development , Pelvis/diagnostic imaging , Prospective Studies , UltrasonographyABSTRACT
AIM: To evaluate the efficacy and safety of taranabant in overweight and obese patients with type 2 diabetes mellitus (T2DM). METHODS: This was a multicenter, double-blind, randomized, placebo-controlled study in overweight and obese patients with T2DM (ages > or = 18 and < or = 75 years) with a BMI > or = 27 kg/m(2) and < or = 43 kg/m(2) and HbA1c > or =7.0 and < or = 10.0%, who were either not on an antihyperglycaemic agent or on a stable dose of metformin (> or = 1500 mg/day). After a 2-week placebo run-in, patients were randomized to placebo (N = 156) or taranabant 0.5-mg (N = 155), 1-mg (N = 157), or 2-mg (N = 155) once daily for 52 weeks. Primary efficacy endpoints were changes from baseline in body weight (BW) and HbA1c at Week 36, with results at Week 52 being key secondary endpoints. RESULTS: In the all-patients-treated population, using a last-observation-carried-forward analysis, reductions in BW were -2.5, -3.7, -4.5 and -5.1 kg at Week 36 and -2.4, -4.0, -4.6 and -5.3 kg at Week 52 in the placebo, 0.5-, 1- and 2-mg groups, respectively (all doses significant vs. placebo at both time points). The proportion of patients who lost > or = 5 and > or = 10% of their baseline BW was significantly greater in the 1- and 2-mg groups vs. placebo at Week 36 and all taranabant groups vs. placebo at Week 52. Reductions in HbA1c were -0.40, -0.47, -0.68 and -0.71% at Week 36 and -0.30, -0.43, -0.65 and -0.64% at Week 52, in the placebo, 0.5-, 1- and 2-mg groups, respectively (1- and 2-mg doses significant vs. placebo at both time points). After 52 weeks, the incidences of adverse experiences classified in the gastrointestinal (diarrhoea, nausea, vomiting), nervous system-related (dizziness, sensory-related), and psychiatric (irritability, depression-related) organ systems were numerically higher or statistically significantly higher in all taranabant groups compared with the placebo group. CONCLUSIONS: After 36 and 52 weeks, treatment with taranabant at the 1- and 2-mg doses led to clinically significant weight loss and improvement in glycaemic parameters in overweight and obese patients with T2DM that was associated with dose-related increases in adverse experiences. Based on these data and data from other Phase III clinical studies, it was determined that the overall safety and efficacy profile of taranabant did not support further development for the treatment of obesity.
Subject(s)
Amides/administration & dosage , Anti-Obesity Agents/administration & dosage , Diabetes Mellitus, Type 2/drug therapy , Obesity/drug therapy , Pyridines/administration & dosage , Receptor, Cannabinoid, CB1/agonists , Adolescent , Adult , Aged , Amides/adverse effects , Anti-Obesity Agents/adverse effects , Body Mass Index , Diabetes Mellitus, Type 2/complications , Diet, Reducing , Double-Blind Method , Female , Humans , Male , Middle Aged , Obesity/complications , Obesity/diet therapy , Pyridines/adverse effects , Weight Loss/drug effects , Young AdultABSTRACT
BACKGROUND: Hyponatraemia is the commonest electrolyte disorder in the elderly. Data on severe hyponatraemia and the prevalence of cerebral salt wasting syndrome (CSWS) in elderly hospitalized patients are lacking. We studied the incidence, frequency of various aetiologies, outcome and the possible role of CSWS in severe hyponatraemia in elderly medical patients. METHODS: A prospective, observational, non-interventional study conducted over a 5-month period in medical wards. Eighty-six patients aged over 65 years with serum sodium levels < or =125 mEq/L were included. All patients were examined by one of the authors, who also evaluated potential contributing factors. Demographic, clinical and outcome data were extracted from the medical records. RESULTS: The mean age of the patients was 82.1 + 8.7 years. The prevalence of hyponatraemia was 6.2% (8.1% women and 4.0% men (P < 0.001)). There was no increase in incidence of hyponatraemia with age. The leading cause of hyponatraemia was the syndrome of inappropriate antidiuretic hormone secretion (SIADH), whose aetiology could be determined in only 46% of cases. Aetiology was multifactorial in 51% of patients (1.7 aetiological factors per patient). All patients with thiazide-induced hyponatraemia had other contributing factors. Hyperglycaemia and hypoalbuminaemia were predictors of neurological manifestations of hyponatraemia. Overall in-hospital mortality was 19%. Only hypoalbuminaemia was found as an independent risk factor for death. In none of the patients was the hyponatraemia due to CSWS. CONCLUSION: Severe hyponatraemia in elderly hospitalized medical patients is more frequent in women and of multifactorial aetiology in 50% of cases. It is most commonly caused by SIADH; CSWS is an unlikely cause.
Subject(s)
Hospitalization/trends , Hyponatremia/epidemiology , Hyponatremia/etiology , Severity of Illness Index , Age Factors , Aged , Aged, 80 and over , Female , Heart Failure/complications , Heart Failure/epidemiology , Hospitals, Community/trends , Humans , Hyponatremia/therapy , Male , Prevalence , Prospective Studies , Sodium Chloride Symporter Inhibitors/adverse effects , Treatment OutcomeABSTRACT
The simultaneous removal of three to nine males from large social groups of Anthias squamipinnis led to close to a one-to-one replacement of the removed males by sex-reversing females. The females changed sex serially within each group with a mean interval between successive onset times of 1.9 days. The timing of sex change is thus not independent for each fish but is influenced by the events surrounding other sex reversals within the group.
ABSTRACT
An automatic procedure providing information about human systolic blood pressure at each successive heartbeat under routine laboratory conditions is described. Twenty normal male subjects were given feedback of their own systolic pressure, half operantly reinforced for increasing and half reinforced for decreasing their pressure. Significant differences in pressure were obtained in a single session. The apparatus and results suggest a possible approach to the treatment of essential hypertension.
Subject(s)
Blood Pressure , Conditioning, Operant , Reinforcement, Psychology , Adult , Analysis of Variance , Automation , Blood Pressure Determination/instrumentation , Clinical Trials as Topic , Electrocardiography , Feedback , Humans , Hypertension/therapy , Male , MethodsABSTRACT
Operant conditioning-feedback techniques were employed to lower systolic blood pressure in seven patients with essential hypertension. In five of the patients, meaningful decreases of systolic blood pressure were obtained in the laboratory, ranging from 16 to 34 millimeters of mercury. The therapeutic value of such techniques remains to be established.