Sensor Noise in LISA Pathfinder: In-Flight Performance of the Optical Test Mass Readout.

We report on the first subpicometer interferometer flown in space. It was part of ESA's Laser Interferometer Space Antenna (LISA) Pathfinder mission and performed the fundamental measurement of the positional and angular motion of two free-falling test masses. The interferometer worked immediately, stably, and reliably from switch on until the end of the mission with exceptionally low residual noise of 32.0_{-1.7}^{+2.4} fm/sqrt[Hz], significantly better than required. We present an upper limit for the sensor performance at millihertz frequencies and a model for the measured sensitivity above 200 mHz.

MCO: towards an ontology and unified vocabulary for a framework-based annotation of microbial growth conditions.

MOTIVATION: A major component in increasing our understanding of the biology of an organism is the mapping of its genotypic potential into its phenotypic expression profiles. This mapping is executed by the machinery of gene regulation, which is essentially studied by changes in growth conditions. Although many efforts have been made to systematize the annotation of experimental conditions in microbiology, the available annotations are not based on a consistent and controlled vocabulary, making difficult the identification of biologically meaningful comparisons of knowledge derived from different experiments or laboratories. RESULTS: We curated terms related to experimental conditions that affect gene expression in Escherichia coli K-12. Since this is the best-studied microorganism, the collected terms are the seed for the Microbial Conditions Ontology (MCO), a controlled and structured vocabulary that can be expanded to annotate microbial conditions in general. Moreover, we developed an annotation framework to describe experimental conditions, providing the foundation to identify regulatory networks that operate under particular conditions. AVAILABILITY AND IMPLEMENTATION: As far as we know, MCO is the first ontology for growth conditions of any bacterial organism, and it is available at http://regulondb.ccg.unam.mx and https://github.com/microbial-conditions-ontology. Furthermore, we will disseminate MCO throughout the Open Biological and Biomedical Ontology (OBO) Foundry in order to set a standard for the annotation of gene expression data. This will enable comparison of data from diverse data sources. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

LISA Pathfinder Performance Confirmed in an Open-Loop Configuration: Results from the Free-Fall Actuation Mode.

We report on the results of the LISA Pathfinder (LPF) free-fall mode experiment, in which the control force needed to compensate the quasistatic differential force acting on two test masses is applied intermittently as a series of "impulse" forces lasting a few seconds and separated by roughly 350 s periods of true free fall. This represents an alternative to the normal LPF mode of operation in which this balancing force is applied continuously, with the advantage that the acceleration noise during free fall is measured in the absence of the actuation force, thus eliminating associated noise and force calibration errors. The differential acceleration noise measurement presented here with the free-fall mode agrees with noise measured with the continuous actuation scheme, representing an important and independent confirmation of the LPF result. An additional measurement with larger actuation forces also shows that the technique can be used to eliminate actuation noise when this is a dominant factor.

Beyond the Required LISA Free-Fall Performance: New LISA Pathfinder Results down to 20 µHz.

In the months since the publication of the first results, the noise performance of LISA Pathfinder has improved because of reduced Brownian noise due to the continued decrease in pressure around the test masses, from a better correction of noninertial effects, and from a better calibration of the electrostatic force actuation. In addition, the availability of numerous long noise measurement runs, during which no perturbation is purposely applied to the test masses, has allowed the measurement of noise with good statistics down to 20 µHz. The Letter presents the measured differential acceleration noise figure, which is at (1.74±0.05) fm s^{-2}/sqrt[Hz] above 2 mHz and (6±1)×10 fm s^{-2}/sqrt[Hz] at 20 µHz, and discusses the physical sources for the measured noise. This performance provides an experimental benchmark demonstrating the ability to realize the low-frequency science potential of the LISA mission, recently selected by the European Space Agency.

Charge-Induced Force Noise on Free-Falling Test Masses: Results from LISA Pathfinder.

We report on electrostatic measurements made on board the European Space Agency mission LISA Pathfinder. Detailed measurements of the charge-induced electrostatic forces exerted on free-falling test masses (TMs) inside the capacitive gravitational reference sensor are the first made in a relevant environment for a space-based gravitational wave detector. Employing a combination of charge control and electric-field compensation, we show that the level of charge-induced acceleration noise on a single TM can be maintained at a level close to 1.0 fm s^{-2} Hz^{-1/2} across the 0.1-100 mHz frequency band that is crucial to an observatory such as the Laser Interferometer Space Antenna (LISA). Using dedicated measurements that detect these effects in the differential acceleration between the two test masses, we resolve the stochastic nature of the TM charge buildup due to interplanetary cosmic rays and the TM charge-to-force coupling through stray electric fields in the sensor. All our measurements are in good agreement with predictions based on a relatively simple electrostatic model of the LISA Pathfinder instrument.

High neutrophil to lymphocyte ratio measured before starting ipilimumab treatment is associated with reduced overall survival in patients with melanoma.

BACKGROUND: There is an unmet need to identify markers predictive of response to ipilimumab in patients with melanoma because the number of responders to ipilimumab is low and its cost is very high. An increase in absolute lymphocyte count (ALC) or low neutrophil/lymphocyte ratio (NLR) just before the third infusion has been reported to be associated with better overall survival (OS). OBJECTIVES: Our aim was to determine whether NLR measured before the first infusion was associated with OS. PATIENTS AND METHODS: Data were collected on a consecutive series of 58 patients treated with ipilimumab in four hospitals, including 51 at stage M1c and four at stage M1b. The influences of the NLR and other factors such as lactate dehydrogenase (LDH), performance status, ALC, absolute neutrophil count (ANC) and corticosteroids on survival were studied. We also assessed this association with NLR categorized as a binary variable. The cut-off value for the NLR was determined with time-dependent receiver operating characteristic (ROC) analysis. Univariate and multivariate analyses were performed using Cox regression models. RESULTS: High NLR (≥) 4, high ANC LDH levels (>2), performance status ≥2, symptomatic brain metastases, and corticosteroids before week 1 were associated with poorer survival on univariate analysis. Using multivariate analysis, a significant association between high NLR (continuous variable) and poorer survival was demonstrated and remained significant after adjustment on potential confounders [hazard ratio (HR) = 1·21, 95% confidence interval (CI) 1·07-1·36]. NLR ≥4 was an independent prognostic factor (HR = 2·2, 95% CI 1·01-4·78). Intake of corticosteroids before week 1 was not an independent prognostic factor (HR = 1·28, 95% CI 0·54-3·06). CONCLUSIONS: High NLR (≥4) before initiating ipilimumab treatment in patients with metastatic melanoma is an independent prognostic indicator of poor survival.

Cardiac adverse effects of naloxone-precipitated morphine withdrawal on right ventricle: role of corticotropin-releasing factor (CRF) 1 receptor.

Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic-pituitary-adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts.

Do epoch lengths affect adolescents' compliance with physical activity guidelines?

AIM: This study examined the effect of different epoch lengths (from 3 to 60 s) on (a) moderate to vigorous physical activity (MVPA), (b) 10 minutes bouts of MVPA and (c) compliance with World Health Organization (WHO) guidelines, as measured with an ActiGraph accelerometer. METHODS: A sample of 401 adolescents (14.48±0.69 years) wore a GT3X accelerometer to measure physical activity (PA) for 7 consecutive days. Data, originally collected in 1-s epoch(s), were then reintegrated into epochs of 3-, 5-, 10-, 15-, 30-, 45- and 60-s. RESULTS: The results showed a significant epoch effect (P=0.000) for time spent in MVPA, 10-min bouts of MVPA and the extent of compliance with guidelines percentage of compliance of guidelines. Bland-Altman analysis showed good agreement between 5- and 10-, 5- and 15-, and 10- and 15-s data, both for MVPA and 10-min bouts of MVPA. CONCLUSION: Epidemiological studies should take into account the sampling interval to offer accurate conclusions with regard to levels of MVPA and the extent to which adolescents comply with guidelines. Shorter epochs, such as 5-, 10- or 15-s are proposed for comparative studies carried out with adolescents in this area.

Lymphoproliferative response to the 30-kDa protein and a crude lysate from Salmonella typhimurium in patients with ankylosing spondylitis.

OBJECTIVES: To determine the lymphoproliferative response to the 30-kDa protein (p30) of Salmonella typhimurium in patients with ankylosing spondylitis (AS). METHOD: Lymphoproliferative response was determined in peripheral blood mononuclear cells (PBMCs) from 30 patients with AS and 40 healthy subjects. Cells were cultured with concanavalin A (Con A), a crude lysate of S. typhimurium (StCL), or p30. Lymphoproliferation was measured by the MTT assay. RESULTS: Our data show that the mitogenic response to Con A was similar in both groups studied; however, the lymphoproliferative response to StCL and p30 was statistically higher in AS patients than in healthy subjects. CONCLUSIONS: Our data strongly suggest that S. typhimurium, and particularly p30, are associated with AS.

[A rare side effect of mesotherapy: Nicolau syndrome]. / Un effet indésirable rare de la mésothérapie : la dermite de Nicolau.

BACKGROUND: Nicolau's livedoid dermatitis is associated with drug-induced embolism in the cutaneous arterial bed, generally as a result of accidental intra-arterial injection. Herein, we report a case that is somewhat surprising because of its late onset following mesotherapy injections. CASE REPORT: A 53-year-old man, with a history solely of tendinopathy for which he underwent mesotherapy sessions, consulted for livedoid lesions of the front of the knee with central necrosis. History-taking revealed a final course of mesotherapy three weeks earlier for patellar tendinitis below the left kneecap; intradermal injection of procaine and piroxicam had been unusually and intensely painful. The remainder of the clinical examination revealed additional livedoid lesions on the outside of the left ankle as well as purpuric lesions on the pads of the toes on the left foot. Laboratory tests revealed nothing of note. Skin biopsies of the livedoid circumference of the lesion showed arteriolar emboli of an amorphous material within the dermis obliterating the arteriolar lumen. The clinical appearance of skin lesions after mesotherapy led us to a diagnosis of Nicolau livedoid dermatitis. DISCUSSION: Nicolau dermatitis is a rare skin complication described as occurring mainly as a result of intramuscular injections. The reported case is special because it comprises Nicolau dermatitis arising out of a session of mesotherapy employing an intradermal injection. However, there are only very few cases in which subcutaneous injections have induced Nicolau dermatitis. The pathophysiology is not well known, but several mechanisms are involved: arterial ischaemia by vasospasm or thrombosis. In this case, the semiotic appearance of the lesions and histological analysis militate in favour of accidental injection of a skin product into an arteriole, resulting in obliteration of the latter. Mesotherapy can induce Nicolau dermatitis.

7-Nitroindazole reduces L-DOPA-induced dyskinesias in non-human Parkinsonian primate.

Nitric oxide (NO) plays a pivotal role in integrating dopamine transmission in the basal ganglia and has been implicated in the pathogenesis of Parkinson disease (PD). The objective of this study was to ascertain whether the NO synthase inhibitor, 7-nitroindazole (7-NI), is able to reduce L-DOPA-induced dyskinesias (LIDs) in a non-human primate model of PD chronically intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Six Parkinsonian macaques were treated daily with L-DOPA for 3-4 months until they developed LIDs. Three animals were then co-treated with a single dose of 7-NI administered 45 min before each L-DOPA treatment. Dyskinetic MPTP-treated monkeys showed a significant decrease in LIDs compared with their scores without 7-NI treatment (p < 0.05). The anti-Parkinsonian effect of L-DOPA was similar in all three monkeys with and without 7-NI co-treatment. This improvement was significant with respect to the intensity and duration of LIDs while the beneficial effect of L-DOPA treatment was maintained and could represent a promising therapy to improve the quality of life of PD patients.

Acceptable variability in external quality assessment programmes for basic semen analysis.

BACKGROUND: External quality assessment is essential in modern andrology laboratories. To assess the proficiency of laboratories participating in an external quality assessment programme (EQAP), limits for acceptable variability must be determined. Limits currently specified largely depend on criteria set by the organizers of individual EQAP schemes. The objective of this study was to evaluate the different criteria described in ISO 13528: 2005 for calculating acceptable variability in EQAP when applied to basic semen analysis parameters. METHODS AND RESULTS: The data used in this study were the means and standard deviations obtained for independent samples from two EQAPs, one national (Spanish) and one international (European). The acceptable variability according to ISO 13528: 2005 was calculated using four types of criteria: (i) ± 3 standard deviations of the results of all participating laboratories; (ii) ± 3 standard deviations of the results of expert laboratories; (iii) quality specifications based on biological variability, state-of-the-art and clinicians' opinions and (iv) the same quality specifications adjusted for the uncertainty of the assigned value. The first two strategies resulted in very wide ranges of acceptable variability. Conversely, the strategy based only on quality specifications resulted in very narrow ranges. For the fourth strategy, acceptable ranges were intermediate between the results produced with the other strategies. The third and fourth strategies did not produce observable differences in acceptable ranges when the model used for calculating the specifications of analytical quality was changed. CONCLUSIONS: It is essential that EQAPs for semen parameters should determine the ranges for acceptable variability in results. Moreover, these ranges must be clinically useful, i.e. the variability should have a minimal negative impact on clinical decisions. The exact definition of 'expert laboratory' is more important than the model chosen for estimating analytical quality specifications in an EQAP for semen parameters in basic semen analysis.

[Comorbidities in patients hospitalized due to chronic obstructive pulmonary disease. A comparative analysis of the ECCO and ESMI studies]. / Comorbilidades en pacientes hospitalizados por enfermedad pulmonar obstructiva crónica. Análisis comparativo de los estudios ECCO y ESMI.

BACKGROUNDS AND OBJECTIVES: The presence of associated diseases is very frequent in patients hospitalized due to exacerbation of COPD. We have studied the comorbidities of patients admitted due to the disease in the Spanish Internal Medicine Services and we have evaluated the variations in regards to a previous study (ECCO study) performed two years earlier. PATIENTS AND METHODS: A cross-sectional, multicenter and cohort study was performed. Patients hospitalized due to exacerbation of COPD in Spanish Internal Medicine Services were enrolled. All the patients were studied for the presence of comorbidity using the Charlson index and a questionnaire with relevant conditions not included in this index. Furthermore, spirometric data were collected on the duration of the disease or home treatment, among other variables. RESULTS: A total of 1004 patients (398 in the ECCO study and 606 in the ESMI study) were studied. Of these, 89.4% were males, with mean age of 73 years (SD: 9.5 years). The patients of the ESMI study obtain higher scores on the Charlson index (3.04 vs. 2.71; P<0.01), and had a greater prevalence of ischemic heart disease (17 vs. 22.0%; P<0.05), heart failure (26.9 vs. 35.5%; P<.002), peripheral vascular disease (12.6 vs. 17.4%; P<.02), arterial hypertension (54.8 vs. 65.6%; P<.001), diabetes mellitus (29.4 vs. 37%; P<.02) and renal failure (6.5 vs. 16.8%; P<.0001). CONCLUSIONS: This study confirms the elevated prevalence of associated diseases in patients with COPD who are admitted to the Spanish Internal Medicine Services and the increase of comorbidities.

Barriers to adolescent girls' participation in physical activity defined by physical activity levels.

AIM: Perceived barriers were the single most powerful predictors of a change in health behaviours and the most consistent negative correlate of children's actual physical activity (PA). The purpose of this study was to compare the perceived barriers of physical activity in 714 adolescent girls defined by physical activity levels. METHODS: The final sample consisted of 714 adolescent, student girls. The age of these students ranged from 12 to 15 years, with a mean age of 13.5 ± 0.7 years. Perceived physical activity and perceived barriers to physical activity were measured using the Physical Self-Description Questionnaire and a Scale of Barriers that includes 17 units of barriers divided into two categories: intrapersonal barriers and environmental/contextual barriers. RESULTS: In our study, girls with a low activity level perceived a greater number of barriers than those with a high activity level, more specifically three intrapersonal barriers and two environmental/contextual barriers. Girls with a low activity level reported greater barriers to physical activity than high-active girls for these barriers: don't like physical activity (F=23.405, p=0.001), not good at physical activity and sports (F=24.160, p=0.001), I'm too lazy to do physical activity (F=8.415, P=0.001), it is not safe to do physical activity outdoors (F=11.39, P<0.001) and there is no-one to do physical activity with (F=15.22 P<0.001). CONCLUSION: This study shows the need to learn and effectively use time management strategies that emphasize prioritising and better scheduling of physical activities.

Physical activity patterns in normal-weight adolescents on week-days and week-ends.

AIM: This study aimed to assess the day-to-day variability of children's physical activity by accelerometer on week-days and week-end days, and to determine the proportion of children that comply with the established physical activity (PA) guidelines. METHODS: Physical activity was recorded every minute by uniaxial accelerometer in 104 normal-weight adolescent students (64 boys and 40 girls) for up to two different weeks (in winter and spring) and over seven consecutive days each week. We examined the difference in minutes for each gender and for the intensity of physical activity over the days of the week. The study took place in the north-east of Spain in 2009. RESULTS: Gender was found to produce the most significant results. Boys engaged in more moderate, vigorous and moderate to vigorous physical activity (MVPA) than girls. Children accumulated more physical activity on week-days than on week-end days. Adolescents' PA is mainly derived from their engagement in light activities. The majority of the adolescents did not reach the recommended ≥60 minutes of MVPA. CONCLUSION: This study suggests that Spanish adolescents engage in limited amounts of MVPA on week-days and week-ends, with activity levels differing according to sex and day of the week. Given that less activity is accumulated at the week-end, especially amongst girls, the out-of-school environment should be the focus for more activity.

[Combined hormonal contraception in cycles artificially extended]. / Anticoncepción con hormonales combinados en ciclos extendidos artificialmente.

OBJECTIVE: To compare the bleeding patterns, satisfaction and tolerability of 3 different contraceptive in an extended regimens in the service of Family Planning of the North Central Hospital of PEMEX. MATERIAL AND METHODS: Healthy, adult women with desire of contraception for one year (N 120) were randomly assigned to receive oral contraceptive drospirenone/ethinyl E2 (group1), the norelgestromin/ethinyl E2 transdermal patch (group 2) and vaginal ring etonogestrel/ ethinyl E2 (group 3) in an extended regimen (42 consecutive days, 1 hormone-free week). Study assessments were conducted at scheduled visits at the time of initial screening, at baseline after 1, 3, 6, and 12 months. Subjects recorded menstrual associated symptoms bleeding data and completed satisfaction questionnaires. Subjects and investigators provided overall assessments of the regimens. RESULTS: Extended use of 3 different contraceptive resulted in fewer bleeding days in every group (66.6%, 55% and 58.3% P 0.0024), and less mastalgia and menstrual pain. Subjects were highly satisfied with three regimens (93.3%, 96.6% and 91.6% P 0.00421). Although not mayor adverse events were reported with this regimen, there was an increase in spotting days; it decreased with each successive cycle of therapy. Efficacy and safety were similar to those reported for traditional cycle. CONCLUSION: Extended-contraceptive regimen delays menses and reduces bleeding, a profile that may be preferred by women who seek flexibility with their contraceptive method.

Analysis of the accuracy of actuation electronics in the laser interferometer space antenna pathfinder.

The Laser Interferometer Space Antenna Pathfinder (LPF) main observable, labeled Δg, is the differential force per unit mass acting on the two test masses under free fall conditions after the contribution of all non-gravitational forces has been compensated. At low frequencies, the differential force is compensated by an applied electrostatic actuation force, which then must be subtracted from the measured acceleration to obtain Δg. Any inaccuracy in the actuation force contaminates the residual acceleration. This study investigates the accuracy of the electrostatic actuation system and its impact on the LPF main observable. It is shown that the inaccuracy is mainly caused by the rounding errors in the waveform processing and also by the random error caused by the analog to digital converter random noise in the control loop. Both errors are one order of magnitude smaller than the resolution of the commanded voltages. We developed a simulator based on the LPF design to compute the close-to-reality actuation voltages and, consequently, the resulting actuation forces. The simulator is applied during post-processing the LPF data.

[Validation of MNA scale score as a nutritional risk factor in institutionalized geriatric patients with moderate and severe cognitive impairment]. / Validez de la escala MNA como factor de riesgo nutricional en pacientes geriátricos institucionalizados con deterioro cognitivo moderado y severo.

INTRODUCTION: comprehensive geriatric assessment includes examination of the nutritional status given the high prevalence of hyponutrition in this kind of patients, particularly in patients with associated cognitive impairment. Scales for screening the nutritional status include questions on self-perception difficult to answer by demented elder patients. OBJECTIVE: To study the specificity, the positive predictive value, and the sensitivity of the MNA scale to detect malnutrition in patients diagnosed with Alzheimer's disease with advanced cognitive impairment. MATERIAL AND METHODS: a population-based descriptive study with a sample of 52 patients older than 70 years, institutionalized, and with moderate-severe Alzheimer's disease was designed. The sensitivity, specificity, and positive predictive value of MNA scale were studied regarding the parameters on malnutrition of the American Institute of Nutrition (AIN). RESULTS: the sensitivity, specificity, and positive predictive values were 60%, 94.7%, and 93.8%, respectively. There was a significant correlation (p < 0.001) between the score obtained with the MNA Scale and the Tinneti's Risk of Fall Scale (r = 0.577), the Barthel's function (r = 0.742), the MCT cognitive assessment (r = 0.651), and creatinine levels (r = 0.402). More than 50% of the sample presented at least one malnutrition parameter altered. CONCLUSIONS: the MNA Scale presents lower sensitivity and specificity in these patients. Designing a nutritional assessment scale without subjective evaluations and only with objective parameters might improve its efficiency in institutionalized elderly patients with moderate-severe cognitive impairment.