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Small cell lung cancer (SCLC) is an aggressive neuroendocrine neoplasm with poor survival outcomes and little change to treatment standards over decades. SCLC is associated with heavy tobacco exposure and a high rate of somatic mutations in tumor cells, leading to hope that immune checkpoint inhibitors would dramatically reshape the treatment landscape of SCLC. Instead, immune checkpoint inhibitors have led to real but modest gains in outcomes, with only a small minority of patients deriving more durable benefit. Furthermore, biomarkers of ICI efficacy that have succeeded in other tumor types have not been validated in SCLC. However, recent research advances have suggested that epigenetic heterogeneity and plasticity play especially key roles in SCLC biology. Leveraging this emerging perspective, a new slate of candidate biomarkers of immune checkpoint inhibitor benefit have been described, and the novel treatment strategies combining rational epigenetic perturbation with immune checkpoint inhibitors are being developed. Finally, other immunotherapy strategies targeting SCLC-specific mechanisms are being tested. Together, these developments may lead to a second generation of much more efficacious immunotherapies in SCLC.

Chronic inflammation has been implicated in carcinogenesis, with increasing evidence of its role in lung cancer. We aimed to evaluate the role of genetic polymorphisms in inflammation-related genes in the risk for development of lung cancer.

The development of steel refining operations at ArcelorMittal FCWE for the production of ULS steels is reported. Several plants with different equipments produce grades with S <30 ppm, thus permitting to identify the most efficient process, from hot metal desulfurization to secondary metallurgy. For sites producing steels with S <30 ppm, four secondary metallurgy routes coexist in ArcelorMittal FCWE. The Vacuum Tank Degasser makes it possible to reach very low S and N contents simultaneously. To face the increase of the share of Ultra Low Sulfur products, it is necessary to further enhance the kinetics of desulfurization by steel - slag stirring at the atmospheric pressure.

Clogging of Continuous Casting nozzle has a detrimental effect on productivity and product quality; it also increases production costs and goes against security. Many factors contribute to the clogging phenomenon, including the detailed process parameters of continuous casting and secondary metallurgy.
Clogging can be effectively limited by Argon injection that is usually performed through the stopper rod. The nature and quality of the refractory equipment is another factor that must be considered carefully. The clogging mechanism has been clearly ascribed to the level and nature of non metallic inclusions, thus to the secondary metallurgy process.
Effective counter measures that have been successfully implemented in Arcelor to achieve long sequence casting are presented.

The aim of this study was to determine the impact of termination of pregnancy (TOP) on women's sexual well-being, the couple and contraceptive practice. In a prospective qualitative and quantitative study, 103 women undergoing induced abortion by vacuum aspiration were interviewed before the abortion and 6 months later. The interview was performed by means of a questionnaire including open and closed questions, and two psychological tests (Locke-Wallace and Horowitz). After TOP, the majority of women did not report changes in their sexual behavior and satisfaction. Eighteen per cent of women reported a decrease in sexual desire and 17% reported orgasmic disorders. About one-third of women described psychosomatic symptoms, but a minority were traumatized by the event. Ninety-eight per cent of the women were informed about, and had practiced, contraception in the past; 69% had actually used some kind of contraception during the menstrual cycle that had resulted in pregnancy (31% had had unprotected intercourse). Six months later, 83% practiced contraception, and only 17% did not. Fourteen out of 84 couples separated after TOP (one in six). Six months after TOP, the large majority of women interviewed seemed able to cope with TOP. A minority presented some persisting sexual dysfunction and/or some psychosomatic symptoms.

Monitoring of non-invasive ventilation (NIV) in a non-intensive care unit (non-ICU) setting requires a method of evaluating nocturnal P aCO₂, such as transcutaneous CO₂monitoring (Tc P CO₂). However, changing the probe site after 4 h and recalibrating (as recommended) is time-consuming and impractical. Continuous (8-h) Tc P CO₂monitoring at a lower electrode temperature (43°C) in this setting has never been formally studied. Patients under intermittent NIV were studied (n=28, aged 69±9 years, P aO₂: 71±13 mmHg, P aCO₂: 49±9 mmHg). After calibration and stabilization of Tc P CO₂(Radiometer^®Tina TCM3 capnograph), arterial blood gases (ABG) were measured and compared with transcutaneous readings. In 10 patients who underwent continuous 8-h Tc P CO₂recording, ABGs were also measured after 4 and 8 h. The correlation between Tc P CO₂and P aCO₂was highly significant (r²=0·92, P&lt;0·0001). Mean (Tc P CO₂–P aCO₂) gradient (bias) was: −2·8±3·8 mmHg; limits of agreement were: (−10·4; +4·8 mmHg). Tc P CO₂–P aCO₂gradient was lowest (i.e. within-bias±2 mmHg) between 40 and 54 mmHg, increasing below and above these values. Over 8 h, no significant drift of the Tc P CO₂signal occurred (ANOVA). No discomfort or skin lesion was noted. In conclusion, with an electrode temperature of 43°C, 8-h continuous monitoring of Tc P CO₂was well tolerated, without any local side-effects or significant drift of Tc P CO₂signal; when compared to previous reports, lowering the electrode temperature did not decrease performance for CO₂monitoring. Copyright 2001 HARCOURT PUBLISHERS LTD.

Little information exists on the impact of induced abortion on psychosexuality. Negative psychological effects and psychiatric complications due to termination of pregnancy seem to be rare. The objective of this study was to review the impact of induced abortion on sexuality and couple relationships. A systematic search of the literature was performed. Studies had to report a quantitative or qualitative evaluation of sexuality after pregnancy termination.Four studies were included. In the one prospective study using a control group, no difference in sexual functioning between groups after 1 year was reported. In the remaining observational studies, sexual dysfunction was reported in up to 30% of women after termination. Women undergoing abortion had significantly more conflicts in their partnerships. This was similar in all studies. Separation occurred in about one-quarter of all couples.Some studies report sexual dysfunction after termination of pregnancy. In about half of the couples separated after termination, abortion seemed not to have led to the separation. Psychological factors, together with relationship problems, might have played a role in failed contraception. The impact of induced abortion on sexuality needs to be studied in greater detail with rigorous methodology to draw firm conclusions.

Abstract: The efficiency of sets of acoustical features discriminating pathological voices from control voices is reported. Two strategies were compared. The first (called the ‘distance strategy’) was built upon a statistical distance of voice features to reference values obtained for a set of healthy (reference) voices. The second strategy (called the ‘range strategy’) is based on the position inside or outside normal ranges established from a reference population; results based on this strategy were presented in a previous paper. Reference values were calculated from a database of 200 healthy voices distributed into 10-year age groups ranging from 20 to 70. Comparisons were made using a second database of 220 voices, including 65 control, 51 functional dysphonia, 50 with nodules on the vocal folds and 54 recurrent nerve palsy. The phonetic material was compared of 17 French vowels: 11 vowels in a sentence, three isolated vowels and three segments (beginning, middle and end) of the sustained vowel/a/. Four acoustical features were considered for each vowel: the voice fundamental (f0) and the first three formant frequencies. Acoustical features were calculated on an ILS (Interactive Laboratory System) analysis system (workstation). The separation of each pathological group from the control group, using sets of acoustical features, was statistically assessed. From the strategy point of view, results indicated that (i) the fundamental frequency f0 was the best measure to separate normal from pathological voices with the distance strategy; (ii) when the formants were taken, the range strategy performed better in separating the voices. For classification of pathologies, the best separation coefficients were obtained with nodules and the worst with recurrent nerve palsy. Overall, it was seen that the separation between control and pathological voices was most efficient when measured using the distance strategy for f0. The range strategy was useful with formant frequencies.

This educational games tests spelling skills. It allows the player to enter up to twenty words and then it plays them back scrambled. The speller has to unscramble the letters and spell the word. The program runs on the Atari and VIC computers.

The design and construction of the silicon strip microvertex detector (SMD) of the L3 experiment at LEP are described. We present the sensors, readout electronics, data acquisition system, mechanical assembly and support, displacement monitoring systems and radiation monitoring system of the recently installed double-sided, double-layered SMD. This detector utilizes novel and sophisticated techniques for its readout.

The purpose of this study was to describe race- and ethnicity-specific characteristics of subjects lost to follow-up. For a study of community-based health interventions, adult subjects from 11 US communities were initially recruited by random digit dialing and interviewed by telephone in 1988; 2 years later, they were recontacted, and the same survey was administered a second time. Associations with loss to follow-up were assessed in separate models for whites, African Americans, Hispanic Americans, and Asian Americans. After 2 years, 40.8% of the 5,851 participants were lost to follow-up; cohort attrition was highest among African Americans (51.3%) and lowest among whites (37.5%). Age, aspects of employment, education, marital status, and income were significant independent predictors of loss to follow-up for one or more of the four racial and ethnic groups. Characteristics of subjects lost to follow-up in this telephone cohort differed among various racial and ethnic groups. After adjustment for demographic, socioeconomic, and health status variables, the important behavioral predictors of loss to follow-up were current smoking for whites (p < 0.05), having a high fat diet for African Americans (p < 0.10), consuming one or more alcoholic drinks per day for Hispanic Americans (p < 0.10), and high levels of physical activity for Asian Americans (p < 0.05).

A study of health behaviors in four communities in the western United States in 1988 provided the opportunity to compare two methods of sampling elderly respondents for a telephone interview. The Polk telemarketing lists were used to identify 1,407 respondents aged 65 years and older in four communities, where 253 respondents in the same age group were also identified by the method of random digit dialing. Individuals identified from the Polk lists received a letter prior to the initial telephone contact. The overall response rate was 49.3% for random digit dialing and 57.3% for the Polk lists. On the average, the identification of one elderly respondent using the Polk lists required about 20-25% as much interviewer time per subject identified as was required by the random digit dialing method. The elderly identified by the Polk lists were significantly older than those identified by random digit dialing, and the proportions of the Polk sample who were married, white, or had an income of greater than $10,000 were slightly higher than those of the random digit dialing sample. Among 40 variables measuring various health behaviors, indicators of health status, and participation in health-related programs and classes, only three differed significantly between the two samples. The authors conclude that sampling from commercial telemarketing lists was an efficient method of identifying elderly respondents and that in these four communities, the estimates of health behaviors and health status were comparable with those obtained by random digit dialing techniques.

Abstract: The recognition of laryngeal pathology by analysis of the voice is investigated. The fundamental frequency and the first three formants are considered. The recognition strategy is based on comparison with normal ranges calculated over 200 ordinary voices, grouped in ten age classes ranging from 20 to 70 years, for males and females. 220 test voices are studied divided into four groups: normal voices, functional dysphonia, nodules and recurrent nerve palsy. Each subject is marked according to his/her normal range. Parameters (or items) are calculated on the Interactive Laboratory System workstation. The vocalic material is composed of 11 vowels taken from a sentence. Results are given in terms of the number of values out of the normal ranges. Statistical analysis considers both parameter ability and error rates in pathology recognition. Pathology recognition shows the following error percentages: 23% for dysphonia, 14% for nodules and 33% for recurrent nerve palsy. Parameters do not show the same efficiency for voice pathology characterisation. Formants appear to be better than the fundamental frequency.

Abstract:  Soil receptiveness to a mycorrhizal association can be estimated by standard bioassay from a dose-response relationship. The method was developed using the association Pinus pinaster or Pseudotsuga menziesii with Laccaria bicolor as a model and was successfully used to characterize the receptiveness of two forest soils. From a physical and chemical point of view, both soils were receptive to the Laccaria bicolor association. Our results show that microbial factors are very important in the receptiveness of soil to ectomycorrhizal association. Ectomycorrhizal development on seedlings at outplanting sites is discussed in relation to soil receptiveness and the ecological competence of selected strains.

It has been previously shown that Japanese Americans in Seattle have significantly higher cholesterol levels than native Japanese. The present study examines the association of biological and lifestyle factors with plasma lipid and lipoprotein levels among Japanese Americans (JA) and native Japanese (NJ) to determine if these associations are consistent between these high and low cholesterol populations.

In this paper, a new approach for optimization is presented. This approach tends to imitate principles of organic evolution processes as rules for an optimization procedure. The two techniques used, haploid and diploid algorithms, are based on different organic structure modelling approaches and both use genetic concepts such as population, recombination and mutation as evolution rules to guide the optimum search. The theoretical analysis of this stochastic approach, especially with regard to issues about the global convergence, is currently in progress. However, previous tests and those presented here validated the method. These genetic algorithms are presented and their performances are compared. The comparison pertains to the convergence characterized by the number of generations needed to reach the solution, and running times are also compared with respect to applications that limit search time severely. Several complex optimization problems involving concrete applications were studied with different tuning parameters. Examples were selected to show the behaviour of the two algorithms when faced with several optima and nonlinear constraints. A practical application deals with a hydrodynamical problem, where discrete and actual variables are simultaneously handled in the same parameter optimization problem.

Results are reported from a beam test of prototype silicon microstrip detectors and front-end electronics developed for use in the LHC detector ATLAS. The detector assemblies (“modules”) were 12cm long and were read out with binary electronics. Both irradiated and unirradiated modules were measured in a 1.56T magnetic field for efficiency, noise occupancy, and position resolution as a function of bias voltage, binary hit threshold, and detector rotation angle with respect to the beam direction.

The status of the Silicon Microvertex Detector (SMD) and its installation into the LEP-L3 experiment are presented, highlighting novel features and sophisticated techniques. Preliminary results based on 1993 data are given and compared with Monte Carlo predictions, to understand the detector performances and its tracking capabilities.

A silicon microvertex detector (SMD) has been commissioned for the L3 experiment at the Large Electron-Positron colliding-beam accelerator (LEP) at CERN. The SMD is a 72,672 channel, two layer barrel tracker that is comprised of 96 ac-coupled, double-sided silicon detectors. Details of the design and construction are presented.<>

Abstract The aim of this study was to define precisely the imaging of the canals of the temporal bone by means of high-resolution computed tomography (HR CT). Based on 24 temporal bones removed from embalmed cadavers and investigated with HR CT, several canals were studied: the canal of the chorda tympani (CdT), the canal of the auricular branch of the vagus nerve (ABV), the canal of the tympanic nerve, the canal of the carotico-tympanic nerve and that of the lesser petrosal nerve. Anatomic correlations for six temporal bones were made to confirm the validity of our radiologic hypotheses. In CT, in axial sections OM 0°, the posterior canal of the CdT was visualized in 71% of cases, the ABV canal in 4%, the inferior tympanic canal in 12.5%, the carotico-tympanic canal in no cases and the canal of the lesser petrosal nerve in 50% (and in 75% with an incidence of OM+10°). In coronal incidence, the posterior canal of the CdT was seen in 20% of cases, the ABV canal in 25%, the inferior tympanic canal in 85%, the carotico-tympanic canal in 65% and that of the lesser petrosal nerve in 15%. The six anatomic comparisons confirmed the radiologic hypotheses in every case. These different structures are easy to identify in HR CT and are important to define so that any lesion (tumoral or vascular) developing in their vicinity may not be overlooked.

Abstract Summary: The aim of this study was to define the imaging of the retrotympanum precisely by means of high-resolution CT. Based on 66 scans of petrous bones performed in 49 patients observed in an otologic department, several retrotympanic structures were studied: the pyramidal eminence, ponticulus, subiculum, chordal ridge, tympanic sinus of Proctor, sinus tympani and recess of the facial n. The variations in morphology and depth were noted as well as the relationship between the pyramid and the facial canal. In a second phase the same anatomic structures were studied in 24 temporal bones removed from embalmed cadavers and investigated with the same radiologic technique. Anatomic correlations were made for six temporal bones to confirm the general applicability of our radiologic hypotheses. In CT the pyramidal eminence was visualised in 100% of cases, the chordal ridge in 52%, the ponticulus in 63% and the subiculum in 57%. As regards the different recesses, the sinus tympani was visualised in 95% of cases, the posterior tympanic sinus of Proctor in 38%, the fossula of Grivot in 47% and the facial recess in 80%. The mean depth of the sinus tympani was 2.7 mm and that of the tympanic sinus of Proctor was 1.65 mm; the fossula of Grivot was assessed as 2.1 mm and the facial recess as 2.2 mm. A better knowledge of these sinuses and their variations will aid the surgeon, particularly in a posterior tympanotomy or a retro-facial approach.

This paper describes a simple pneumatic-powered spray-control device, incorporating a piston valve and spray nozzle, which enables wounds to be treated with a biocide while pruning with a standard pneumatic secateur. The pattern of spray deposited on targets, and rate of delivery, are consistent with the requirements for protecting pruning wounds from invasion by vascular pathogens such as Eutypa lata and Chondrostereum purpureum. Field tests in two commercial apricot orchards have shown that the unit was reliable and durable in normal service and acceptable to operators accustomed to using pneumatic-powered pruning equipment.

Animals moving on and in fluids and solids move their bodies in diverse ways to generate propulsion and lift forces. In fluids, animals can wiggle, stroke, paddle or slap, whereas on hard frictional terrain, animals largely engage their appendages with the substrate to avoid slip. Granular substrates, such as desert sand, can display complex responses to animal interactions. This complexity has led to locomotor strategies that make use of fluid-like or solid-like features of this substrate, or combinations of the two. Here, we use examples from our work to demonstrate the diverse array of methods used and insights gained in the study of both surface and subsurface limbless locomotion in these habitats. Counterintuitively, these seemingly complex granular environments offer certain experimental, theoretical, robotic and computational advantages for studying terrestrial movement, with the potential for providing broad insights into morphology and locomotor control in fluids and solids, including neuromechanical control templates and morphological and behavioral evolution. In particular, granular media provide an excellent testbed for a locomotion framework called geometric mechanics, which was introduced by particle physicists and control engineers in the last century, and which allows quantitative analysis of alternative locomotor patterns and morphology to test for control templates, optimality and evolutionary alternatives. Thus, we posit that insights gained from movement in granular environments can be translated into principles that have broader applications across taxa, habitats and movement patterns, including those at microscopic scales.

Recent results by the RD2 Collaboration of a study of radiation damage of silicon detectors for the ATLAS detector at LHC are presented. The detectors have been irradiated by neutrons with fluences of up to 1.5 × 1014neutrons/cm2. The electric field in the detectors before and after type inversion, the depletion voltage and the dark current were studied.

A letter to the editor is presented in response to the periodical's stance on politics in the United States in 1944.

Adult female white mice were divided into two groups. One was fed a diet deficient in vitamin E (E-) and the other (E+) was fed the same mixture with D-a-tocopherol added (100 mg/kg chow). The following were evaluated: serum tocopherol concentrations, lung weight and sodium content, and the survival time of the animals in oxygen. Mean serum tocopherol concentrations were 2.1 ug/ml and 14.5 ug/ml (p<.005). Lung wet weight, sodium content and water content increased with time in 65% and 100% oxygen. E- mice had more sodium retention/gin lung than E+ mice (p<.05). Survival:Electron microscope studies of lungs that were fixed with glutaraldehyde at 20 cmH2O pressure showed vitamin E related differences. Oxygen (65% x 3-6 days) caused disruption of pulmonary capillary endothelial junctions and of the structure of the mitochondrial cristae in E- mice but not in E+ mice. Edema and fibrin deposition were greater in the E- group. These changes were not observed in animals kept in room air.These results indicate that vitamin E deficiency enhances the toxic effects of oxygen in mice.