Reporting risks and benefits of therapy by use of the concepts of unqualified success and unmitigated failure: applications to highly cited trials in cardiovascular medicine

BACKGROUND: The NNT (number needed to treat) and NNH (number needed to harm) are useful in conveying the results of clinical trials because they emphasize the effort that must be expended to accomplish a single, tangible outcome. But NNT conveys the effort required to achieve a positive outcome without distinguishing between the presence or absence of treatment-related adverse events. Similarly, NNH conveys harm without accounting for the achievement or lack of achievement of the benefit of therapy. Consequently, a mathematical model was developed to extend the NNT and NNH to represent the effort required to achieve "unqualified success" (NNTUS, treatment success without treatment-induced side effects) and "unmitigated failure" (NNHUF, lack of treatment success with treatment-induced side effects). METHODS AND RESULTS: NNTUS was calculated by adjusting the absolute risk reduction to allow for the probability of not incurring a treatment-related adverse event. NNHUF was similarly calculated by adjusting the absolute risk of incurring a treatment-related adverse event by the probability of not incurring any treatment-related benefit. The impact of conveying clinical trial data by the use of NNT, NNTUS, NNH, and NNHUF is illustrated by means of 11 highly cited trials identified systematically from the cardiovascular literature. The treatment effort measured by the NNTUS and the NNHUF was consistently higher than that given by the traditional NNT and NNH. These increments ranged from 1% to several hundred percent. CONCLUSIONS: The NNTUS and the NNHUF represent the treatment effort required on average to achieve 1 unqualified success and 1 unmitigated failure. NNTUS and NNHUF balance benefit and harm in an objective way and are relevant for making service delivery decisions.     

Development of a freestanding copper antiscatter grid using deep X-ray lithography

A prototype freestanding copper antiscatter grid with parallel lamellar walls has been fabricated using deep X-ray lithography and electroforming. The freestanding copper grid has square shaped lamellar walls that are 25 m thick and 1 mm tall with a 550 m period. For mammography applications, the lamellar walls have to be aligned to a point X-ray source of the X-ray system. To achieve this goal, we investigated a dynamic double-exposure technique. Our progress in using stacked exposures and use of the photoresist SU-8, both to reduce fabrication cost, is also presented.We would like to thank Francesco De Carlo, Judith Yaeger, Joseph Arko and Shenglan Xu for their assistance. Use of the APS was supported by US Department of Energy, Office of Sciences, under Contract No. W-31-109-ENG-38. We thank SRI CAT for the support of this research. The work is supported by NIH SBIR Phase II Grants: 2 R44 CA76752-02 and 5 R44 CA76752-03.This paper was presented at the Fourth International Workshop on High Aspect Ratio Microstructure Technology HARMST 2001 in June 2001.     

Virtual agent multimodal mimicry of humans

This work is about multimodal and expressive synthesis on virtual agents, based on the analysis of actions performed by human users. As input we consider the image sequence of the recorded human behavior. Computer vision and image processing techniques are incorporated in order to detect cues needed for expressivity features extraction. The multimodality of the approach lies in the fact that both facial and gestural aspects of the user’s behavior are analyzed and processed. The mimicry consists of perception, interpretation, planning and animation of the expressions shown by the human, resulting not in an exact duplicate rather than an expressive model of the user’s original behavior.     

A Virtual Head Driven by Music Expressivity

In this paper, we present a system that visualizes the expressive quality of a music performance using a virtual head. We provide a mapping through several parameter spaces: on the input side, we have elaborated a mapping between values of acoustic cues and emotion as well as expressivity parameters; on the output side, we propose a mapping between these parameters and the behaviors of the virtual head. This mapping ensures a coherency between the acoustic source and the animation of the virtual head. After presenting some background information on behavior expressivity of humans, we introduce our model of expressivity. We explain how we have elaborated the mapping between the acoustic and the behavior cues. Then, we describe the implementation of a working system that controls the behavior of a human-like head that varies depending on the emotional and acoustic characteristics of the musical execution. Finally, we present the tests we conducted to validate our mapping between the emotive content of the music performance and the expressivity parameters.     

Is there more to complicated grief than depression and posttraumatic stress disorder? A test of incremental validity.

There is growing interest in complicated grief reactions as a possible new diagnostic category for inclusion in the Diagnostic and Statistical Manual of Mental Disorders. However, no research has yet shown that complicated grief has incremental validity (i.e., predicts unique variance in functioning). The authors addressed this issue in 2 studies by comparing grief, depression, and posttraumatic stress disorder (PTSD) symptoms with different measures of functioning (interviewer ratings, friend ratings, self-report, and autonomic arousal). The 1st study (N = 73) used longitudinal data collected at 4 and 18 months postloss, and the 2nd study (N = 447) used cross-sectional data collected 2.5-3.5 years postloss. With depression and PTSD controlled, grief emerged as a unique predictor of functioning, both cross-sectionally and prospectively. The findings provide convergent support for the incremental validity of complicated grief as an independent marker of bereavement-related psychopathology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ultrasonic test of carbon composite/copper joints in the ITER divertor

The vertical targets of the ITER divertor consist of high flux units (HFU) actively cooled: CuCrZr tubes armoured by tungsten and carbon/carbon fibre composite (CFC). The armour is obtained with holed parallelepiped blocks, called monoblocks, previously prepared and welded onto the tubes by means diffusion bonding. The monoblock preparation consists in the casting of a layer of copper oxygen free (Cu OFHC) inside the monoblock hole.Each HFU is covered with more than 100 monoblocks that have to be joined simultaneously to the tube. Therefore, it is very important to individuate any defects present in the casting of Cu OFHC or at the interface with the CFC before the monoblocks are installed on the units.This paper discusses the application of non-destructive testing by ultrasound (US) method for the control of the joining interfaces between CFC monoblocks and Cu OFHC, before the brazing on the CrCrZr tube.In ENEA laboratory an ultrasonic technique (UT) suitable for the control of these joints with size and geometry according to the ITER specifications has been developed and widely tested. Real defects in this type of joints are, however, still hardly detected by UT. The CFC surface has to be machined to improve the mechanical strength of the joint. This results in a surface not perpendicular to the ultrasonic wave. Moreover, CFC is characterized by high acoustic attenuation of the ultrasonic wave and then it is not easy to get information regarding the Cu/CFC bonding. Nevertheless, the UT sharpness and simplicity pushes to perform some further study. With this purpose, a sample with artificial defects induced on the CFC/Cu interface during the Cu casting, has been manufactured and investigated, both by pulse-echo technique and by different techniques. The results obtained by the UT on this sample are reported and compared with X-ray method.     

Hydrogen isotopic enrichment: an indicator of biodegradation at a petroleum hydrocarbon contaminated field site

Compound-specific carbon and hydrogen isotope analysis was used to investigate biodegradation of benzene and ethylbenzene in contaminated groundwater at Dow Benelux BV industrial site. delta13C values for dissolved benzene and ethylbenzene in downgradient samples were enriched by up to 2+/-0.5 per thousand, in 13C, compared to the delta13C value of the source area samples. delta2H values for dissolved benzene and ethylbenzene in downgradient samples exhibited larger isotopic enrichments of up to 27+/-5 per thousand for benzene and up to 50+/-5 per thousand for ethylbenzene relative to the source area. The observed carbon and hydrogen isotopic fractionation in downgradient samples provides evidence of biodegradation of both benzene and ethylbenzene within the study area at Dow Benelux BV. The estimated extents of biodegradation of benzene derived from carbon and hydrogen isotopic compositions for each sample are in agreement, supporting the conclusion that biodegradation is the primary control on the observed differences in carbon and hydrogen isotope values. Combined carbon and hydrogen isotope analyses provides the ability to compare biodegradation in the field based on two different parameters, and hence provides a stronger basis for assessment of biodegradation of petroleum hydrocarbon contaminants.     

Improved atrial function in bicaval versus standard orthotopic techniques in cardiac transplantation

Atrial geometry is preserved in the bicaval technique of cardiac transplantation. Using Doppler echocardiography, we investigated the impact of this technique on preservation of atrial function and found that echocardiographic indexes of atrial function are improved in bicaval cardiac transplants versus the standard orthotopic transplants.     

Evaluation of pre- and postprandial growth hormone (GH)-releasing hormone-induced GH response in subjects with persistent body weight normalisation after biliopancreatic diversion

BACKGROUND: Obesity is characterised by growth hormone (GH) abnormalities, including a blunted response to stimulation and a 'paradoxical' increase after meals. The blunted GH release is reversed by a surgical intestinal bypass procedure. However, this does not mean that normal GH dynamics have been restored. The present study assessed whether post-surgical weight reduction in obese patients normalised the modulation of GH release produced by metabolic fuels. SUBJECTS: Ten obese female subjects, aged 23-54 y, were studied before and after biliopancreatic diversion (BPD). All patients, after surgery, had experienced a significant reduction in body weight (mean body mass index (BMI) 25.78 +/- 1.01 kg/m2 vs 44.68 +/- 1.73 kg/m2). Two groups were also studied as controls: Ten normal body weight female subjects and ten patients suffering from anorexia nervosa (AN, mean BMI 17.46 +/- 1.12 kg/m2). MEASUREMENTS: We have studied the GH response to a GH releasing hormone (GHRH) bolus (1 microg/kg i.v., at 13.00 h) before and after a standard meal. RESULTS: In post-BPD subjects, the GH response to GHRH in the fasting state, was clearly augmented in comparison with the pre-BPD values (peak values 18.06 +/- 4.56 vs 3.24 +/- 0.68 microg/L). In post-BPD subjects the postprandial GH response was further augmented in comparison with the fasting test (peak 30.12 +/- 4.99 microg/L, P < 0.05). This pattern was similar to that observed in anorexic patients. CONCLUSION: The surgical procedure restores a normal GH response to GHRH in the fasting state, but the 'paradoxical' GH response after meals remains present, suggesting a persistent GH derangement in such patients, which is not related to body weight per se. The surgical procedure makes obese patients similar to anorexics, in the relationships between metabolic fuels and GH secretion. The persistence of the GH postprandial response to GHRH in post-BPD subjects suggests a role for metabolic fuels in the regulation of somatostatin (SRIF) secretion.     

Temperature- and pH-dependent effect of lactate on in vitro redox stability of red meat myoglobins

Our objective was to evaluate the influence of lactate on in vitro redox stability and thermostability of beef, horse, pork, and sheep myoglobins. Lactate (200 mM) had no effect (P > 0.05) on redox stability at physiological (pH 7.4, 37 °C) and meat (pH 5.6, 4 °C) conditions. However, lactate increased (P < 0.05) metmyoglobin formation at a condition simulating stressed live skeletal muscle (pH 6.5, 37 °C). The redox stability of myoglobins at stressed live skeletal muscle and meat conditions was species–specific (P < 0.05). Myoglobin thermostability at 71 °C was lower (P < 0.05) in the presence of lactate compared with controls and was influenced (P < 0.05) by species. The results of the present study indicate that the effects of lactate on myoglobin are temperature and pH dependent. The observed lack of influence of lactate on myoglobin redox stability at meat condition suggests that the color stability of lactate-enhanced fresh meat is not due to direct interactions between the ingredient and the heme protein.