Serial assessment of pulmonary lesion volume by computed tomography allows survival prediction in invasive pulmonary aspergillosis.

BACKGROUND: Serial chest CT is the standard of care to establish treatment success in invasive pulmonary aspergillosis (IPA). Data are lacking how response should be defined. METHODS: Digital CT images from a clinical trial on treatment of IPA were re-evaluated and compared with available biomarkers. Total volume of pneumonia was added up after manual measurement of each lesion, followed by statistical analysis. RESULTS: One-hundred and ninety CT scans and 309 follow-up datasets from 40 patients were available for analysis. Thirty-one were neutropenic. Baseline galactomannan (OR 4.06, 95%CI: 1.08-15.31) and lesion volume (OR 3.14, 95%CI: 0.73-13.52) were predictive of death. Lesion volume at d7 and trend between d7 and d14 were strong predictors of death (OR 20.01, 95%CI: 1.42-282.00 and OR 15.97, 95%CI: 1.62-157.32) and treatment being rated as unsuccessful (OR 4.75, 95%CI: 0.94-24.05 and OR 40.69, 95%CI: 2.55-649.03), which was confirmed by a Cox proportional hazards model using time-dependent covariates. CONCLUSION: Any increase in CT lesion volume between day 7 and day 14 was a sensitive marker of a lethal outcome (>50%), supporting a CT rescan each one and 2 weeks after initial detection of IPA. The predictive value exceeded all other biomarkers. Further CT follow-up after response at day 14 was of low additional value. KEY POINTS: • CT evaluation offers good prediction of outcome for invasive pulmonary aspergillosis. • Predictive capability exceeds galactomannan, blood counts, and lesion count. • Any progression between day 7 and day 14 constitutes a high-risk scenario.

Modelling real-time control of WWTP influent flow under data scarcity.

In order to comply with effluent standards, wastewater operators need to avoid hydraulic overloading of the wastewater treatment plant (WWTP), as this can result in the washout of activated sludge from secondary settling tanks. Hydraulic overloading can occur in a systematic way, for instance when sewer network connections are extended without increasing the WWTP's capacity accordingly. This study demonstrates the use of rule-based real-time control (RTC) to reduce the load to the WWTP while restricting the overall overflow volume of the sewer system to a minimum. Further, it shows the added value of RTC despite the limited availability of monitoring data and information on the catchment through a parsimonious simulation approach, using relocation of spatial system boundaries and creating required input data through reverse modelling. Focus was hereby on the accurate modelling of pump hydraulics and control. Finally, two different methods of global sensitivity analysis were employed to verify the influence of parameters of both the model and the implemented control algorithm. Both methods show the importance of good knowledge of the system properties, but that monitoring errors play a minor role.

Long-wavelength chlorophylls in photosystem I of cyanobacteria: origin, localization, and functions.

The structural organization of photosystem I (PSI) complexes in cyanobacteria and the origin of the PSI antenna long-wavelength chlorophylls and their role in energy migration, charge separation, and dissipation of excess absorbed energy are discussed. The PSI complex in cyanobacterial membranes is organized preferentially as a trimer with the core antenna enriched with long-wavelength chlorophylls. The contents of long-wavelength chlorophylls and their spectral characteristics in PSI trimers and monomers are species-specific. Chlorophyll aggregates in PSI antenna are potential candidates for the role of the long-wavelength chlorophylls. The red-most chlorophylls in PSI trimers of the cyanobacteria Arthrospira platensis and Thermosynechococcus elongatus can be formed as a result of interaction of pigments peripherally localized on different monomeric complexes within the PSI trimers. Long-wavelength chlorophylls affect weakly energy equilibration within the heterogeneous PSI antenna, but they significantly delay energy trapping by P700. When the reaction center is open, energy absorbed by long-wavelength chlorophylls migrates to P700 at physiological temperatures, causing its oxidation. When the PSI reaction center is closed, the P700 cation radical or P700 triplet state (depending on the P700 redox state and the PSI acceptor side cofactors) efficiently quench the fluorescence of the long-wavelength chlorophylls of PSI and thus protect the complex against photodestruction.

[Influence of cognition on treatment outcome in geriatric patients: association between MMSE and gain in activities of daily living]. / Einfluss der Kognition auf die Behandlungsergebnisse in der Geriatrie : Zusammenhang von MMSE und Zugewinn in den Alltagsaktivitäten.

BACKGROUND: Cognitive impairment or dementia influence the results of geriatric treatment. The aim of the study was to quantify this influence. PATIENTS AND METHODS: Data of 2527 patients from the years 2006 to 2009 were analysed in order to quantify the influence of cognition measured with the Mini Mental Status Examination (MMSE) on the improvement of activities of daily living as reflected by the Functional Independence Measure (FIM). RESULTS: Impaired cognition is accompanied by a lower FIM score on admission and on discharge. But the improvement of the FIM of slightly cognitively impaired patients (MMSE 20-26) is the same as in patients without cognitive impairment (MMSE 27-30). Patients with a MMSE below 20 points have smaller improvements in their FIM score but nevertheless 40 % of the patients with a MMSE of 10-19 and still 30 % of the patients with a MMSE of 0-9 points show better improvements than the average of all patients. CONCLUSION: Patients with a MMSE below 20 should not generally be excluded from geriatric treatment, but individual factors should be considered.

Protein dynamics-induced variation of excitation energy transfer pathways.

Strong anticorrelation between the fluorescence emission of different emitters is observed by employing single-molecule fluorescence spectroscopy on photosystem I at cryogenic temperatures. This anticorrelation demonstrates a time-dependent interaction between pigments participating in the exciton transfer chain, implying that uniquely defined energy transfer pathways within the complex do not exist. Fluctuations of the chromophores themselves or their immediate protein surroundings induce changes in their site energy, and, as a consequence, these fluctuations change the coupling within the excitation transfer pathways. The time scales of the site energy fluctuations of the individual emitters do not meet the time scales of the observed correlated emission behavior. Therefore, the emitters must be fed individually by energetically higher lying states, causing the observed intensity variations. This phenomenon is shown for photosystem I pigment-protein complexes from 2 different cyanobacteria (Thermosynechococcus elongatus and Synechocystis sp. PCC 6803) with strongly different spectral properties underlining the general character of the findings. The variability of energy transfer pathways might play a key role in the extreme robustness of light-harvesting systems in general.

A kernel-based method to determine optimal sampling times for the simultaneous estimation of the parameters of rival mathematical models.

When several models are proposed for one and the same process, experimental design techniques are available to design optimal discriminatory experiments. However, because the experimental design techniques are model-based, it is important that the required model predictions are not too uncertain. This uncertainty is determined by the quality of the already available data, since low-quality data will result in poorly estimated parameters, which on their turn result in uncertain model predictions. Therefore, model discrimination may become more efficient and effective if this uncertainty is reduced first. This can be achieved by performing dedicated experiments, designed to increase the accuracy of the parameter estimates. However, performing such an additional experiment for each rival model may undermine the overall goal of optimal experimental design, which is to minimize the experimental effort. In this article, a kernel-based method is presented to determine optimal sampling times to simultaneously estimate the parameters of rival models in a single experiment. The method is applied in a case study where nine rival models are defined to describe the kinetics of an enzymatic reaction (glucokinase). The results clearly show that the presented method performs well, and that a compromise experiment is found which is sufficiently informative to improve the overall accuracy of the parameters of all rival models, thus allowing subsequent design of an optimal discriminatory experiment.

Handwriting difficulties in primary school children: a search for underlying mechanisms.

OBJECTIVE: This study investigated the contribution of perceptual-motor dysfunction and cognitive planning problems to the quality or speed of handwriting in children with handwriting problems (HWP). METHOD: Twenty-nine children with HWP and 20 classroom peers attending regular schools (grade 2 and grade 3) were tested with regard to visual perception, visual-motor integration, fine motor coordination, and cognitive planning abilities. RESULTS: The HWP group scored significantly lower on visual perception, visual-motor integration, fine motor coordination, and cognitive planning in comparison with classroom controls. Regression analyses showed that visual-motor integration was the only significant predictor for quality of handwriting in the HWP group, whereas fine motor coordination (i.e., unimanual dexterity) was the only significant predictor of quality of handwriting in the control group. CONCLUSIONS: Results suggest that two different mechanisms underlie the quality of handwriting in children with and without handwriting problems. Poor quality of handwriting of children with HWP seems particularly related to a deficiency in visual-motor integration.

Neural correlates of ticklishness in the rat somatosensory cortex.

Rats emit ultrasonic vocalizations in response to tickling by humans. Tickling is rewarding through dopaminergic mechanisms, but the function and neural correlates of ticklishness are unknown. We confirmed that tickling of rats evoked vocalizations, approach, and unsolicited jumps (Freudensprünge). Recordings in the trunk region of the rat somatosensory cortex showed intense tickling-evoked activity in most neurons, whereas a minority of cells were suppressed by tickling. Tickling responses predicted nontactile neural responses to play behaviors, which suggests a neuronal link between tickling and play. Anxiogenic conditions suppressed tickling-evoked vocalizations and trunk cortex activity. Deep-layer trunk cortex neurons discharged during vocalizations, and deep-layer microstimulation evoked vocalizations. Our findings provide evidence for deep-layer trunk cortex activity as a neural correlate of ticklishness.

Cloning and sequencing of glutamate mutase component E from Clostridium tetanomorphum.

The nucleotide sequence of the large subunit E of glutamate mutase of Clostridium tetanomorphum was determined. The protein consists of 483 amino acids and is not made in a precursor form, thus excluding the possibility of subunit E being a pyruvoyl enzyme. It shows no homology to any other protein in the database, and while binding coenzyme B12, a conspicuous B12 binding motif, shared amongst other proteins, is not detectable at the sequence level.

Changes in polysome profiles accompany trypanosome development.

Development of the protozoan pathogen Trypanosoma brucei involves regulated changes in parasite structure, biochemistry, and the cell cycle. The transition of slender blood forms into stumpy bloodforms includes cell cycle arrest and a decrease in protein synthesis. The next stage in the development cycle, the procyclic form, shows increased protein synthesis and proliferates. To address the mechanism of the cyclical changes in protein synthesis, we examined two parameters: polyadenylation of mRNA and ribosome loading. We developed a method for analytical polyribosome analysis in T. brucei which provided excellent results with regard to reproducibility, yield of mRNA densely loaded with ribosomes, and separation of mRNA associated with different numbers of polyribosomes. Use of this technique allowed us to determine that the polysome profiles of the different developmental stages are distinctly different, with higher ribosome loading in the proliferating stages. The lengths of the poly(A) tails on the total population of RNA from the different developmental stages showed no significant variation. These data indicate that changes in polysome loading of mRNAs accompany development, and that they do not reflect bulk changes in polyadenylation. We speculate that developmental changes in translation reflect reduced translational initiation.

Skin test anergy in advanced heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy.

Skin tests to recall antigens are performed as indicators of clinical outcomes in heart failure (HF). A diminution in the response to recall antigens, termed "anergy," is regarded as an indication of poorer clinical prognosis, although little analysis has been done to support that conclusion. Patients with advanced HF (n=222) in New York Heart Association classes III and IV, with complete datasets for all of the variables, were studied. The sample was 77% men, mean age 52+/-12 years, and left ventricular ejection fraction, 21+/-7. Patients with ischemic (n=113) and idiopathic (n=109) disease were analyzed separately. The relation of anergy to 1-year mortality and selected hemodynamic factors, blood chemistries, medications, and nutritional status markers was analyzed. Anergy was present in 45% (47% idiopathic and 42% ischemic) of patients. Anergy was related to 1-year mortality (univariate p=0.038) in patients with ischemic, but not idiopathic, HF. Anergic patients with ischemic HF had shorter survival times (p=0.035). Lower cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides were predictors (p <0.001) of mortality in idiopathic HF. In ischemic HF, lower cholesterol, LDL, and triglycerides were univariate predictors (p <0.001, p=0.004, and p=0.005, respectively) of skin test anergy, but not mortality. Thus, there were distinct differences in clinical correlates of skin test anergy in patients with idiopathic and ischemic HF. This study supports evaluation of anergy to skin tests as one of the markers of mortality in patients with ischemic HF.

Quality of life in patients with advanced heart failure.

Although evaluation of the treatment of congestive heart failure is usually based on objective clinical outcomes, patient self-assessment is increasingly recognized as an important component of evaluation. A study was designed to measure the quality of life of 134 patients with symptoms of advanced heart failure who were being evaluated for possible heart transplantation. The patients' quality of life was assessed using a mix of subjective and objective measures, including functional status, physical symptoms, emotional state, and psychosocial adaptation. There was no significant relationship between patients' cardiac ejection fraction and any quality-of-life measures; however, the results of a 6-minute walking test, New York Heart Association classification, and self-reported functional status were all significantly correlated with psychosocial adjustment. Self-reported functional status, depression, and hostility accounted for 43% of the variance in total psychosocial adjustment to illness. These findings support the inclusion of quality of life as an outcome measure in any evaluation of treatment efficacy and suggest that interventions to improve the quality of life of patients with advanced heart failure need to be targeted at reducing depression and hostility and increasing daily activity levels.

Predictors of quality of life in women with heart failure. SOLVD Investigators. Studies of Left Ventricular Dysfunction.

BACKGROUND: Two and one half million women have heart failure (HF). Yet little is known about quality of life (QOL) in this population and the factors influencing it. Given the importance of QOL as an outcome of care, we conducted a study to evaluate predictors of QOL in women with HF. METHODS: Using baseline QOL data collected in the Studies of Left Ventricular Dysfunction (SOLVD) trials, we studied predictors of QOL in 691 women with HF. Univariate, bivariate, and multiple regression analyses were used. Potential predictors included age, education, tobacco use, social isolation, life stresses, comorbidity index, New York Heart Association (NYHA) class, HF symptoms, etiology, and medications. We measured global QOL and QOL dimensions of physical function, emotional distress, and social and general health. RESULTS: Women were older (61+/-10.5 years), predominantly Caucasian (75%), and their mean ejection fraction was 0.27 (+/-6.51). Variables with the strongest relationship to QOL included dyspnea, NYHA class, and life stresses. As dyspnea, life stresses, and NYHA class increased, QOL decreased. Additionally, smoking behavior and vasodilator use was associated with decreased QOL. Heart failure etiology of ischemic origin was associated with decreased social life satisfaction, and use of digitalis was predictive of increased social life satisfaction. Finally, increasing age was related to an increase in general life satisfaction. CONCLUSION: Symptom amelioration, which may improve functional ability, has the greatest potential for increasing QOL in women with HF. Programs to increase physical activity in women with HF should be developed and tested. Finally, clinicians may need to optimize HF medications in women.

Synchronization of visual responses in the superior colliculus of awake cats.

Multi-unit responses to moving stimuli were recorded simultaneously from several sites in the superior colliculus of awake cats. Correlation analysis revealed that response synchronization was a prominent feature of visually evoked neural activity in both superficial and deep collicular layers. Responses at about half of the recordings separated by < or = 1 mm showed significant correlations. The synchronized responses oscillated in the gamma frequency range (30-70 Hz) which contrasts to conditions in anaesthetized cats where oscillations predominantly occurred in the alpha and beta frequency range (10-20 Hz). Response synchronization was most pronounced with coherent motion stimuli and broke down with incoherent stimuli. These results agree with previous findings on corticotectal synchronization and support the hypothesis that synchronization in the millisecond range serves to group collicular neurons into functionally coherent assemblies.

Functional architecture of the mystacial vibrissae.

We investigated the transduction operation and function of the mystacial vibrissae, using a comparative morphological analysis and behavioral experiments in rats. Vibrissal architecture was documented in a series of mammals to identify evolutionary conserved features of vibrissal organization. As a result of this analysis, we distinguish between a frontal microvibrissal system and macrovibrissal system of the mystacial pad. The latter was invariably comprised of whiskers aligned in regular rows. In each row, whiskers were oriented perpendicular to the animal's rostrocaudal axis; all shared a specific dorsoventral orientation. In all species, progressing from rostral to caudal in any vibrissal row, there was a precisely exponential increase in whisker length. Each whisker appeared to act as a lever-like transducer, providing information as to whether or not--but not where--an individual vibrissa had been deflected. The rat's frontal microvibrissae system was found to have a vibrissa tip density that was about 40 times higher than that of the mystacial macrovibrissae. In behavioral studies spatial tasks and object recognition tasks were used to investigate (a) search behaviors; (b) single whisker movements; (c) object recognition ability; and (d) effects of selective macro- or microvibrissae removal on task performances. A clear distinction between the functional roles of macro- and microvibrissae was demonstrated in these studies. Mystacial macrovibrissae were critically involved in spatial tasks, but were not essential for object recognition. Microvibrissae were critically involved in object recognition tasks, but were not essential for spatial tasks. A synthesis of these morphological and behavioral data led to the following functional concept: The mystacial macrovibrissae row is a distance decoder. Its function is to derive head centered obstacle/opening contours at the various dorsoventral angles represented by vibrissal rows. This distance detector model is functionally very different from traditional concepts of whisker function, in which the mystacial whiskers were hypothesized to form a fine grain skin-like object-recognizing tactile surface.

Psychosocial predictors of AIDS risk behavior and drug use behavior in homeless and drug addicted women of color.

The present study examined a causal model consisting of personal and social resources, threat appraisal processes, coping styles, and barriers to risk reduction as predictors of general AIDS risk and specific drug use behaviors among homeless African American (N = 714) and Latina (N = 691) women. The model, which was based on a stress and coping framework, supported many of the hypothesized relationships. Active coping was associated with fewer general AIDS risk behaviors for both groups and less specific drug use behavior among African American women. Specific drug use behavior was predicted by high threat appraisal and avoidant coping for both groups. Ethnic differences and implications for intervention are discussed.

AIDS risk behaviors, knowledge, and attitudes among pregnant adolescents and young mothers.

This study assessed AIDS risk behaviors, knowledge, and related attitudes of pregnant adolescents and young mothers (n = 151). Results revealed that a substantial portion of the sample engaged in sexual behaviors (e.g., unprotected sex and multiple sex partners) that increased their risk for acquiring HIV and possibly transmitting the disease to their children. Knowledge about major modes of HIV transmission was high; however, commonly held misconceptions were expressed concerning the spread of disease and methods of prevention. Results suggest that neither the experience of having an unplanned pregnancy nor knowing about HIV transmission was a sufficient motivator to reduce risk behaviors in this sample.

Evaluation of high-risk smoking practices used by the homeless.

The purpose of this study was to evaluate the prevalence of high-risk smoking practices in a homeless population. High-risk cigarette smoking practices include misuse of tobacco products or alternative methods of cigarette smoking that increase the likelihood of ingestion of toxic substances and infectious agents that can potentiate the hazards associated with cigarette smoking. An 84-item questionnaire was developed by the researcher to measure these practices. Fifty-six male and three female homeless people were interviewed in downtown Los Angeles. The most common high-risk smoking practices were cigarette sharing (86%); smoking cigarettes remade from discarded cigarette butts and filters (71%); smoking cigarettes remade by others (63%); smoking discarded cigarette butts (63%); blocking filter vents (24%); using things other than tobacco, such as discarded cigarette filters and drugs, in remaking cigarettes (22%); and smoking discarded cigarette filters (19%). These high-risk smoking practices pose a greater risk of exposure to toxins trapped in filters and tobacco remains and increase the threat of infectious disease transmission. The long-term effects of high-risk smoking practices among the homeless have potential economic implications for society.

Comorbidity, nutritional intake, social support, weight, and functional status over time in older cancer patients receiving radiotherapy.

It is essential that nurses gain insight about the responses of older adults to standard anticancer therapies because there is ongoing concern about whether the elderly are affected adversely by the prescribed therapy. The purpose of this longitudinal prospective study was to describe selected outcomes and their relationships in a sample of 45 elderly (mean age 69.8 years; range 61-86) patients receiving radiotherapy for either breast (42%) or lung (58%) cancer. The outcome variables were weight and multidimensional functional status; moderator variables were co-morbidity, nutritional intake, estimated adequacy of intake, radiation dose, side effects, and social support. Data were collected at the beginning of radiation (T1), the middle of therapy (T2), the conclusion of therapy (T3), and three months post radiation (T4). Although 81.4% had some concurrent condition, those with a comorbid condition did not respond significantly differently from those without a comorbid condition on any of the major variables at any of the four times. At none of the four times was the caloric intake adequate to meet the estimated energy requirements for usual activity (range 67.9-71.5%). However, caloric intake was not significantly related to weight at any of the four times. There was a significant weight decrease from beginning of therapy to the middle of therapy and from the beginning of therapy to conclusion of therapy. The percentage of calories contributed by protein was significantly correlated with weight during radiotherapy, and protein calories consumed at the previous time were correlated with weight at T2 and T3. In contrast, the percentage of calories contributed by carbohydrate intake was significantly negatively correlated with two of the four functional status measures at each time, but was not related to weight. In addition carbohydrate calories consumed at the previous time also were related to one or more functional status measures at succeeding time points. Almost no relationships were found between social support and the outcome measures of weight and functional status. Scores on three of the four functional status measures suggest improvement over time from initiation of radiation to 3 months after therapy. Scores on the fourth measure, Overall Health Rating, suggest a slight decline; however, the average score reflects good overall health. These findings provide evidence that this group of elderly, the great majority of whom had at least one comorbid condition, tolerated the course of radiation with less than adequate intake for usual activity, a slight decrease in mean weight, but without major disruptions in functional status.(ABSTRACT TRUNCATED AT 400 WORDS)