Hyperhaploidy is a novel high-risk cytogenetic subgroup in multiple myeloma.

Hyperhaploid clones (24-34 chromosomes) were identified in 33 patients with multiple myeloma (MM), demonstrating a novel numerical cytogenetic subgroup. Strikingly, all hyperhaploid karyotypes were found to harbor monosomy 17p, the single most important risk stratification lesion in MM. A catastrophic loss of nearly a haploid set of chromosomes results in disomies of chromosomes 3, 5, 7, 9, 11, 15, 18, 19 and 21, the same basic set of odd-numbered chromosomes found in trisomy in hyperdiploid myeloma. All other autosomes are found in monosomy, resulting in additional clinically relevant monosomies of 1p, 6q, 13q and 16q. Hypotriploid subclones (58-68 chromosomes) were also identified in 11 of the 33 patients and represent a duplication of the hyperhaploid clone. Analysis of clones utilizing interphase fluorescence in situ hybridization (iFISH), metaphase FISH and spectral karyotyping identified either monosomy 17 or del17p in all patients. Amplification of 1q21 was identified in eight patients, demonstrating an additional high-risk marker. Importantly, our findings indicate that current iFISH strategies may be uninformative or ambiguous in the detection of these clones, suggesting this patient subgroup maybe underreported. Overall survival for patients with hyperhaploid clones was poor, with a 5-year survival rate of 23.1%. These findings identify a distinct numerical subgroup with cytogenetically defined high-risk disease.

Brief communication: MaqFACS: A muscle-based facial movement coding system for the rhesus macaque.

Over 125 years ago, Charles Darwin (1872) suggested that the only way to fully understand the form and function of human facial expression was to make comparisons with other species. Nevertheless, it has been only recently that facial expressions in humans and related primate species have been compared using systematic, anatomically based techniques. Through this approach, large-scale evolutionary and phylogenetic analyses of facial expressions, including their homology, can now be addressed. Here, the development of a muscular-based system for measuring facial movement in rhesus macaques (Macaca mulatta) is described based on the well-known FACS (Facial Action Coding System) and ChimpFACS. These systems describe facial movement according to the action of the underlying facial musculature, which is highly conserved across primates. The coding systems are standardized; thus, their use is comparable across laboratories and study populations. In the development of MaqFACS, several species differences in the facial movement repertoire of rhesus macaques were observed in comparison with chimpanzees and humans, particularly with regard to brow movements, puckering of the lips, and ear movements. These differences do not seem to be the result of constraints imposed by morphological differences in the facial structure of these three species. It is more likely that they reflect unique specializations in the communicative repertoire of each species.

Mapping the contribution of single muscles to facial movements in the rhesus macaque.

The rhesus macaque (Macaca mulatta) is the most utilized primate model in the biomedical and psychological sciences. Expressive behavior is of interest to scientists studying these animals, both as a direct variable (modeling neuropsychiatric disease, where expressivity is a primary deficit), as an indirect measure of health and welfare, and also in order to understand the evolution of communication. Here, intramuscular electrical stimulation of facial muscles was conducted in the rhesus macaque in order to document the relative contribution of each muscle to the range of facial movements and to compare the expressive function of homologous muscles in humans, chimpanzees and macaques. Despite published accounts that monkeys possess less differentiated and less complex facial musculature, the majority of muscles previously identified in humans and chimpanzees were stimulated successfully in the rhesus macaque and caused similar appearance changes. These observations suggest that the facial muscular apparatus of the monkey has extensive homology to the human face. The muscles of the human face, therefore, do not represent a significant evolutionary departure from those of a monkey species. Thus, facial expressions can be compared between humans and rhesus macaques at the level of the facial musculature, facilitating the systematic investigation of comparative facial communication.

Long-term trends in water quality and their impact on macroinvertebrate assemblages in eutrophic lowland rivers.

Long-term trends in water quality in eutrophic lowland rivers in eastern England were investigated and their impact on macroinvertebrate assemblages studied. Dissolved oxygen (DO) declined significantly in eight rivers in Essex and Suffolk over 40 years to 1998. Chloride concentrations significantly increased during the same period in most rivers. Total oxidized nitrogen and soluble reactive phosphorus increased until the 1980s, then began to decline. Biotic scores (Lincoln Quality Index) generally increased over 14 years to 1998 and there were significant positive relationships between biotic scores and several nutrients. Invertebrate families and environmental variables sampled over the eight rivers in a dry year (1997) and a wet year (1998) were subjected to multivariate analysis. River stretches were grouped according to substrate requirements of indicator invertebrates. In the dry year, those river stretches behind mills or immediately downstream of sewage treatment works (STW) were grouped. In the wet year, there was only one separate group, comprising sites downstream of STWs. Nutrients, DO and low flows have a much greater influence on water quality, and hence invertebrate assemblages, during drought years than during wet years.

Reduction in photosynthetic efficiency of Cladophora glomerata, induced by overlying canopies of Lemna spp.

The duckweeds Lemna minor L. and L. minuscula Herter reduced PSII quantum efficiency (F'q/F'm) of the filamentous green alga Cladophora glomerata Kützing by up to 42% over seven days when floating above mats of C. glomerata in containers. Dissolved oxygen (DO) increased by 23% at 30 degrees C in containers with C. glomerata over controls. But when the water surface in the containers was covered with Lemna spp. floating above C. glomerata, DO was 83% lower at 30 degrees C over seven days than in control samples with no duckweed or alga. Dissolved oxygen was lower beneath a thick mat (1 cm) of either Lemna spp. covering the surface than under a thin layer (single-frond canopy). PAM fluorimetry showed that maximum PSII efficiency (Fv/Fm) of C. glomerata in containers was reduced under a canopy of L. minor by 17% over seven days, and under L. minuscula by 22%. F'q/F'm of C. glomerata in containers exposed to 51 micromol m(-2) s(-1) PPFD decreased under a canopy of L. minor by 16% over seven days, and under L. minuscula by 19% compared to controls. When light response curves were compared, F'q/F'm was significantly reduced under canopies of L. minor at the highest temperatures tested (28 degrees C and 30 degrees C). L. minor significantly reduced relative electron transport rate (rel. ETR) of the controls by up to 71% at 30 degrees C. Relative electron transport rate did not reach light saturation point (Esat) except at 28 degrees and 30 degrees C under mats of L. minor. Whereas the highest rate of production (rel. ETRmax) and Esat increased with temperature in controls, under a canopy of Lemna, decreases were observed. It is suggested that, during periods of high summer temperature and irradiance, shading inhibits oxygenic photosynthesis in mats of C. glomerata beneath canopies of Lenma spp. This results in less oxygen being produced by the C. glomerata (oxygen produced by Lemna spp. is not released into the water), and this may further inhibit the C. glomerata by limiting oxygen-dependent electron transport and/or photorespiration. This feedback loop could lead to the eventual senescence of the C. glomerata. The combination of low oxygen, high temperature and stressed filamentous algae, particularly in slow or standing water, may help to explain sudden collapses in DO concentration, with detrimental effects on water quality downstream.

Rearing experience differentially affects somatic and cardiac startle responses in rhesus monkeys (Macaca mulatta).

The present study reports, for the first time, somatic and cardiac responses to acoustic startle in 2 groups of rhesus monkeys (Macaca mulatta) with different rearing experiences. Both groups showed a significant direct relationship between startle amplitude and the intensity of the acoustic startle stimulus (80-120 dB) and rapid heart rate acceleration after a 120-dB stimulus. Monkeys reared with a same-age peer (PR) showed higher startle amplitudes than those reared with their mothers (MR), consistent with rearing effects in rodents. The MR monkeys, however, showed faster heart rate acceleration of greater overall magnitude than that of the PR group. The results are discussed with regard to a monkey model for neuropsychiatric disease.

Trials and tribulations in deploying digital imaging network and picture archiving and communication system--film to filmless in 80 days.

The Naval Medical Center Portsmouth (NMCP) was constructed with the intention of deploying a picture archiving and communications system (PACS). All necessary infrastructures were installed and considerable planning was done during construction with the belief that this would make the deployment of the PACS much simpler. This was true during the early deployment; however, as time passed and the system was more heavily used, significant problems arose. User/operator-related and hardware/software-related problems were encountered. Although, most have been corrected, some have persisted and will require considerable manpower and/or fiscal resources to correct. The lesson learned is that no matter how much preparation is done for deploying PACS, many significant problems will surface as the system is used that will require the continued attention of the deployment project officer.

Quality-control issues on high-resolution diagnostic monitors.

Previous literature indicates a need for more data collection in the area of quality control of high-resolution diagnostic monitors. Throughout acceptance testing, which began in June 2000, stability of monitor calibration was analyzed. Although image quality on all monitors was found to be acceptable upon initial acceptance testing using VeriLUM software by Image Smiths, Inc (Germantown, MD), it was determined to be unacceptable during the clinical phase of acceptance testing. High-resolution monitors were evaluated for quality assurance on a weekly basis from installation through acceptance testing and beyond. During clinical utilization determination (CUD), monitor calibration was identified as a problem and the manufacturer returned and recalibrated all workstations. From that time through final acceptance testing, high-resolution monitor calibration and monitor failure rate remained a problem. The monitor vendor then returned to the site to address these areas. Monitor defocus was still noticeable and calibration checks were increased to three times per week. White and black level drift on medium-resolution monitors had been attributed to raster size settings. Measurements of white and black level at several different size settings were taken to determine the effect of size on white and black level settings. Black level remained steady with size change. White level appeared to increase by 2.0 cd/m2 for every 0.1 inches decrease in horizontal raster size. This was determined not to be the cause of the observed brightness drift. Frequency of calibration/testing is an issue in a clinical environment. The increased frequency required at our site cannot be sustained. The medical physics division cannot provide dedicated personnel to conduct the quality-assurance testing on all monitors at this interval due to other physics commitments throughout the hospital. Monitor access is also an issue due to radiologists' need to read images. Some workstations are in use 7 AM to 11 PM daily. An appropriate monitor calibration frequency must be established during acceptance testing to ensure unacceptable drift is not masked by excessive calibration frequency. Standards for acceptable black level and white level drift also need to be determined. The monitor vendor and hospital staff agree that currently, very small printed text is an acceptable method of determining monitor blur, however, a better method of determining monitor blur is being pursued. Although monitors may show acceptable quality during initial acceptance testing, they need to show sustained quality during the clinical acceptance-testing phase. Defocus, black level, and white level are image quality concerns, which need to be evaluated during the clinical phase of acceptance testing. Image quality deficiencies can have a negative impact on patient care and raise serious medical-legal concerns. The attention to quality control required of the hospital staff needs to be realistic and not have a significant impact on radiology workflow.

Cognitive and physiological markers of emotional awareness in chimpanzees (Pan troglodytes).

The ability to understand emotion in others is one of the most important factors involved in regulating social interactions in primates. Such emotional awareness functions to coordinate activity among group members, enable the formation of long-lasting individual relationships, and facilitate the pursuit of shared interests. Despite these important evolutionary implications, comparative studies of emotional processing in humans and great apes are practically nonexistent, constituting a major gap in our understanding of the extent to which emotional awareness has played an important role in shaping human behavior and societies. This paper presents the results of two experiments that examine chimpanzees' responses to emotional stimuli. First, changes in peripheral skin temperature were measured while subjects viewed three categories of emotionally negative video scenes; conspecifics being injected with needles (INJ), darts and needles alone (DART), and conspecific directing agonism towards the veterinarians (CHASE). Second, chimpanzees were required to use facial expressions to categorize emotional video scenes, i.e., favorite food and objects and veterinarian procedures, according to their positive and negative valence. With no prior training, subjects spontaneously matched the emotional videos to conspecific facial expressions according to their shared emotional meaning, indicating that chimpanzee facial expressions are processed emotionally, as are human expressions. Decreases in peripheral skin temperature, indicative of negative sympathetic arousal, were significantly lower when subjects viewed the INJ and DART videos, compared to the CHASE videos, indicating greater negative arousal when viewing conspecifics being injected with needles, and needles themselves, than when viewing conspecifics engaged in general agonism.

Recognizing facial cues: individual discrimination by chimpanzees (Pan troglodytes) and rhesus monkeys (Macaca mulatta).

Faces are one of the most salient classes of stimuli involved in social communication. Three experiments compared face-recognition abilities in chimpanzees (Pan troglodytes) and rhesus monkeys (Macaca mulatta). In the face-matching task, the chimpanzees matched identical photographs of conspecifics' faces on Trial 1, and the rhesus monkeys did the same after 4 generalization trials. In the individual-recognition task, the chimpanzees matched 2 different photographs of the same individual after 2 trials, and the rhesus monkeys generalized in fewer than 6 trials. The feature-masking task showed that the eyes were the most important cue for individual recognition. Thus, chimpanzees and rhesus monkeys are able to use facial cues to discriminate unfamiliar conspecifics. Although the rhesus monkeys required many trials to learn the tasks, this is not evidence that faces are not as important social stimuli for them as for the chimpanzees.

Brain temperature asymmetries and emotional perception in chimpanzees, Pan troglodytes.

The lateralization of emotion has received a great deal of attention over the last few decades, resulting in two main theories. The Right Hemisphere Theory states that the right hemisphere is primarily responsible for emotional processes, while the Valence Theory suggests that the right hemisphere regulates negative emotion and the left hemisphere regulates positive emotion. Despite the important implications of these theories for the evolution of emotion processes, few studies have attempted to assess the lateralization of emotion in non-human primates. This study uses the novel technique of measuring tympanic membrane temperature (Tty) to assess asymmetries in the perception of emotional stimuli in chimpanzees. The tympanic membrane is an indirect, but reliable, site from which to measure brain temperature, and is strongly influenced by autonomic and behavioral activity. Six chimpanzees were shown positive, neutral, and negative emotional videos depicting scenes of play, scenery, and severe aggression, respectively. During the negative emotion condition, right Tty was significantly higher than the baseline temperature. This effect was relatively stable, long lasting, and consistent across subjects. Temperatures did not change significantly from baseline in the neutral or positive emotion condition, although a significant number of measurements showed increased left Tty during the neutral emotion condition. These data suggest that viewing emotional stimuli results in asymmetrical changes in brain temperature, in particular increased right Tty during the negative emotion condition, evidence of emotional arousal in chimpanzees, and in providing partial support of both the Right Hemisphere and Valence Theories of emotional lateralization in our closest living ancestor.

Enhanced surveillance of meningococcal disease in the West Midlands: 1996 to 1998.

Surveillance of meningococcal disease is vital if we are to respond to a changing burden of disease, but current sources of routine data suggest different trends. A scheme for enhanced surveillance of meningococcal disease began in the West Midlands in January 1996 using several data sources, including case reporting from consultants in communicable disease control, data from the PHLS Meningococcal Reference Unit, and monitoring of statutory notifications and laboratory reports. One thousand two hundred and twenty-eight cases of probable meningococcal infection were identified in three years (1996-1998), 594 of which were laboratory confirmed. Routine data for the same period yielded smaller totals--920 notifications and 412 laboratory reports--suggesting that these sources underestimate incidence by 25% to 30%. Diagnosis by polymerase chain reaction became increasingly important, and accounted for 38% of confirmed cases in 1998. A significant excess of male cases was observed (p < 0.01), most obvious in children under 5 years of age. There was no increase in N. meningitidis C2a strains, which had been identified as a threat nationally. A national system of enhanced surveillance has now been set up to inform programmes that aim to reduce the burden of meningococcal infection.

Why faces may be special: evidence of the inversion effect in chimpanzees.

Five chimpanzees were tested on their ability to discriminate faces and automobiles presented in both their upright and inverted orientations. The face stimuli consisted of 30 black and white photographs, 10 each of unfamiliar chimpanzees (Pan troblodytes), brown capuchins (Cebus apella), and humans (Homo sapiens). Ten black and white photographs of automobiles were also used. The stimuli were presented in a sequential matching-to-sample (SMTS) format using a computerized joystick-testing apparatus. Subjects performed better on upright than inverted stimuli in all classes. Performance was significantly better on upright than inverted presentations of chimpanzee and human faces but not on capuchin monkey faces or automobiles. These data support previous studies in humans that suggest the inversion effect occurs for stimuli for which subjects have developed an expertise. Alternative explanations for the inversion effect based on the type of spatial frequency contained in the stimuli are also discussed. These data are the first to provide evidence for the inversion effect using several classes of face stimuli in a great ape species.

Autopsy of a cadaver containing strontium-89-chloride.

An autopsy was performed on a patient who died after receiving 89Sr-chloride for treatment of bone pain from metastatic prostate carcinoma. Coordination between nuclear medicine physicians, radiation safety division personnel and pathologists resulted in minimal radiation exposure and the acquisition of dosimetry data.

Haptic discrimination in capuchin monkeys (Cebus apella): evidence of manual specialization.

Two experiments investigated the effects of haptic and visual discrimination on hand preference in 22 brown capuchin monkeys (Cebus apella). The percentage of left-handed subjects in Experiment 1 were 63.6%, 45.5%, and 18.2% for haptic, bipedal, and quadrupedal reaching, respectively. In Experiment 2, the haptic demands of the task were manipulated by using additional food types and another tactile medium. Left-hand preferences were further strengthened when reaching into water compared to pineshavings in Experiment 1. Reaching with no tactile interference resulted in equal numbers of lateralized and nonlateralized subjects. These results show that when reaching demands the use of haptic cues, as opposed to visual ones, monkeys shift towards greater left hand use. This is consistent with what is known about right hemisphere superiority for haptic discrimination in humans.

Phospholipase C mediated inhibition of factor VII requires triglyceride-rich lipoproteins.

The reduction of plasma factor VII (FVII) activity by phospholipase C (PLC), in vitro, has been proposed as a possible indication of a risk of cardiovascular disease. The ability of PLC to reduce FVII activity was found to require calcium ions and the presence of triglyceride-rich lipoproteins (e.g. chylomicra and very-low density lipoproteins) rather than high or low density lipoproteins. The PLC-mediated reduction of FVII activity was prevented by pre-incubation of PLC with chylomicra, before adding FVII, and this suggests that PLC may act on triglyceride-rich lipoproteins already bound to FVII in order to reduce FVII activity. At optimal PLC concentration, the extent of the reduction in FVII activity was proportional to the concentration of chylomicra. The detergent, Tween, prevented any loss of FVII activity, in both plasma and purified systems, if it was present at the beginning of the incubation with PLC. Addition of Tween, but not EDTA, after inhibition of FVII activity had occurred, caused a partial restoration of FVII activity. It is concluded that PLC reduces FVII activity by modifying triglyceride-rich lipoproteins to a form which binds to FVII, independently of calcium ions, and which inhibits procoagulant activity. The detection of PLC-sensitive procoagulant activity. The detection of PLC-sensitive FVII activity may therefore have no greater significance than the measurement of plasma triglyceride levels in predicting a risk of cardiovascular disease.

The effect of phospholipase C on plasma factor VII.

The proposed link between a circulating factor VII-phospholipid complex and the risk of cardiovascular disease (CVD) has stimulated us to investigate the effect of phospholipase C (PLC) on the factor VII (FVII) activity in plasma from healthy individuals. PLC caused a rapid fall in FVII activity which was larger with heparinized than with citrated plasma. EDTA inhibited the PLC effect so emphasizing the involvement of divalent cations. PLC dependent loss of FVII activity varied widely between individuals, showed a highly significant correlation with plasma triglyceride concentrations, and was always greater in post-prandial compared to fasting plasma samples. Experiments using pure recombinant FVIIa and plasma depleted of FVII by adsorption indicated that loss of FVII activity only occurred in the simultaneous presence of absorbed plasma, FVIIa and PLC. Preincubation of PLC with adsorbed plasma before adding FVIIa did not lead to loss of FVII activity. It appears that PLC may act on lipoproteins already bound to FVII, in order to inhibit FVII activity. Other results indicated that competition between different plasma components (lipoproteins) in binding to FVII may govern the extent of the PLC dependent reduction in FVII activity.