Interventions to reduce ambient air pollution and their effects on health: An abridged Cochrane systematic review.

BACKGROUND: A broad range of interventions have been implemented to improve ambient air quality, and many of these have been evaluated. Yet to date no systematic review has been conducted to identify and synthesize these studies. In this systematic review, we assess the effectiveness of interventions in reducing ambient particulate matter air pollution and improving adverse health outcomes. METHODS: We searched a range of electronic databases across multiple disciplines, as well as grey literature databases, trial registries, reference lists of included studies and the contents of relevant journals, through August 2016. Eligible for inclusion were randomized and cluster randomized controlled trials, as well as several non-randomized study designs often used for evaluating air quality interventions. We included studies that evaluated interventions targeting industrial, residential, vehicular and multiple sources, with respect to their effect on mortality, morbidity and the concentrations of particulate matter (PM - including PM10, PM2.5, coarse particulate matter and combustion-related PM), as well as several criteria pollutants, including ozone, carbon monoxide, nitrogen oxides, nitrogen dioxide, nitric oxide and sulphur dioxide. We did not restrict studies based on the population, setting or comparison. Two authors independently assessed studies for inclusion, extracted data and assessed risk of bias. We assessed risk of bias using the Graphic Appraisal Tool for Epidemiological studies (GATE) for correlation studies, as modified and employed by the UK National Institute for Health and Care Excellence. We synthesized evidence narratively, as well as graphically using harvest plots. We assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. RESULTS: We included 42 studies assessing 38 unique interventions. These comprised a heterogeneous mix of interventions, including those aiming to address industrial sources (n = 5; e.g. the closure of a factory), residential sources (n = 7; e.g. coal ban), vehicular sources (n = 22; e.g. low emission zones), and multiple sources (n = 4; e.g. tailored measures that target both local traffic and industrial polluters). Evidence for effectiveness was mixed. Most included studies observed either no significant association or an association favoring the intervention, with little evidence that the assessed interventions might be harmful. CONCLUSIONS: Given the heterogeneity across interventions, outcomes, and methods, it was difficult to derive overall conclusions regarding the effectiveness of interventions in terms of improved air quality or health. Some evidence suggests that interventions are associated with improvements in air quality and human health, with very little evidence suggesting interventions were harmful. The evidence base highlights the challenges related to establishing the effectiveness of specific air pollution interventions on outcomes. It also points to the need for improved study design and analysis methods, as well as more uniform evaluations. The prospective planning of evaluations and an evaluation component built into the design and implementation of interventions may also be particularly beneficial.

Organ-specific responses during brain death: increased aerobic metabolism in the liver and anaerobic metabolism with decreased perfusion in the kidneys.

Hepatic and renal energy status prior to transplantation correlates with graft survival. However, effects of brain death (BD) on organ-specific energy status are largely unknown. We studied metabolism, perfusion, oxygen consumption, and mitochondrial function in the liver and kidneys following BD. BD was induced in mechanically-ventilated rats, inflating an epidurally-placed Fogarty-catheter, with sham-operated rats as controls. A 9.4T-preclinical MRI system measured hourly oxygen availability (BOLD-related R2*) and perfusion (T1-weighted). After 4 hrs, tissue was collected, mitochondria isolated and assessed with high-resolution respirometry. Quantitative proteomics, qPCR, and biochemistry was performed on stored tissue/plasma. Following BD, the liver increased glycolytic gene expression (Pfk-1) with decreased glycogen stores, while the kidneys increased anaerobic- (Ldha) and decreased gluconeogenic-related gene expression (Pck-1). Hepatic oxygen consumption increased, while renal perfusion decreased. ATP levels dropped in both organs while mitochondrial respiration and complex I/ATP synthase activity were unaffected. In conclusion, the liver responds to increased metabolic demands during BD, enhancing aerobic metabolism with functional mitochondria. The kidneys shift towards anaerobic energy production while renal perfusion decreases. Our findings highlight the need for an organ-specific approach to assess and optimise graft quality prior to transplantation, to optimise hepatic metabolic conditions and improve renal perfusion while supporting cellular detoxification.

A multidisciplinary approach to determine factors associated with calf rearing practices and calf mortality in dairy herds.

In the Netherlands, an increase in ear-tagged calf mortality (3 days to 1 year of age) in dairy farms was observed. The aim was to determine why calf mortality increased and how to reduce calf mortality in herds with structural high rates. A multi-disciplinary approach was chosen to study this phenomenon. First analysis of census data revealed that the majority of the calves died in the first month of life. In addition, a panel of 236 farmers indicated that the increase in calf mortality might be related to priority, time management and the mind-set of farmers. For that reason a questionnaire was carried out to detect risk factors for mortality among young calves (<1 month) in 100 dairy farms with increased calf mortality compared to 100 dairy farms with stable and below average calf mortality. The results showed that, besides management factors such as IBR and BVDV control, and purchase of cattle, also the answers to statements giving an indication on the farmers' mind-set, were associated with calf mortality. Therefore, a qualitative sociological study on the farmers' identity was conducted by performing in-depth interviews among 30 farmers with structurally high calf mortality rates. Afterwards, the results were communicated with a veterinary advisor who visited the farmers and gave tailored advice. Most of the interviewed farmers believed to have sufficient knowledge and skills regarding calf rearing. The farmers did not share their calf rearing problems with colleagues and advisors but they mentioned to be open to receive advice if not communicated in a reproaching or pedantic way. The sociologist distinguished three different phases of awareness concerning calf mortality among the farmers: (1) farmers who were only partly, or not at all, aware of high calf mortality; (2) farmers who felt powerless because of their inability to find a solution to their problems; and (3) farmers who knew they can be inaccurate when it comes to rearing calves, but were reluctant to change this. With the background information of the farmers' identity it was easier for the veterinary advisor to provide tailored advice resulting in a higher probability of following up. A first evaluation in which calf mortality rates in the six months after providing the advice were monitored, indicated that the advice resulted in reduced mortality. The combination of census data, epidemiological and qualitative sociological research revealed that advisors should be aware of the attitude and mind-set of the farmer and adapt their approach and advice accordingly.

Exogenous application of platelet-leukocyte gel during open subacromial decompression contributes to improved patient outcome. A prospective randomized double-blind study.

BACKGROUND: Platelet-leukocyte gel (PLG) is being used during various surgical procedures in an attempt to enhance the healing process. We studied the effects of PLG on postoperative recovery of patients undergoing open subacromial decompression (OSD). METHODS: PLG was produced from platelet-leukocyte-rich plasma (P-LRP), prepared from a unit of whole blood. Forty patients were included in the study. Self-assessed evaluations, using the American Shoulder and Elbow Surgeons scoring system of activities of daily living (ADL), joint instability, pain levels, pain medications, and clinical evaluations for range of motion were conducted. RESULTS: Platelet and leukocyte counts were significantly increased in the P-LRP compared to baseline counts. Treated patients demonstrated decreased visual analog scales for pain and used significantly less pain medication, had an improved range of motion during passive forward elevation, external rotation, external rotation with arm at 90 degrees abduction, internal rotation, and cross body adduction compared to control patients (p < 0.001). No differences in the instability score were observed between the groups. Furthermore, treated patients performed more ADL (p < 0.05). CONCLUSION: In the PLG-treated group, recovery was faster and patients returned earlier to daily activities and also took less pain medication than control subjects.

Accumbal dopamine and serotonin in anticipation of the next aggressive episode in rats.

Autonomic and limbic neural activities are linked to aggressive behavior, and it is hypothesized that activities in the cardiovascular and monoaminergic systems play a role in preparing for an aggressive challenge. The objective was to learn about the emergence of monoamine activity in nucleus accumbens before an aggressive confrontation that was omitted at the regular time of occurrence, dissociating the motoric from the aminergic activity. Dopamine, serotonin, heart rate and behavioral activity were monitored before, during and after a single 10-min confrontation in resident male Long-Evans rats fitted with a microdialysis probe in the n. accumbens and with a telemetry sender (experiment 1). DA, but not 5-HT efflux, was confirmed to increase in n. accumbens during and after a single aggressive episode. In aggressive males that confronted an opponent daily for 10 days (experiment 2) heart rate rose 1 h before the regularly scheduled encounter relative to control rats, as measured on day 11 in the absence of any aggression. Concurrently, DA levels increased by 60-70% over baseline levels and 5-HT levels decreased by 30-35% compared to baseline levels. These changes were sustained over 1 h, and contrasted with no significant changes in DA, 5-HT, heart rate or behavioral activity in control rats. The rise in mesolimbic DA appears to be significant in anticipating the physiological and behavioral demands of an aggressive episode, and the fall in 5-HT in its termination, dissociated from the actual execution of the behavior.

Short or continuous social stress: suppression of continuously available ethanol intake in subordinate rats.

We explored the effects of short, intermediate, and continuous social stress on daily ethanol and water intake in rats. The study was designed to: (1) detect increases in intake during hours when animals were not stressed; and (2) detect shifts in preference from solutions with high to low alcohol content. Male Long-Evans rats acquired ethanol self-administration using a sucrose-fading procedure, which was followed by continuous access to 10% and 3% ethanol solutions and water. After intake stabilized, rats were exposed to three periods of five consecutive days of social stress, with 8-10 days without stress in between. Short social stress consisted of being attacked and defeated by an aggressive opponent, followed by 30 min exposure to threats by the aggressive male while in a protective cage. Intermediate and continuous social stress consisted of a 6 h or 24 h 'threat of attack' exposure, respectively. All stress exposures reduced daily intake of 10% ethanol, did not cause changes in intake of 3% ethanol, and caused increases in water intake. No compensatory ethanol consumption was observed on stress days or after stress exposure was discontinued. These results are at variance with the hypothesis for increased alcohol consumption during or following social stress episodes.

Persistent suppression of ethanol self-administration by brief social stress in rats and increased startle response as index of withdrawal.

Excessive alcohol drinking is often linked to the experience of stress, but experimental approaches using animal models of alcohol self-administration have had widely varying outcomes. The objective was to determine how daily exposure to brief, predictable social stress would change alcohol self-administration in rats in a daily limited access protocol. Male Long-Evans rats had either access to a 10% ethanol solution for 15 min in the home cage setting (n=20) or were reinforced with 15% ethanol deliveries for every fifth lever press (n=10). Subsequently, all rats were subjected to brief social stress for five consecutive days. Social stress consisted of attacks by an opponent for 5 min followed by exposure to threats while in a protective cage for 30 min. In both the home cage drinking and operant conditioning groups, social stress exposure significantly decreased alcohol intake or rate of alcohol reinforcements, respectively. When alcohol intake was scheduled immediately before social stress (i.e., 24 h after the previous social stress episode), a decrease was observed with a delay of 1 or 2 days. When alcohol intake was scheduled 4 h after stress, no changes in intake or alcohol reinforcements were observed. Animals that consumed a low dose of ethanol displayed less defensive behavior during social stress compared to water-drinking animals, and showed an increased startle reflex at 8 and 56 h after discontinuation of daily ethanol access. The current experimental protocols of social defeat stress reveal a transient suppression rather than a facilitation of alcohol consumption.

Aggressive behavior, increased accumbal dopamine, and decreased cortical serotonin in rats.

Dopamine (DA) and serotonin have been implicated in the regulation of aggressive behavior, but it has remained challenging to assess the dynamic changes in these neurotransmitters while aggressive behavior is in progress. The objective of this study was to learn about ongoing monoamine activity in corticolimbic areas during aggressive confrontations in rats. Male Long-Evans rats were implanted with a microdialysis probe aimed at the nucleus accumbens (NAC) or medial prefrontal cortex (PFC); next, 10 min samples were collected before, during, and after a 10 min confrontation. Rats continued to display aggressive behavior while being sampled, and they performed two to six attack bites as well as 140 sec of aggressive acts and postures. Dopamine levels in NAC were significantly increased up to 60 min after the confrontation. Peak levels of 140% were achieved approximately 20-30 min after the confrontation. No concurrent changes in accumbal serotonin levels were seen during or after the confrontation. Dopamine and serotonin levels in PFC changed in the opposite direction, with a sustained decrease in serotonin to 80% of baseline levels during and after the confrontation and an increase in dopamine to 120% after the confrontation. The temporal pattern of monoamine changes, which followed rather than preceded the confrontation, points to a significant role of accumbal and cortical DA and 5-hydroxytryptamine in the consequences as opposed to the triggering of aggressive acts. The increase in accumbal DA in aggressive animals supports the hypothesis that this neural system is linked to the execution of biologically salient and demanding behavior.

d-amphetamine "cue" generalizes to social defeat stress: behavioral sensitization and attenuated accumbens dopamine.

RATIONALE: Psychomotor stimulant drugs engender intense euphoria as well as anxiogenic effects, both potentially involving the mesolimbic dopamine system. OBJECTIVES: (1) Do animals that discriminate a psychomotor stimulant drug from saline generalize to a non-pharmacological stressful event such as social defeat? (2) How does the generalization from d-amphetamine to social defeat stress relate to dopamine overflow in the mesocorticolimbic system in response to this stress? METHODS: Adult male Long-Evans rats were trained to discriminate either 1.0 mg/kg d-amphetamine or 10 mg/kg cocaine from saline in a two-lever drug discrimination task; each injection-appropriate tenth lever press was reinforced by milk presentation (fixed ratio, FR10). After confirming systematic cocaine and d-amphetamine dose-effect curves, additional discrimination tests involved exposure to several stress conditions; (1) brief confrontations with an aggressive resident rat that resulted in the intruder's defeat. Rats were administered saline, then exposed to aggressive threats behind a protective screen for 15 min, and subsequently performed the two-lever discrimination task; (2) exposure for 15 min to aggressive threats without prior defeat; (3) exposure to a novel cage for 15 min. A subgroup of rats was prepared for in vivo microdialysis after they generalized the social stress response to the d-amphetamine cue. RESULTS: Nine of 35 d-amphetamine-trained and six of 18 cocaine-trained animals responded at least 80% at the drug-appropriate lever after social defeat stress. Social defeat stress increased dopamine in nucleus accumbens, with a closely similar dopamine response in amphetamine-discriminating rats that were behaviorally sensitized versus those that were not sensitized by amphetamine. CONCLUSIONS: Generalization from social stress to the stimulant "cue" differs among individuals, which may be relevant to the anxiety-like effects of stimulants. By contrast, mesolimbic DA activity and motor activity was increased in response to social defeat stress or a d-amphetamine challenge, regardless of the qualitatively different stimulant-stress generalization. Mesolimbic DA in response to stress or amphetamine appears significant in behavioral activation, but not in the qualitatively divergent internal stimulus properties.

Effect of genetic variants of the heart fatty acid-binding protein gene on intramuscular fat and performance traits in pigs.

In order to find genetic markers to improve the meat quality of pigs by breeding we studied the relationship between variation in the heart fatty acid-binding protein (H-FABP) gene (FABP3) and intramuscular fat (IMF) content. To estimate the effect of H-FABP, pigs from two Duroc populations were selectively mated in such a way that at least two genotypes were present in each litter. In total, data from 983 pigs and pedigree information from three preceding generations were analyzed. Offspring were tested for IMF content as well as backfat thickness (BFT), BW, and drip loss of the meat (DRIP). All pigs were assigned to H-FABP RFLP genotype classes either by the assessed genotype (75%) or based on a probability score determined according to genotypic information of their relatives (25%). Contrasts were detected between homozygous H-FABP RFLP genotype classes for IMF content (.4%, P < .05), BFT (.6 mm, P < .01), and BW (2.4 kg, P < .10). No significant contrasts were detected for DRIP. Results for IMF content, BFT, and BW were confirmed when only genotyped animals were analyzed. Variation in BFT partially explained the effect on IMF content. Although other closely linked genes on porcine chromosome 6 might be responsible for the observed effect, interference of the halothane gene was excluded because all parental animals were noncarriers. In conclusion, H-FABP RFLP can be used as markers to select for increased IMF content and growth in breeding programs.

The adipocyte fatty acid-binding protein locus: characterization and association with intramuscular fat content in pigs.

The porcine A-FABP gene (FABP4) was isolated and sequenced to study the role of A-FABP in the differentiation of intramuscular fat (IMF) accretion in pigs. The coding sequence of the porcine A-FABP gene is highly conserved across human, mouse, and rat. Moreover, all the functionally important amino acids are conserved. This high similarity extends into the first 270 bp of the 5' upstream region. Within this region, a 56-bp nucleotide sequence was completely identical with the corresponding sequence in the mouse A-FABP gene, which contains the transcription factor binding sites for C/EBP and AP-1, and is implicated in the differentiation-dependent regulation of A-FABP. The A-FABP gene was assigned to porcine Chromosome (Chr) 4 by a porcine sequence-specific PCR on a cell hybrid panel, fully consistent with comparative mapping data with human and mouse. In the first intron of the porcine A-FABP gene, a microsatellite sequence was detected that was polymorphic for all six pig breeds tested. This genetic variation within the A-FABP gene was associated with differences in IMF content and possibly growth in a Duroc population, whereas no effect on backfat thickness and drip loss of the meat were detected. A considerable and significant contrast of approximately 1% IMF was observed between certain genotype classes. We conclude that the A-FABP locus is involved in the regulation of intramuscular fat accretion in Duroc pigs.

The hypothalamus: cross-roads of endocrine and behavioural regulation in grooming and aggression.

Anatomical and functional studies show that the hypothalamus is at the junction of mechanisms involved in the exploratory appraisal phase of behaviour and mechanisms involved in the execution of specific consummatory acts. However, the hypothalamus is also a crucial link in endocrine regulation. In natural settings it has been shown that behavioural challenges produce large and fast increases in circulating hormones such as testosterone, prolactin, corticotropin and corticosterone. The behavioural function and neural mechanisms of such fast neuroendocrine changes are not well understood. We suggest that behaviourally specific hypothalamic mechanisms, at the cross-roads of behavioural and endocrine regulation, play a role in such neuroendocrine changes. Mild stimulation of the hypothalamic aggressive area, produces stress levels of circulating prolactin, corticotropin, and corticosterone. Surprisingly luteinizing hormone does not change. This increase in stress hormones is due to the stimulation itself, and not caused by the stress of fighting. Similar increases in corticosterone are observed during electrical stimulation of the hypothalamic self-grooming area. The corticosterone response during self-grooming-evoking stimulation is negatively correlated with the amount of self-grooming observed, suggesting that circulating corticosterone exerts a negative feedback control on grooming. Earlier literature, and preliminary data form our laboratory, show that circulating corticosterone exerts a fast positive feedback control over brain mechanisms involved in aggressive behaviour. Such findings suggest that the hormonal responses caused by the activity of behaviourally specific areas of the hypothalamus may be part of a regulation mechanism involved in facilitating or inhibiting the very behavioural responses that can be evoked from those areas. We suggest that studying such mechanisms may provide a new approach to behavioural dysfunctions associated with endocrine disorders and stress.

Identifying cytologic characteristics and grading endocervical columnar cell abnormalities. A study aided by high-definition television.

OBJECTIVE: To test the ability of cytotechnologists to recognize and accurately interpret selected architectural, cellular and nuclear features presented on a high-definition television (HDTV) and to make a reliable diagnosis with HDTV. STUDY DESIGN: A total of 1,122 features considered diagnostic of different endocervical columnar cell abnormalities were selected from 50 smears from 48 women with the help of a motor-driven-stage microscope by five observers who had knowledge of the final diagnosis. The selected and stored features were presented on an HDTV and evaluated in five successive sessions without knowledge of the final diagnosis. RESULTS: Specific types of features were correctly identified in a high number of cases. Considerable interobserver variability was demonstrated in the scoring of grades of expression of features. Overrated and under-rated monitor diagnoses were related to overvalued and undervalued features. From a group of 437 images that were correctly diagnosed by four or five observers, five features proved to be highly related to the correct diagnosis. CONCLUSION: Observers were capable of making a reliable diagnosis on features, selected by other observers, when presented on an HDTV. An overall correct diagnosis was made in 93% of cases.

Increased aggression after ethanol self-administration in male resident rats.

In order to study experimental alcohol intake that leads to heightened aggression, we established ethanol self-administration in aggressive rats. The focus was on low doses of self-administered ethanol and to assess their effects on aggressive behavior in resident rats, using a limited access paradigm followed by a 5-min confrontation with an intruder. In the first phase of the experiment, rats were established as "residents", and their consistent aggressive behavior in confrontations with an intruder was verified. In the second phase, these resident rats were trained to self-administer alcohol, using a sucrose-fading technique. In the third phase, alcohol self-administration was followed by intruder confrontations in order to study the effect of alcohol on aggression. Confrontations after ethanol consumption leading to low (5-20 mg/dl) and moderate (20-50 mg/dl) blood alcohol concentration (BAC) were compared to confrontations without alcohol, each animal serving as its own control. On average, the group showed no change in aggressive behavior after low or moderate ethanol intake. However, six out of 16 individuals significantly increased the number of attack bites and the duration of aggressive behavior by up to 90% after alcohol self-administration. When these rats were assigned post-hoc to an alcohol heightened aggression group, the group was characterized by a 40% increase in number of attack bites and a 90% increase in aggressive posture over control (BAC 0 mg/dl), whereas the alcohol non-heightened aggression group showed no significant changes. These results extend previous observations of increased aggression in a subpopulation of animals after experimenter-administered ethanol in mice, rats and monkeys to self-administered alcohol. Using this animal model, individuals showing enhanced or reduced aggression after oral alcohol self-administration can be characterized behaviorally, physiologically, and neurochemically.

Alcohol, GABAA-benzodiazepine receptor complex, and aggression.

Neurobiological investigations have become productive since experimental protocols were developed that engender large increases in aggressive behavior after acute alcohol challenges in individual experimental animals. Recent developments extended the heightened aggressive behavior to rats that self-administered alcohol shortly before the social confrontation. Quantitative ethological analysis revealed that alcohol prolongs "bursts" of aggressive acts and displays and disrupts communication between the aggressive animal and the opponent who defends, submits, or flees. Pharmacological modulation of the GABAA receptor with benzodiazepine agonists and neuroactive steroids results in dose-dependent biphasic changes in aggressive behavior that mimic the dose-effect function of alcohol; benzodiazepines potentiate the aggression-heightening effects of alcohol as well as the behaviorally suppressive effects; and antagonists at benzodiazepine receptors prevented the aggression-heightening effects of alcohol. The maturational and experiential origins for potentially distinctive GABAA receptor characteristics in individuals who exhibit heightened aggressive behavior await identification.

Individual use of cytomorphologic characteristics in the diagnosis of endocervical columnar cell abnormalities: selection of preferred features with help of the 'Navigator' microscope.

In our previous interobserver studies on endocervical columnar cell abnormalities, we studied architectural, cellular and nuclear features in cervical smears of women known to have columnar cell atypias of variable severity, to determine cytomorphologic criteria, discriminating between mild, moderate and severe intraepithelial columnar cell lesions and adenocarcinoma. The results of these studies revealed a number of architectural, cellular and nuclear characteristics in different grades of expression, which were of importance for the primary diagnosis of: no abnormalities, different grades of intraepithelial endocervical columnar cell lesions and adenocarcinoma. Furthermore we concluded that observers used different characteristics and different grades of expression of these characteristics for comparable diagnoses. The present study was undertaken to determine those features, which were considered discriminating by each individual for the diagnosis of mild, moderate and severe atypia, adenocarcinoma in situ and adenocarcinoma. Features selected by five observers with knowledge of the final diagnosis, were stored and reviewed with help of a motor driven stage ('Navigator')-microscope and a high definition television-monitor. The results confirmed individual observer variability in the number and type of features used in the diagnosis of endocervical columnar cell abnormalities. Features such as 'variation in nuclear size and shape', 'irregular chromatin distribution' and 'coarsely granular chromatin' were selected preferentially by all observers in the diagnosis of endocervical columnar cell lesions, conversely striking differences were observed in the application of 'architectural'-and, especially in cases of 'adenocarcinoma', 'nucleolar' characteristics.

Endocervical columnar cell intraepithelial neoplasia (ECCIN). 3. Interobserver variability in feature use.

In our previous studies on endocervical columnar cell abnormalities, the ability of 5 cytotechnicians was tested to distinguish between cases of: no abnormalities, different grades of intraepithelial endocervical columnar cell atypias and invasive adenocarcinoma. On the basis of stepwise multiple regression analysis, nuclear chromatin distribution, variation in cellular and nuclear size, cytoplasmic eosinophilia and architectural features such as cell-crowding, cluster formation, formation of gland-like structures and pseudostratification appeared to be of primary diagnostic importance to discriminate between no abnormalities, different grades of cervical columnar cell atypias, adenocarcinoma in situ and adenocarcinoma. The present paper reports the results of a study which was designed to assess the individual performance in feature use and classification of endocervical lesions. The results of this study indicate that observers use different characteristics and different grading for the level of expression of these characteristics. However, all observers illustrated a strong relationship between the presence and the expression grade of a certain feature and the degree of endocervical columnar cell atypia. With acceptance of one grade of difference in grades of severity, an overall correct diagnosis was made in 87.6% of cases (range 80-98.2%).

CytosafePLUS. A workstation for screening, supervision, reviewing, quality assurance and education in cytopathology.

In pathology, the subjective cytologic and histologic diagnosis suffers from large observer variability. Effective methods of reducing the effects of this observer variability in cytologic diagnosis are close supervision of the diagnostic process and multiple screening by different observers of cases that have a higher risk of abnormalities as well as closely supervised follow-up procedures for early lesions. Accurate supervision of screening completeness has become possible with the development of computer programs and microscope instrumentation to register the path of the objective over the slide and therefore the fields that have been inspected by the screener (Axio-Home, Carl Zeiss, Oberkochen, Germany; Navigator, Becton Dickinson Cellular Imaging Systems, Leiden, the Netherlands). Based on these technologies, all objects of interest on the microscope slide are marked electronically, and the X,Y coordinates of these marks are stored in the computer. With these coordinates, a motor-driven microscope stage can be redirected to the selected objects, enabling the observer to quickly review the objects. The reviewer can thus reinspect cells or groups of cells, previously identified, in a much more accurate way than is presently possible, by marking objects of interest with ink dots. To these marked objects, specific diagnoses can be attached, as can comments or questions, which are also stored in the computer and are made part of the cytology report. After analysis, all marked objects can be relocated automatically with the help of the computer-directed microscope stage. Using this concept, a subsequent observer or a supervisor can easily and effectively reply to the remarks attached to these objects. It is also possible to reedit the comments made or to attach answers to specific questions. In an interobserver study, encompassing 50 cases of columnar cell abnormalities screened by five observers using the Navigator microscope stage and software, it proved possible to reduce reviewing time significantly. On the basis of marked cytologic characteristics discriminating cellular features in the diagnosis, endocervical columnar abnormalities could be identified. The coordinates of the objects of interest are made part of the laboratory record of the cytology findings (Cytosafe, Omnisys, Hoevelaken, the Netherlands). This development largely facilitates the review of previous findings when evaluating follow-up specimens. With the use of a Navigator motor-driven stage and CCD camera, microscope images can be made of the specimen under study. These images can be stored in the computer in a digitized format, labeled with their X,Y coordinates on the specimen. The CytosafePLUS workstation, encompassing the Navigator automated cell positioning system and CCD attachment, is a highly effective tool in cytologic screening, reviewing and reporting, in surveillance of follow-up, in intralaboratory and interlaboratory consultation, in cytology training, in proficiency testing and in quality assurance.

A time-structured analysis of hypothalamically induced increases in self-grooming and activity in the rat.

Stressors and different manipulations of the paraventricular nucleus of the hypothalamus (PVH) increase self-grooming in the rat. To assess the effect of these PVH manipulations on the timing of grooming in relation to other ongoing behavior, the authors describe these behavioral responses by a time-structured model. The authors show the following: (a) Behavior in each treatment group can be described by a semi-Markov model. Effects of treatments can be described as changes in the parameters of this model, which reflect the tendencies to start and stop grooming and other activities. (b) The PVH manipulations increase self-grooming by increasing the tendencies to start grooming or by extending the period during which grooming occurs. (c) Grooming responses are accompanied by an increase in activity. (d) Different PVH manipulations change the temporal structure of behavior differentially, suggesting that distinct mechanisms within the PVH are involved in the precise timing of grooming in relation to other activities.

Endocervical columnar cell intraepithelial neoplasia. II. Grades of expression of cytomorphologic criteria.

OBJECTIVE: To determine the relationship between the grade of expression of discriminating cytomorphologic architectural, cellular and nuclear features and the degree of endocervical columnar cell atypia. STUDY DESIGN: The study group consisted of 55 smears from 53 women known to have endocervical columnar cell atypias of variable severity. The smears were reviewed by five observers by means of 46 architectural, cellular and nuclear features. Seventeen of the 46 evaluated features were scored as revealing three grades of expression: slight, moderate and marked. RESULTS: Grades of expression of cellular and nuclear characteristics used in the evaluation of endocervical columnar cell abnormalities were identical to the characteristics used in the diagnosis of squamous (metaplastic) lesions. As such the features were extremely useful, with the exception of hyperchromasia, which was less prominently expressed. Furthermore, the results on architectural features revealed that the expression grades slight and moderate were indicative of mild and moderate endocervical columnar cell atypia, whereas the marked expression grade was strongly related to the severe intraepithelial lesions and adenocarcinoma. CONCLUSION: Characteristic cytomorphologic features at different grades of expression proved to be reliable light microscopic parameters in the diagnosis of different grades of endocervical columnar cell abnormalities. The accuracy of diagnosis at least equaled that of detecting squamous (metaplastic) lesions.