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Spatiotemporal dynamics of charged species in the afterglow of plasmas containing negative ions.

The spatiotemporal evolution of charged species densities and wall fluxes during the afterglow of an electronegative discharge has been investigated. The decay of a plasma with negative ions consists of two stages. During the first stage of the afterglow, electrons dominate plasma diffusion and negative ions are trapped inside the vessel by the static electric field; the flux of negative ions to the walls is nearly zero. During this stage, the electron escape frequency increases considerably in the presence of negative ions, and can eventually approach free electron diffusion. During the second stage of the afterglow, electrons have disappeared, and positive and negative ions diffuse to the walls with the ion-ion ambipolar diffusion coefficient. Theories for plasma decay have been developed for equal and strongly different ion (T(i)) and electron (T(e)) temperatures. In the case T(i)=T(e), the species spatial profiles are similar and an analytic solution exists. When detachment is important in the afterglow (weakly electronegative gases, e.g., oxygen) the plasma decay crucially depends on the product of negative ion detachment frequency (gamma(d)) and diffusion time (tau(d)). If gamma(d)tau(d)>2, negative ions convert to electrons during their diffusion towards the walls. The presence of detached electrons results in "self-trapping" of the negative ions, due to emerging electric fields, and the negative ion flux to the walls is extremely small. In the case T(i)<<T(e), the spatiotemporal dynamics is more complicated due to the presence of negative ion density fronts. During the afterglow, although negative ions diffuse freely in the plasma core, the negative ion fronts propagate towards the chamber walls with a nearly constant velocity. The evolution of ion fronts in the afterglow of electronegative plasmas is important, since it determines the time needed for negative ions to reach the wall, and thus influence surface reactions in plasma processing.

Journal Article↗

Effects of changes of ionic environment on the negative after-potential of the spike in rat uterine muscle.

1. The spontaneous activity of the smooth muscle of rat uterus consists of bursts of spikes, each spike being followed by a negative after-potential. The effect of changes in ionic environment on the negative after-potential was investigated at various stages of pregnancy and in the non-pregnant condition.2. The amplitude of the negative after-potential was the same in spontaneously generated and electrically evoked spikes. During repetitive discharge, whether spontaneous or in response to depolarizing current application, the amplitude of the after-potential was smallest in the first spike of a burst and it increased gradually with repetition of discharge.3. The decay of the negative after-potential was slower than the passive return of the membrane potential to its resting level.4. The amplitude of the negative after-potential was larger in non-pregnant uterus than during late pregnancy.5. In pregnant uterus, the replacement of the Cl in the medium with benzene sulphonate transiently augmented the negative after-potential and then gradually reduced it. Eventually, the negative after-potential disappeared and, instead, a positive after-potential was observed. This conversion took place without a noticeable change in the resting potential or in the initial falling phase of the action potential itself. Replacement of Cl with NO(3) had no appreciable effect on the negative after-potential.6. In non-pregnant uterus, the conversion of the negative to a positive after-potential was never observed. However, in Cl-deficient solution the size and duration of the negative after-potential were reduced.7. In Cl-deficient solution (benzene sulphonate substitution), the decay of the electrotonic potential following the break of cathodal current became faster than that in normal solution. On the other hand the development of the anodic electrotonic potential became slower.8. Replacement of the NaCl in the medium with sucrose converted the negative after-potential to a positive after-potential. On the other hand, reduction of Na only by replacement of NaCl with Tris-Cl had no noticeable effect on the negative after-potential.9. It is concluded that the negative after-potential of the spike in rat uterine muscle is largely due to an increase of Cl conductance of the membrane.

Action Potentials↗

Evaluation of negation phrases in narrative clinical reports.

OBJECTIVE: Automatically identifying findings or diseases described in clinical textual reports requires determining whether clinical observations are present or absent. We evaluate the use of negation phrases and the frequency of negation in free-text clinical reports. METHODS: A simple negation algorithm was applied to ten types of clinical reports (n=42,160) dictated during July 2000. We counted how often each of 66 negation phrases was used to mark a clinical observation as absent. Physicians read a random sample of 400 sentences, and precision was calculated for the negation phrases. We measured what proportion of clinical observations were marked as absent. RESULTS: The negation algorithm was triggered by sixty negation phrases with just seven of the phrases accounting for 90% of the negations. The negation phrases received an overall precision of 97%, with "not" earning the lowest precision of 63%. Between 39% and 83% of all clinical observations were identified as absent by the negation algorithm, depending on the type of report analyzed. The most frequently used clinical observations were negated the majority of the time. CONCLUSION: Because clinical observations in textual patient records are frequently negated, identifying accurate negation phrases is important to any system processing these reports.

Algorithms↗

[Left ventriculography and serial ECG changes in hypertrophic cardiomyopathy with special reference to the negative T wave].

To clarify the correlation between the configuration of the left ventriculogram and serial ECG changes, 16 patients with hypertrophic cardiomyopathy (HCM) associated with asymmetrical septal hypertrophy were examined. In the right oblique view at end-diastole, the configurations were classified by form as round (R, n = 7), round with inferior concavity (R-i, n = 2), spade (S, n = 4) and spade with inferior concavity (S-i, n = 3). These patients were divided into two groups according to serial T wave changes; nine with marked changes (A group) and seven without (B group). Furthermore, group A was separated into two subgroups; seven with increasing negativity or appearance of the negative T wave (A-1 group) and two with decreasing negativity or disappearance of the negative T wave (A-2 group). The results were as follows: Five (71%) of the seven cases with the S and S-i form belonged to the A group. Their apical walls showed marked hypertrophy and their ECGs showed deep negative T waves. The other two cases (29%) belonged to the B group, and did not show marked apical hypertrophy. Four (44%) of the nine cases with the R and R-i form belonged to the A group. They showed mild apical hypertrophy, and initially did not show deep negative T waves. A deep negative T wave appeared in three during observation. The initial depth of the maximum negativity of T wave correlated significantly with apical wall thickness, SV1 + RV5, and the total depth of the negative T wave in precordial leads. During the observation, the A-1 group showed a marked increase of SV1 + RV5. The A-2 group showed a decrease of SV1 + RV5. In conclusion, HCM with deep negative T waves has a tendency to present wide changes in the T wave during serial ECG observation and to show apical hypertrophy on left ventriculography. Cases of increasing negativity of the T wave showed marked increase in voltage of SV1 + RV5. However, cases of decreasing negativity of the T wave showed decreasing SV1 + RV5. These ECG changes, especially the negative T wave changes are reputed to be related to apical wall thickness.

Cardiomyopathy, Hypertrophic↗

The negative predicative value of breast fine-needle aspiration biopsy: the Massachusetts General Hospital experience.

Breast fine-needle aspiration biopsy (FNAB) has been increasingly accepted as an important triage tool for the evaluation of breast lumps. We examined the clinical utility and diagnostic accuracy of a negative breast FNAB result by studying 450 breast aspirates in 413 patients (average age 45 years) with a "negative" or benign cytologic interpretation performed at Massachusetts General Hospital over a 4-year period. Of these patients, 121 (29%) underwent subsequent biopsy and 17 (4%) were found to have malignancy (3% of total negative FNABs; 14% with histology). None of these 17 patients had a triple negative test. A cohort of 115 patients had documentation of negative physical, radiologic, and cytologic examinations (the triple negative), none of whom were found to have malignancy on histologic or at least 2-year clinical follow-up (negative predictive value [NPV] = 100% with a triple-negative test). Outside of the triple-negative test, the NPV of a negative breast FNAB is reduced with a false-negative rate of 7%. However, in the setting of a triple-negative test, the NPV in our patient population was 100%, reassuring the patient and clinician that clinical follow-up and not surgical intervention was sufficient for proper patient care.

Adolescent↗

Risk factors for Gram-negative bacterial infections in febrile neutropenia.

BACKGROUND AND OBJECTIVES: The objective of this study was to evaluate the risk of Gram-negative bacterial infections in febrile neutropenic patients and to develop a specific risk score. DESIGN AND METHODS: This prospective study included 513 consecutive febrile neutropenic, evaluable patients. Forty-five per cent of the patients were receiving prophylactic gut decontamination, and 6% were receiving prophylactic quinolones at the onset of febrile neutropenia. Data were collected from the onset of febrile neutropenia until 30 days later. Risk factors for Gram-negative bacterial infection were identified by comparing baseline characteristics of patients with and without Gram-negative bacterial infection. Independent risk factors in multivariate analysis were used to build a predictive score for Gram-negative bacterial infection. RESULTS: The prevalence of Gram-negative bacterial infection was 55/513 (10.7%). Gram-negative bacterial infections were due to E. coli in 30 patients, other enterobacteriae in 11, Pseudomonas spp. in 13, and Salmonella spp. in one. In multivariate analysis, the occurrence of Gram-negative bacterial infection was significantly associated with age > 45 years (p=0.009), recent administration of betalactams (p=0.04), chills (p=0.0001), urinary symptoms (p=0.01), and absence of gut decontamination with both colimycin and aminoglycosides (p=0.001). The relative risk for Gram-negative bacterial infection was 4.4, 12.6, 25.4 and 100 in the presence of 1, 2, 3 , or at least 4 parameters, respectively. The performances of our scoring system and the post-test probabilities according to different prevalence rates of Gram-negative bacterial infection (0.05, 0.10, 0.20) lead us to propose a Gram-negative risk score of >or=3 as indicating a high probability of Gram-negative bacterial infection. INTERPRETATION AND CONCLUSIONS: Our scoring system identifies patients with a high probability of Gram-negative bacterial infection as those with a score >or=3. If confirmed in a validation set, this score could be considered in the choice of the first-line antibiotics in febrile neutropenic patients.

Adolescent↗

Anhedonia and negative symptomatology in chronic schizophrenia.

The relationships between negative symptomatology and anhedonia have been studied on 61 subjects who had Research Diagnostic Criteria for chronic schizophrenia. Negative symptomatology was rated by the negative subscales of the Kay Positive and Negative Syndrome Scale (PANSS) and of the Brief Psychiatric Rating Scale (BPRS). Anhedonia was rated by the Physical Anhedonia Scale of Chapman (PAS), the Fawcett-Clark Pleasure Capacity Scale-Physical Pleasure (FCPCS-PP), and the social interest subscale (SIS) of the Nurse Observation Scale for Inpatients (NOSIE-30). Pearson correlations were calculated between negative and anhedonia scales. Schizophrenics were dichotomized first into negatives and positives using the composite score of the PANSS, and second into low and high negatives using the negative subscale of the PANSS. For each dichotomy, the corresponding subgroups were compared on anhedonia scales using Student's test. The results have shown no significant correlations between negative and anhedonia scales (PAS and FCPCS-PP). There were no significant differences concerning the PAS and the FCPCS-PP between negative and positive subgroups of schizophrenics and between low- and high-negative subgroups. Anhedonia is not a negative symptom. Our results confirm the reported studies on subjective experiences in schizophrenia. A search for more restricted forms of schizophrenia characterized by severe anhedonia is needed.

Adult↗

Understanding 'not': neuropsychological dissociations between hand and head markers of negation in BSL.

Simple negation in natural languages represents a complex interrelationship of syntax, prosody, semantics and pragmatics, and may be realised in various ways: lexically, morphologically and prosodically. In almost all spoken languages, the first two of these are the primary realisations of syntactic negation. In contrast, in many signed languages negation can occur without lexical or morphological marking. Thus, in British Sign Language (BSL), negation is obligatorily expressed using face-head actions alone (facial negation) with the option of articulating a manual form alongside the required face-head actions (lexical negation). What are the processes underlying facial negation? Here, we explore this question neuropsychologically. If facial negation reflects lexico-syntactic processing in BSL, it may be relatively spared in people with unilateral right hemisphere (RH) lesions, as has been suggested for other 'grammatical facial actions' [Language and Speech 42 (1999) 307; Emmorey, K. (2002). Language, cognition and the brain: Insights from sign language research. Mahwah, NJ: Erlbaum (Lawrence)]. Three BSL users with RH lesions were specifically impaired in perceiving facial compared with manual (lexical and morphological) negation. This dissociation was absent in three users of BSL with left hemisphere lesions and different degrees of language disorder, who also showed relative sparing of negation comprehension. We conclude that, in contrast to some analyses [Applied Psycholinguistics 18 (1997) 411; Emmorey, K. (2002). Language, cognition and the brain: Insights from sign language research. Mahwah, NJ: Erlbaum (Lawrence); Archives of Neurology 36 (1979) 837], non-manual negation in sign may not be a direct surface realisation of syntax [Language and Speech 42 (1999) 143; Language and Speech 42 (1999) 127]. Difficulties with facial negation in the RH-lesion group were associated with specific impairments in processing facial images, including facial expressions. However, they did not reflect generalised 'face-blindness', since the reading of (English) speech patterns from faces was spared in this group. We propose that some aspects of the linguistic analysis of sign language are achieved by prosodic analysis systems (analysis of face and head gestures), which are lateralised to the minor hemisphere.

Aged↗

Analysis of mechanisms that determine dominant negative estrogen receptor effectiveness.

To analyze the mechanisms by which estrogen receptor (ER) activity is suppressed by dominant negative mutants, we examined the role of specific ER functions and domains in transcriptional repression. We previously described three transcriptionally inactive human ER mutants (the frameshift mutant S554fs, the point mutant L540Q, and the truncated receptor ER1-530), which act as effective dominant negative mutants, inhibiting the activity of wild type ER when they are coexpressed in mammalian cells. After additional mutational modifications, the ability of the ER mutants to suppress the activity of wild type ER was analyzed in cotransfection assays of the dominant negative mutants and wild type ER and an estrogen-responsive reporter gene (2ERE-TATA-CAT or 2ERE-pS2-CAT). Eliminating the ability of the three dominant negative mutants to bind to estrogen response element (ERE) DNA (by introducing three point mutations in their DNA binding domains) dramatically reduced, but did not completely abolish, the dominant negative activity of the ER mutants. The mutation G521R, which rendered the three mutants incapable of binding estradiol, also reduced, but did not abolish, their dominant negative activity. Immunoprecipitation with monoclonal or flag antibodies followed by Western blotting demonstrated that each of the original dominant negative ER mutants formed heterodimers with wild type ER. Rendering the dominant negative mutants dimerization deficient by the mutation L507R strongly reduced, but did not eliminate, their dominant negative activity. Deletion of the N-terminal A/B domain resulted in the nearly complete loss of inhibitory activity of the three dominant negative mutants. However, these double mutants retained their ability to heterodimerize with wild type ER, suggesting that dominant negative interference also occurs at an additional step beyond dimerization. Our data indicate that competition for ERE binding, formation of inactive heterodimers, and specific transcriptional silencing can all contribute to the dominant negative phenotype and that these receptors suppress the activity of wild type ER by acting at multiple steps in the ER-response pathway.

Animals↗

Follow-up after negative large loop excision of the transformation zone (LLETZ) of the cervix.

We performed a retrospective analysis of 204 patients who underwent large loop excision of the transformation zone (LLETZ) to determine whether women who have a negative LLETZ (no cervical intra-epithelial neoplasia (CIN) present) are at a lower risk of developing further abnormal cytology or CIN than women whose LLETZ is positive (CIN present). Overall 69 of the LLETZ samples were negative (34%) and 135 were positive (66%). The mean duration of negative cytology during follow up was 25.4 months (negative LLETZ) and 21.2 months (positive LLETZ) (P=0.03). In the negative LLETZ group, cytology did not miss any cases of persistent CIN at the 6-month follow-up visit and 39 repeat punch biopsies were all negative. There were 3/69 cases (4.3%) in the negative LLETZ group and 13/135 (9.6%) in the positive LLETZ group of persistent disease (CIN diagnosed at or as a result of the 6-month follow-up). Following a negative 6-month review, one woman developed an abnormal smear in the negative LLETZ group (1/66=1.5%) compared with 10 women (10/122=8.1%) in the positive LLETZ group. Recurrent CIN (CIN subsequently diagnosed following a negative 6-month review) was seen in 0/69 cases (0%) in the negative LLETZ group and 4/135 (3.2%) in the positive LLETZ group. We conclude that women who undergo a negative LLETZ may represent a low-risk group for developing further cytological and histological abnormalities.

Adult↗

Novel antipsychotics and negative symptoms.

Negative symptoms are a key feature of schizophrenia. Novel (atypical) antipsychotic drugs, unlike conventional antipsychotics, cause substantial reductions in Positive and Negative Symptom Scale (PANSS) scores. Negative symptoms, however, can arise from both the pathology of the disease (primary negative symptoms) and as side effects of antipsychotic drugs (secondary negative symptoms). Before the efficacy of a drug against negative symptoms can be determined, the physician must establish whether the positive results stem from reductions in primary negative symptoms or are merely due to improved extrapyramidal tolerability. Until recently, shortcomings in the design of clinical trials and the lack of distinction between primary and secondary symptoms made it impossible to answer this question. However, advances in clinical trial methodologies now make it possible to assess negative symptoms accurately, and a complex statistical approach, the path analysis, has been developed to differentiate between the direct and indirect effects of antipsychotic drugs on negative symptoms. With this approach, it has been shown that the efficacy of novel antipsychotics, such as sertindole, against negative symptoms is achieved largely through direct effects on primary negative symptoms. The requirements for an accurate assessment and differentiation of negative symptoms are outlined, and the importance of this for improving the treatment of schizophrenia is emphasized.

Antipsychotic Agents↗

Negative symptomatology in schizophrenic outpatients.

This study examines the prevalence of negative symptoms, and assesses the convergence of negative and depressive symptoms in 60 chronically ill schizophrenic outpatients. Negative symptoms were assessed with the Scale for the Assessment of Negative Symptoms and the negative symptom cluster of the Brief Psychiatric Rating Scale (BPRS). Depressive symptoms were assessed with the depression subscale of the Brief Symptom Inventory and the depressive symptom cluster of the BPRS. A majority of patients in this group of relatively stable, schizophrenic outpatients demonstrated mild to moderate degrees of both negative and depressive symptoms. Correlations were not significant between negative symptom and depressive symptom measures, which suggests that the symptom constructs are relatively independent. Comparisons between a subgroup with prominent negative symptoms (N = 18) and a subgroup with minimal negative symptoms (N = 32) also revealed no significant group differences in variables that characterize clinical course (i.e., age of onset and frequency and duration of hospitalization) or in the severity of depressive symptoms. This lack of any significant differences on the clinical course variables may be partially explained by the heterogeneity of negative symptoms. The constellation of negative symptoms may differ not only in etiology but also in their temporal relationships to other aspects of the patient's clinical course. Longitudinal studies will be needed to track the long-term outcome of negative and depressive symptoms.

Adolescent↗

New pharmacotherapeutic modalities for negative symptoms in psychosis.

Negative symptoms in schizophrenia comprise a psychopathologic and pathophysiologic syndrome which is absent from normal mental function. Renewed interest in negative symptoms has led to the development of better measuring instruments, among which is the Positive And Negative Syndrome Scale (PANSS), which provides a way of measuring and reporting positive and negative symptoms in a balanced and convenient form. A number of strategies are being investigated for treating negative symptoms. Dopamine agonists such as levodopa, amphetamines and bromocriptine have been shown to produce improvements in negative symptoms, although good, well-controlled clinical trials are lacking. Partial dopamine agonists, such as MAR 327, are also currently under investigation and results are expected soon. Tricyclic, selective serotonin reuptake inhibitors and monoamine oxidase antidepressants appear to be able to modify negative symptoms in schizophrenia, although, once again, carefully designed trials are needed. Modification of GABAergic transmission has shown little promise, but the use of glycine to augment transmission at N-methyl-D-aspartate (NMDA) synapses suggests that the strategy may be beneficial. These results also imply that altered glutamate receptor function may be partly responsible for negative symptoms. One strategy that has been shown to have a beneficial effect against negative symptoms is combined serotonin/dopamine antagonism. Clozapine was found to have this profile after its introduction, and the recently introduced antipsychotic, risperidone was developed intentionally to be a combined 5-HT2/D2 antagonist. Both risperidone and clozapine have been shown to be effective against negative symptoms. One problem associated with the assessment of drug effects on negative symptoms, however, is that drugs can act on both primary and secondary negative symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Affective Symptoms↗

Synthesis of vesicular stomatitis virus negative-strand RNA in vitro: dependence on viral protein synthesis.

An in vitro system is described which supports the synthesis of vesicular stomatitis virus (VSV) negative-strand RNA. The major components of this system are (i) an mRNA-dependent rabbit reticulocyte lysate to carry out cell-free protein synthesis, (ii) the five VSV mRNAs to program VSV-specific protein synthesis, and (iii) nucleocapsids containing positive- and negative-strand genome-length RNA. The protein products synthesized in the system in response to addition of saturating amounts of the five VSV mRNA's included polypeptides which comigrated in acrylamide gels with the five VSV proteins. Approximately 200 pmol of protein per ml was synthesized during a 90-min reaction. The RNA products synthesized in the system included all five of the VSV mRNA's and, in addition, negative-strand, genome-sense RNA. All of the negative-strand RNA, which represented 2 to 5% of the total RNA product synthesized in vitro, banded in CsCl at the position of nucleocapsids. All of the mature mRNA's made in the system pelleted in CsCl. This technique allowed a clear separation of negative-strand product from the mRNA products and facilitated further analysis of the negative-strand product. The amount of negative-strand product produced in the system was shown to be a function of the amount of concurrent protein synthesis in the system. An increase in the level of protein synthesis led to an increase in the amount of negative-strand RNA synthesized, whereas inhibition of protein synthesis by cycloheximide resulted in a 70% inhibition of negative-strand synthesis. In contrast to the negative-strand RNA product, the amount of transcriptive product was decreased by 50% in the presence of maximum levels of viral protein synthesis. This inhibition was reversed by adding cycloheximide. Characterization of the negative-strand product by Northern blot analysis demonstrated that negative-strand product was being synthesized which hybridized to all five of the VSV mRNA's and, hence, that product representing all of the VSV cistrons was being made. This in vitro system offers an opportunity to study factors involved in the promotion of VSV genome replication as well as those responsible for the regulation of transcription.

Cell-Free System↗

Cervical cancers diagnosed after negative results on cervical cytology: perspective in the 1980s.

OBJECTIVES: To assess the magnitude of the problem of interval cancers of the cervix (those that are diagnosed within a short time after negative screening test results) in the 1980s, to compare the nature of interval cancers in younger women with that in older women, and, by reviewing negative cervical smears, to determine the proportion of interval cancers that might represent the development of malignancy anew compared with the proportion that might be associated with difficulties in sampling or errors in reporting. DESIGN: An audit of the interval cases of cervical cancer that had been diagnosed within 36 months of a smear having been reported as negative by the Victorian Cytology Gynaecological Service among women registered with cervical cancer during 1982-6. SETTING: The Victorian Cytology Gynaecological Service, a free public sector cytology laboratory in Victoria, Australia. SUBJECTS: 138 Women, all of whom had had cervical cancer diagnosed during the 36 months after having had a negative cervical smear. Subjects were divided into two age groups: younger women, aged less than 35; older women, aged 35-69. INTERVENTIONS: Negative slides were reviewed for evidence of optimal sampling and for the presence of cellular abnormalities that had been missed at the time of the original reporting. MAIN OUTCOME MEASURES: The number of interval cases of cancer of the cervix registered during 1982-6. The proportion of interval cases occurring in younger women and the proportion occurring in older women. Division of women into three risk categories based on clinical history and screening history that broadly corresponded to the probability that a diagnosis of cervical cancer might be expected during the 36 months after the issuing of a negative smear report. RESULTS: 138 Of 1044 (13.2%) women who had been registered with cervical cancer during 1982-6 had had one or more negative smears during the 36 months preceding the diagnosis of cancer. Interval cancers comprised a larger proportion of registrations of cervical cancer in women aged less than 35 years than in women aged 35-69 (21.1% v 11.0%, p less than 0.01). Women with interval cancer who had had at least three negative smears during the 10 years before the diagnosis of cancer were commoner in the younger age group than in the older age group (7.0% v 2.5%, p less than 0.01). When, however, the number of observed cases of squamous cell carcinoma was related to the number of expected cases in the absence of screening, no significant difference was found between the two age groups (6.8% v 4.8%, p greater than 0.10). The rate of diagnosis of interval cancer per 100,000 negative tests was lower among younger women than among older women (10/100,000 v 16/100,000). Review of the negative slides showed that 11.9% were again considered to be negative with an optimal sample having been obtained as evidenced by the presence of endocervical cells or metaplastic cells, or both. CONCLUSIONS: Interval cancers might comprise a larger proportion of all registered cases of cervical cancer among younger women owing to the larger proportion of such cancers being prevented in this age group. Among women with interval cancer review of the negative slides showed that most were accounted for by suboptimal sampling or by errors of reporting.

Adult↗

Use of general-purpose negation detection to augment concept indexing of medical documents: a quantitative study using the UMLS.

OBJECTIVES: To test the hypothesis that most instances of negated concepts in dictated medical documents can be detected by a strategy that relies on tools developed for the parsing of formal (computer) languages-specifically, a lexical scanner ("lexer") that uses regular expressions to generate a finite state machine, and a parser that relies on a restricted subset of context-free grammars, known as LALR(1) grammars. METHODS: A diverse training set of 40 medical documents from a variety of specialties was manually inspected and used to develop a program (Negfinder) that contained rules to recognize a large set of negated patterns occurring in the text. Negfinder's lexer and parser were developed using tools normally used to generate programming language compilers. The input to Negfinder consisted of medical narrative that was preprocessed to recognize UMLS concepts: the text of a recognized concept had been replaced with a coded representation that included its UMLS concept ID. The program generated an index with one entry per instance of a concept in the document, where the presence or absence of negation of that concept was recorded. This information was used to mark up the text of each document by color-coding it to make it easier to inspect. The parser was then evaluated in two ways: 1) a test set of 60 documents (30 discharge summaries, 30 surgical notes) marked-up by Negfinder was inspected visually to quantify false-positive and false-negative results; and 2) a different test set of 10 documents was independently examined for negatives by a human observer and by Negfinder, and the results were compared. RESULTS: In the first evaluation using marked-up documents, 8,358 instances of UMLS concepts were detected in the 60 documents, of which 544 were negations detected by the program and verified by human observation (true-positive results, or TPs). Thirteen instances were wrongly flagged as negated (false-positive results, or FPs), and the program missed 27 instances of negation (false-negative results, or FNs), yielding a sensitivity of 95.3 percent and a specificity of 97.7 percent. In the second evaluation using independent negation detection, 1,869 concepts were detected in 10 documents, with 135 TPs, 12 FPs, and 6 FNs, yielding a sensitivity of 95.7 percent and a specificity of 91.8 percent. One of the words "no," "denies/denied," "not," or "without" was present in 92.5 percent of all negations. CONCLUSIONS: Negation of most concepts in medical narrative can be reliably detected by a simple strategy. The reliability of detection depends on several factors, the most important being the accuracy of concept matching.

Abstracting and Indexing↗

Differential efficacy of olanzapine for deficit and nondeficit negative symptoms in schizophrenia.

OBJECTIVE: Atypical antipsychotic medications have generally been found to be more effective than conventional antipsychotics in the treatment of negative symptoms. Whether the benefits derived from the atypical agents are the result of improvements in primary versus secondary negative symptoms is unclear. The authors examined the effects of olanzapine on primary and secondary negative symptoms for patients with severe negative symptoms who did or did not have the deficit syndrome. METHOD: Thirty-nine outpatients with schizophrenia and severe negative symptoms were assessed for the presence of the deficit syndrome and entered into a 12-week, open-label study of olanzapine. Positive and negative symptoms, extrapyramidal side effects, quality of life, and level of functioning of the patients were assessed at baseline and endpoint. RESULTS: All 39 patients completed the 12-week protocol; 13 of the patients had deficit negative symptoms, and 26 had nondeficit negative symptoms. Patients who had nondeficit negative symptoms demonstrated improvements in positive and negative symptoms, level of functioning, and extrapyramidal side effects over baseline. In contrast, patients meeting criteria for the deficit syndrome improved significantly over baseline only in extrapyramidal side effects. CONCLUSIONS: The results of this study suggest that olanzapine is efficacious for secondary negative symptoms in schizophrenia but fail to support the contention that olanzapine has a direct beneficial effect on primary negative symptoms.

Adult↗

Increasing negative lymph node count is independently associated with improved long-term survival in stage IIIB and IIIC colon cancer.

PURPOSE: The purpose of this study was to examine the impact of the number of negative lymph nodes on survival in patients with stage III colon cancer. PATIENTS AND METHODS: Patients who underwent surgery for stage III colon cancer between January 1988 and December 1997 were identified from the Surveillance, Epidemiology and End Results cancer registry. The number of negative and positive nodes was determined for 20,702 eligible patients. Disease-specific survival was examined by substage according to the number of negative nodes identified. A proportional hazards model was constructed to determine the effect of the number of negative nodes on survival. RESULTS: For stage IIIB and IIIC patients, there was a significant decrease in disease-specific mortality as the number of negative nodes increased; cumulative 5-year cancer mortality was 27% in stage IIIB patients with 13 or more negative nodes identified versus 45% in those with three or fewer negative lymph nodes evaluated (P < .0001). In patients with stage IIIC cancer, those with 13 or more negative nodes had a 5-year mortality of 42% versus 65% in those with three or fewer negative lymph nodes evaluated (P < .0001). There was no association between the number of negative nodes identified and disease-specific survival for patients with stage IIIA disease. After controlling for the number of positive nodes, a higher number of negative nodes was found to be independently associated with improved disease-specific survival. CONCLUSION: The number of negative nodes is an important independent prognostic factor for patients with stage IIIB and IIIC colon cancer.

Aged↗