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Evaluation of severity scoring systems in ICUs--translation, conversion and definition ambiguities as a source of inter-observer variability in Apache II, SAPS and OSF.

OBJECTIVE: To explore translation, conversion and definition ambiguities, when using severity scoring systems in patients admitted to intensive care units (ICUs). DESIGN: A prospective study of the prognosis of acute renal failure in ICUs. SETTING: The study was conducted in 20 French ICUs. PATIENTS: 360 patients presenting with severe acute renal failure were studied during their ICU stay. MEASUREMENTS AND RESULTS: The inter-observer variability of Apache II (acute physiology and chronic health evaluation), SAPS (simplified acute physiology score), and OSF (organ-system failure) was considered. For Apache II, we explored the uncertainty of measurements arising from conversion into SI units, the rounding procedures used for the non-inclusive intervals defined for quantitative parameters such as age, mean arterial pressure (MAP) or serum creatinine, the absence of definition of acute renal failure (ARF) and its consequence on doubling serum creatinine values, and the absence of guidelines in the case of spontaneous ventilation when arterial blood gases (ABG) and forced inspiratory oxygen (FIO2) were not measured. The resulting variability was evaluated, calculating the lowest and the highest value of the scoring system for each patient. The mean difference by patient was greater than 1.5 (p < 0.0001). Other examples were presented and discussed for SAPS and OSF. CONCLUSIONS: Translation, conversion and definition ambiguities are a source of inter-observer variability and increase the risk of classification and/or selection biases. This gives rise to particular concern in the design and analysis of multicenter trials of meta-analysis, and improvement of these scoring systems should be envisaged in the future.

APACHE↗

A comparison of two measures of low response to alcohol among heavy drinking male college students: implications for indicated prevention.

Low response (LR) to alcohol is a risk factor that strongly predicts later problems. This study compares subjective measures of high tolerance (HT) to measures of LR, using the Self-Rating of Effects of Alcohol (SRE) form. First-year heavy drinking students (N = 250) at an all-male college completed a survey during a mandatory class that included the SRE, past month peak consumption, 2-week heavy episodic use, family history, self-reported high tolerance, and whether it takes more alcohol to become impaired compared to others. The SRE identified LR for 96.7% of those reporting HT and 100% of those reporting both HT and that it takes comparatively more alcohol to become impaired. The measure of HT correlated more with heavy drinking than did that of LR (peak of 14.5 drinks and 4.3 occasions of heavy episodic drinking vs. 12.6 and 3.7) whereas those identified as not LR drank less than those who reported no HT (peak of 6.1 drinks and 1.3 occasions of heavy episodic drinking vs. 9.6 and 2.4). Those reporting uncertainty about HT averaged peaks of 10 drinks and 3.13 occasions of heavy episodic drinking; 73.6% scored LR on the SRE. These data suggest that, at least in a heavy drinking group, the SRE may be most effective as a selected follow-up to an initial two-question screening. Self-reporting a high tolerance provides as much information as the 12-question SRE and is associated with heavier use. The SRE may provide corrective feedback to those who report uncertainty about HT or who give conflicting responses to the two screening questions.

Adolescent↗

Effects of uncertainty on melodic information processing.

In three experiments, musically trained and untrained adults listened to three repetitions of a 5-note melodic sequence followed by a final melody with either the same tune as those preceding it or differing in one position by one semitone. In Experiment 1, ability to recognize the final sequence was examined as a function of redundancy at the levels of musical structure in a sequence, contour complexity of transpositions in a trial, and trial context in a session. Within a sequence, tones were related as the major or augmented triad; within a trial, the four sequences began on successively higher notes (simple macrocontour) or on randomly selected notes (complex macrocontour); and within a session, trials were either blocked (all major or all augmented) or mixed (major and augmented randomly selected). Performance was superior for major melodies, for systematic transpositions within a trial (simple macrocontours), for blocked trials, and for musically trained listeners. In Experiment 2, we examined further the effect of macrocontour. Performance on simple macrocontours exceeded that on complex, and excluded the possibility that repetition of the 20-note sequences provided the entire benefit of systematic transposition in Experiment 1. The effect of musical structure (major/augmented) was also replicated. In Experiment 3, listeners provided structure ratings of ascending 20-note sequences from Experiment 2. Ratings on same trials were higher than those on corresponding different trials, in contrast to performance scores for augmented same and different trials in previous experiments. The concept of functional uncertainty was proposed to account for recognition difficulties on augmented same trials. The significant effects of redundancy on all the levels examined confirm the utility of the information-processing framework for the study of melodic sequence perception.

Adolescent↗

A critical review of guidelines for low back pain treatment.

MAIN PROBLEM: Little is known about the methodological quality of guidelines for low back pain treatment. We evaluated the methods used by the developers according to established standards. METHODS: PubMed, guideline databases, and the World Wide Web were used to identify guidelines. Seventeen guidelines met the inclusion criteria: interventions for low back pain stated, recommendations based on or explicitly linked to evidence, and English version available. Guidelines were evaluated independently by two appraisers using a practical tool for this purpose, Users' Guides to the Medical Literature, and the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument. RESULTS: Thirteen guidelines (76%) specified the most important therapies applied, but only nine (53%) included a complete description of the target population. Explicit processes to identify, select, and combine evidence were described in only six guidelines (35%). Few guidelines (3; 18%) explicitly considered all main outcomes when formulating therapeutic recommendations, and none contained a process to determine the relative value of different outcomes. Methodological criteria for grading the strength of the recommendations varied, and were often insufficiently specified. None of the guidelines assessed the impact of uncertainty associated with the evidence and values used. According to AGREE the quality score was highest for the scope and purpose, and clarity and presentation domains, and lowest for editorial independence and applicability. With regard to the recommendations, there was consensus for some of the interventions for acute pain (analgesics and NSAIDs, maintaining physical activity, and avoiding excessive bed rest), but explicit recommendations were lacking or ambiguous for 41% of the interventions. Most of the guidelines did not contemplate specific recommendations for chronic pain. CONCLUSIONS: A small number of the available guidelines for low back pain treatment achieved acceptable results for specific quality criteria. In general, the methods to develop the guidelines' therapeutic recommendations need to be more rigorous, more explicit and better explained. In addition, greater importance should be placed on the recommendations for chronic pain.

Activities of Daily Living↗

The launch of MCBEND 10.

MCBEND 10 is the latest release of the general radiation transport Monte Carlo code from the ANSWERS Software Service of Serco Assurance. MCBEND is developed within a Nuclear Code Development (NCD) partnership between Serco Assurance and BNFL. The ANSWERS vision is 'to provide easy-to-use software that meets the current and emerging needs of the user community'. In the case of MCBEND, this vision focuses on the key areas of accuracy, understanding of uncertainties, efficiency and user-friendliness. MCBEND 10 is a major launch of the code with many new and enhanced features. New developments in MCBEND 10 include automatic splitting mesh generation, point energy adjoint for neutrons, calculation of uncertainty in the results due to material cross section uncertainties and a unified source facility. Enhanced features include improved temperature treatment, extended scoring of sensitivity to geometry perturbations, geometry improvements, extensions to formulae and improved user guide image. The user-friendliness of the MCBEND code has been further enhanced by recent developments to the visualisation tools, VISAGE and VISTA-RAY. Developments have been made to the three-dimensional visualisation tool, VISTA-RAY, to simplify the detailed checking of a model, with the option to use a mouse-pointer to select regions of interest for further detail and to visually highlight incorrectly defined areas. A further development to VISTA-RAY is the inclusion of the capability to overlay a representation of a user-designated set of results from a MCBEND analysis on the model. Improvements have also been made to the graphical user interface LaunchPad for submitting and controlling calculation submission, with a common user-image across all the systems. Recent enhancements to LaunchPad include a job-scheduler to simplify processing multiple tasks. A selection of the new developments in MCBEND 10, VISTA-RAY and LaunchPad will be described in this paper.

Algorithms↗

scRNA-seq and bulk RNA-seq reveal the characteristics of macrophage copper metabolism and establish a risk signature in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent malignancy with an urgent need for improved prognostic stratification and treatment-response prediction. This study aimed to explore a macrophage copper metabolism-associated prognostic model and to investigate the relationship between this risk model and the tumor immune microenvironment. METHODS: The FindClusters function was used to analyze cell clusters, and CellChat and CellPhoneDB/LIANA were employed for cell-cell communication analysis. Copper metabolism-related genes were sourced from the MSigDB database. A prognostic risk model was established using least absolute shrinkage and selection operator (LASSO) analysis and multivariate Cox regression analysis, and a nomogram was constructed by integrating the prognostic model with clinicopathological factors. Additional analyses were performed to map the seven model genes in single-cell data, assess model uncertainty and robustness, evaluate macrophage/copper/cuproptosis-related transcriptional programs, and examine the correlations between risk score, immune infiltration and predicted drug sensitivity. RESULTS: Using single-cell RNA sequencing (scRNA-seq) data, we identified four macrophage subpopulations. Macrophages with high SPP1 expression showed close interaction with T cell populations and were associated with copper ion metabolism. By incorporating 141 copper metabolism-related genes and using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort, we constructed a seven-gene risk prediction model. Additional single-cell mapping showed that the model genes were detectable in the HCC single-cell dataset and showed a macrophage-associated expression pattern. The model showed moderate prognostic discrimination in TCGA-LIHC, whereas its external performance was heterogeneous and remained evaluable across external cohorts, with performance varying among datasets. Immune and mechanism-related analyses suggested that the risk signature was associated with macrophage-related infiltration, copper metabolism and cuproptosis-related transcriptional programs. Drug sensitivity analysis nominated Daporinad as a computationally predicted candidate compound, supporting Daporinad as a pharmacogenomic candidate for follow-up investigation. CONCLUSIONS: By integrating scRNA-seq and bulk RNA sequencing (RNA-seq) data, we constructed a macrophage copper metabolism-associated prognostic signature for HCC. The risk score was associated with survival, immune microenvironment features and predicted drug response, providing a transcriptomic framework for risk stratification and therapeutic hypothesis generation.

Hepatocellular carcinoma (HCC)↗

Population-scale detection of methylation outliers from long-read genome sequencing.

BACKGROUND: Aberrant DNA methylation can mediate the functional effects of rare genetic variation and contribute to imprinting disorders, repeat expansion diseases, and other pathogenic regulatory mechanisms. Long-read sequencing technologies now enable genome-wide detection of CpG methylation alongside genetic variation from a single assay. However, methods for systematic identification and interpretation of methylation outliers from long-read sequencing data remain limited. METHODS: We developed METAFORA, a computational workflow for detecting methylation outlier regions from PacBio and Oxford Nanopore long-read sequencing data. METAFORA constructs population-level methylation references, segments the genome into correlated CpG blocks, infers technical and biological sources of variation through hidden factor estimation, models uncertainty due to variable depth sequencing, and computes covariate-adjusted methylation outlier scores for individual samples. We applied METAFORA across large long-read sequencing cohorts and integrated methylation outliers with multi-omic data. METAFORA is implemented as a snakemake workflow available at https://github.com/tjense25/METAFORA. RESULTS: METAFORA identified methylation outlier regions associated with rare structural variants, tandem repeat expansions, and imprinting abnormalities. We found outlier regions were enriched for molecular outliers across transcriptomic and chromatin accessibility datasets, supporting their functional relevance in gene regulation. In a representative case, METAFORA identified an imprinting defect affecting the GNAS locus associated with an STX16 deletion. CONCLUSIONS: METAFORA enables scalable detection and interpretation of methylation outliers from long-read sequencing data and provides a framework for integrating epigenetic outliers with genomic and multi-omic analyses. These approaches may improve interpretation of rare regulatory variation and support discovery of clinically relevant epigenetic abnormalities in genomic medicine.

DNA methylation↗

Beliefs in obsessive-compulsive disorder.

Several types of beliefs have been hypothesized to be associated with obsessive-compulsive disorder (OCD), including responsibility for harm, need to control thoughts, overestimates of threat, intolerance of uncertainty, and beliefs about the consequences of anxiety and capacity to cope. The present study compared 62 subjects with OCD, 45 with other anxiety disorders (AD) and 34 controls, using 3 measures of OCD-related beliefs. OCD subjects scored higher than AD and control samples on 2 general belief measures. A closer analysis of specific belief domains indicated that OCD subjects scored higher than AD and control subjects on all 6 specific belief domains (responsibility, control, estimation of threat, tolerance of uncertainty, beliefs about the consequences of anxiety, and the capacity to cope). Four of the 6 domains showed reasonable convergent and discriminant validity with measures of OCD symptoms compared to other psychopathology; anxiety and coping beliefs were the exceptions. In regression analyses, cognitive measures contributed significant explanatory power beyond mood state and worry with uncertainty predicting severity of OCD symptoms above all other belief domains. Further research on OCD-relevant belief domains in etiology, maintenance and treatment is warranted.

Adaptation, Psychological↗

Further results on the reliability of the Parental Bonding Instrument (PBI) in an Italian sample of schizophrenic patients and their parents.

The reliability of the Italian version of the Parental Bonding Instrument (PBI) was assessed in a group of 26 schizophrenic patients and their parents. In both groups, internal consistency indices were satisfactory and mean PBI scores at test and retest were stable. The test-retest reliability coefficients for the PBI scales of parents ranged from .65 to .67, those of the patients from .32 (paternal-protection score) to .67 (maternal-care score). The less satisfactory test-retest reliability of patients' paternal protection score was due to minor intra-category rather than inter-category variations in their ratings. This suggests difficulties with a four-point rating scale, which might depend partly on the generally poor schooling of the sample, but it may also reflect uncertainty of schizophrenic patients concerning fathers' controlling behavior. Further studies should pay attention to this factor. Patients' PBI mean scores are compatible with an affection-less control rearing style, while those of their parents, characterized by similar poor care but less control, are consistent with a pattern of weak parental bonding.

Adolescent↗

[Rational choice, prediction, and medical decision. Contribution of severity scores].

The aim of this study was to determine what type of representation the medical doctor adopted concerning the uncertainty about the future in critically ill patients in the context of preoperative evaluation and intensive care medicine and to explore through the representation of the patient health status the different possibilities of choice he was able to make. The role played by the severity classification systems in the process of medical decision-making under probabilistic uncertainty was assessed according to the theories of rational behaviour. In this context, a medical rationality needed to be discovered, going beyond the instrumental status of the objective and/or subjective constructions of rational choice theories and reaching a dimension where means and expected ends could be included.

Critical Care↗

[Development of physical and sports activity in patients before and after implantation of a total knee endoprosthesis. A prospective study of 40 patients].

AIM: The aim of this prospective study was to analyse the development of activities of daily living (ADL) as well as sports activities in patients suffering from osteoarthritis of the knee and undergoing total knee replacement. 40 patients with 42 operated knee joints were included in this study. METHOD: 38 patients (40 knee replacements) recieved a PFC endoprosthesis, 2 patients recieved a GSB endoprosthesis. In 28 cases (71%) we found generalized degenerative joint changes, in 7 cases (17%) a varus deformity and in 2 cases (5%) a valgus deformity. Post-traumatic osteoarthritis was seen in 3 cases (7%). We used the PFC endoprosthesis in patients with stable ligaments, in unstable joints we used the GSB endoprosthesis. Patients were reviewed clinically and radiographically and answered a questionnaire with special reference to ADL (walking, gymnastics, bicycling, homework, swimming, gardening). For evaluation of the results we used the Ranawat & Shine score. Pain was determined with the VAS (visual analogue pain scale). RESULTS: The activity level increased from preoperatively 62.5% up to 91.5% 2 years postoperatively. This was mainly due to walking and gymnastics. Overall sports activities decreased. There was a high uncertainty regarding activities due to patients' lack of knowledge about possible postoperative load capacity of the new joint. The average score according to Ranawat & Shine increased from preoperative 56.98 to 75.89 points out of 100. Most significantly we found an improvement in the pain rating. There was an improvement of 73% under resting and of 81% under activity conditions. CONCLUSION: With this prospective study we can demonstrate the benefit for patients undergoing knee replacement surgery with respect to activities of daily living and especially pain reduction.

Activities of Daily Living↗

GOtcha: a new method for prediction of protein function assessed by the annotation of seven genomes.

BACKGROUND: The function of a novel gene product is typically predicted by transitive assignment of annotation from similar sequences. We describe a novel method, GOtcha, for predicting gene product function by annotation with Gene Ontology (GO) terms. GOtcha predicts GO term associations with term-specific probability (P-score) measures of confidence. Term-specific probabilities are a novel feature of GOtcha and allow the identification of conflicts or uncertainty in annotation. RESULTS: The GOtcha method was applied to the recently sequenced genome for Plasmodium falciparum and six other genomes. GOtcha was compared quantitatively for retrieval of assigned GO terms against direct transitive assignment from the highest scoring annotated BLAST search hit (TOPBLAST). GOtcha exploits information deep into the 'twilight zone' of similarity search matches, making use of much information that is otherwise discarded by more simplistic approaches. At a P-score cutoff of 50%, GOtcha provided 60% better recovery of annotation terms and 20% higher selectivity than annotation with TOPBLAST at an E-value cutoff of 10(-4). CONCLUSIONS: The GOtcha method is a useful tool for genome annotators. It has identified both errors and omissions in the original Plasmodium falciparum annotation and is being adopted by many other genome sequencing projects.

Animals↗

The uncertainty principle and industry-sponsored research.

BACKGROUND: Reporting of pharmaceutical-industry-sponsored randomised clinical trials often result in biased findings, either due to selective reporting of studies with non-equivalent arms or publication of low-quality papers, wherein unfavourable results are incompletely described. A randomised trial should be conducted only if there is substantial uncertainty about the relative value of one treatment versus another. Studies in which intervention and control are thought to be non-equivalent violates the uncertainty principle. METHODS: We examined the quality of 136 published randomised trials that focused on one disease category (multiple myeloma) and adherence to the uncertainty principle. To evaluate whether the uncertainty principle was upheld, we compared the number of studies favouring experimental treatments over standard ones. We analysed data according to the source of funding. FINDINGS: Trials funded solely or in part by 35 profit-making organisations had a trend toward higher quality scores (mean 2.94 [SD 1.3]; median 3) than randomised trials supported by 95 governmental or other non-profit organisations (2.4 [0.8]; 2; p=0.06). Overall, the uncertainty principle was upheld, with 44% of randomised trials favouring standard treatments and 56% innovative treatments (p=0.17); mean and median preference evaluation scores were 3.7 (1.0) and 4. However, when the analysis was done according to the source of funding, studies funded by non-profit organisations maintained equipoise favouring new therapies over standard ones (47% vs 53%; p=0.608) to a greater extent than randomised trials supported solely or in part by profit-making organisations (74% vs 26%; p=0.004). INTERPRETATION: The reported bias in research sponsored by the pharmaceutical industry may be a consequence of violations of the uncertainty principle. Sponsors of clinical trials should be encouraged to report all results and to choose appropriate comparative controls.

Bias↗

Methodological issues when comparing hearing thresholds of a group with population standards: the case of the ferry engineers.

OBJECTIVES: To discuss appropriate and inappropriate methods for comparing distributions of hearing thresholds of a study group with distributions in population standards and to determine whether the thresholds of Washington State Ferries engineers are different from those of men in the general population, using both frequency-by-frequency comparisons and analysis of audiometric shape. DESIGN: The most recent hearing conservation program audiograms of 321 noise-exposed engineers, ages 35 to 64, were compared with the predictions of Annexes A, B, and C from ANSI S3.44. There was no screening by history or otoscopy; all audiograms were included. 95% confidence intervals (95% CIs) were calculated for the engineers' median thresholds for each ear, for the better ear (defined two ways), and for the binaural average. For Annex B, where 95% CIs are also available, it was possible to calculate z scores for the differences between Annex B and the engineers' better ears. Bulge depth, an audiometric shape statistic, measured curvature between 1 and 6 kHz. RESULTS: Engineers' better-ear median thresholds were worse than those in Annex A but (except at 1 kHz) were as good as or better than those in Annexes B and C, which are more appropriate for comparison to an unscreened noise-exposed group like the engineers. Average bulge depth for the engineers was similar to that of the Annex B standard (no added occupational noise) and was much less than that of audiograms created by using the standard with added occupational noise between 90 and 100 dBA. CONCLUSIONS: Audiograms from groups that have been selected for a particular exposure, but, without regard to severity, can appropriately be compared with population standards, if certain pitfalls are avoided. For unscreened study groups with large age-sex subgroups, a simple method to assess statistical significance, taking into consideration uncertainties in both the study group and the comparison standard, is the calculation of z scores for the proportion of better-ear thresholds above the Annex B median. A less powerful method combines small age-sex subgroups after age correction. Small threshold differences, even if statistically significant, may not be due to genuine differences in hearing sensitivity between study group and standard. Audiometric shape analysis offers an independent dimension of comparison between the study group and audiograms predicted from the ANSI S3.44 standard, with and without occupational noise exposure. Important pitfalls in comparison to population standards include nonrandom selection of study groups, inappropriate choice of population standard, use of the right and left ear thresholds instead of the better-ear threshold for comparison to Annex B, and comparing means with medians. The thresholds of the engineers in this study were similar to published standards for an unscreened population.

Adult↗

Using complexity for the estimation of Bayesian networks.

Statistical inference of graphical models has become an important tool in the reconstruction of biological networks of the type which model, for example, gene regulatory interactions. In particular, the construction of a score-based Bayesian posterior density over the space of models provides an intuitive and computationally feasible method of assessing model uncertainty and of assigning statistical confidence to structural features. One problem which frequently occurs with this approach is the tendency to overestimate the degree of model complexity. Spurious graphical features obtained in this way may affect the inference in unpredictable ways, even when using scoring techniques, such as the Bayesian Information Criterion (BIC), that are specifically designed to compensate for overfitting. In this article we propose a simple adjustment to a BIC-based scoring procedure. The method proceeds in two steps. In the first step we derive an independent estimate of the parametric complexity of the model. In the second we modify the BIC score so that the mean parametric complexity of the posterior density is equal to the estimated value. The method is applied to a set of test networks, and to a collection of genes from the yeast genome known to possess regulatory relationships. A Bayesian network model with binary responses is employed. In the examples considered, we find that the number of spurious graph edges inferred is reduced, while the effect on the identification of true edges is minimal.

Algorithms↗

Substitute decision-making: measuring individually mediated sources of uncertainty.

One aspect of O'Connor's Decisional Conflict Scale [O'Connor, A.M., Validation of a decisional conflict scale, Med. Decis. Making 15 (1995) 25-30] is the assessment of selected factors (perceived lack of information, undue social pressure, lack of support from others, and lack of clarity about personal values) that are believed to contribute to decisional uncertainty. This study explored the appropriateness of this uncertainty measure in the substitute decision-making context. Forty-nine mothers deciding on gastrostomy tube insertion for their children completed the scale, and also provided verbal reports about the contributory factors. For each of the four factors, relatively high-, moderate-, and low-scoring sub-groups were identified; then the associated verbal reports were examined for across-sub-group differences. Differences in verbal reports about information (chi 2 = 6.990, P = 0.0082), perceived pressure (chi 2 = 8.377, P = 0.0038), social support (chi 2 = 5.573, P = 0.0182), and perceived gains and losses (chi 2 = 3.85, P = 0.0499; chi 2 = 5.76, P = 0.0164) were observed, implying consistency between quantitative scores and verbal reports. This quantitative/qualitative hybrid approach may be clinically useful for assessing individually mediated factors contributing to decision uncertainty, and for evaluating therapeutic interventions in other substitute decision-making contexts.

Adolescent↗

Laparoscopic treatment of blunt splenic injuries: initial experience with 11 patients.

BACKGROUND: Nonoperative treatment of splenic injuries is the current standard of care for hemodynamically stable patients. However, uncertainty exists about its efficacy for patients with major polytrauma, a high Injury Severity Score (ISS), a high grade of splenic injury, a low Glasgow Coma Score (GCS), and important hemoperitoneum. In these cases, the videolaparoscopic approach could allow full abdominal cavity investigation, hemoperitoneum evacuation with autotransfusion, and spleen removal or repair. METHODS: This study investigated 11 hemodynamically stable patients with severe polytrauma who underwent emergency laparoscopy. The mean ISS was 29.0 +/- 3.9, and the mean GCS was 12.1 +/- 1.6. A laparoscopic splenectomy was performed for six patients, whereas splenic hemostasis was achieved for five patients, involving one electrocoagulation, one polar resection, and three polyglycolic mesh wrappings. RESULTS: The average length of the operation was 121.4 +/- 41.6 min. There were two complications (18.2%), with one conversion to open surgery (9.1%), and no mortality. CONCLUSIONS: Laparoscopy is a safe, feasible, and effective procedure for evaluation and treatment of hemodynamically stable patients with splenic injuries for whom nonoperative treatment is controversial.

Adolescent↗

Diagnostic discrimination and cost effective assay strategy for leukocyte alkaline phosphatase.

Decreased leukocyte alkaline phosphatase (LAP) is a first line test for chronic myelogenous leukemia (CML), generally preceding a diagnostic algorithm which also includes bone marrow biopsy, cytogenetic analysis, and molecular diagnostics. We found the analytical uncertainty of LAP assays to range from over 100% coefficient of variation at low scores to about 20% at high scores. However, the receiver-operator characteristics derived from LAP determinations in 50 consecutive cases suggest that a suitably high diagnostic decision threshold still can eliminate false negatives. As a consequence of such a strategy, as many as half the tested patients, classified unequivocally as the negatives, can avoid further invasive and costly workup. On the other hand, serial LAP determinations, whether performed to detect change to a lower or to a higher score, are unlikely to produce conclusive diagnostic signals exceeding analytical 'noise.'

Alkaline Phosphatase↗