PATHOLOGY OF LONG-CHAIN 3-HYDROXYACYL-COA DEHYDROGENASE DEFICIENCY CAUSED BY THE G1528C MUTATION

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is a recently discovered disorder affecting the mitochondrial-oxidation of fatty acids. There have been few reports of the pathologic findings in-oxidation defects. We examined pathologic specimens from 16 patients with this disorder (11 patients were homozygous for the common mutation G1528C, 5 patients were siblings with a similar clinical presentation). Autopsies were performed on all 15 patients who died, and liver biopsy specimens were available from 8 patients. Hepatomegaly and steatosis of the liver, found in every patient, were often combined with fibrosis or cirrhosis. Cardiomegaly and accumulation of fat in the myocardium, renal tubules, and skeletal muscle were found in many patients. A detailed neuropathologic examination was performed on six patients, and brain specimens obtained at autopsy were examined in four others. In general, neuropathologic findings were mild and unspecific, but vacuolization was detected in the deep gray matter and in the cerebellum and brain stem nuclei of five patients. In one patient the vacuolization was prominent; in the other four it was milder and more focal. The vacuoles seemed to be either in the neuropil or associated with swollen hydropic cells. The uniform pattern of histopathologic changes facilitates the diagnostics in this severe disorder, allowing opportunities for therapy and prenatal diagnosis.     

Visual impairment and refractive errors in school children in Andhra Pradesh,India

Purpose:Addressing childhood vision impairment (VI) is one of the main goals of the World Health Organization’s (WHO) combating blindness strategies. The primary aim of this study was to estimate the prevalence of VI, causes, and its risk factors in school children in Krishna district, Andhra Pradesh, India.Methods:Children aged 4–15 years were screened in schools using the 6/12 Snellen optotype by trained community eye health workers, and those who failed the test and those reported or found to have obvious eye conditions were referred to primary (VC), secondary (SC), or tertiary (TC) care centre appropriately, where they underwent a complete eye examination including cycloplegic refraction and fundus examination.Results:A total of 56,988 children were screened, of whom 51.18% were boys. The mean age was 9.69 ± 3.26 years (4–15 years). Overall, 2,802/56,988 (4.92%) children were referred to a VC, of which 632/56,988 (1.11%) required referral to SC/TC. PVA of <6/12 was found in 1.72% (95% confidence interval [CI]: 1.61–1.83). The prevalence of refractive error (corrected and uncorrected) was 2.38% (95% CI: 2.26–2.51) and myopia was 2.17% (95% CI: 2.05–2.29). In multivariable analysis, older children, those in urban schools, private schools, and children with a disability had an increased risk of VI and myopia. Additionally, the risk of myopia was higher among girls than boys. Of those referred and reached SC/TC, 73.64% were due to avoidable causes.Conclusion:Childhood VI prevalence was 1.72% in this region. Uncorrected refractive error (URE) was the major cause of VI in children. Older age, schools in urban locations, private schools, and the presence of disability were associated with the risk of VI among children.     

《医林改错》方药临床运用

清代医学家王清任之《医林改错》,阐发气血理论,其方药临床实用性较强,治疗疑难病,常获较好疗效,笔者在临床中学习取得一定体会,列举病案4例。     

Accuracy and reliability of forensic handwriting comparisons

Forensic handwriting examination involves the comparison of writing samples by forensic document examiners (FDEs) to determine whether or not they were written by the same person. Here we report the results of a large-scale study conducted to assess the accuracy and reliability of handwriting comparison conclusions. Eighty-six practicing FDEs each conducted up to 100 handwriting comparisons, resulting in 7,196 conclusions on 180 distinct comparison sets, using a five-level conclusion scale. Erroneous “written by” conclusions (false positives) were reached in 3.1% of the nonmated comparisons, while 1.1% of the mated comparisons yielded erroneous “not written by” conclusions (false negatives). False positive rates were markedly higher for nonmated samples written by twins (8.7%) compared to nontwins (2.5%). Notable associations between training and performance were observed: FDEs with less than 2 y of formal training generally had higher error rates, but they also had higher true positive and true negative rates because they tended to provide more definitive conclusions; FDEs with at least 2 y of formal training were less likely to make definitive conclusions, but those definitive conclusions they made were more likely to be correct (higher positive predictive and negative predictive values). We did not observe any association between writing style (cursive vs. printing) and rates of errors or incorrect conclusions. This report also provides details on the repeatability and reproducibility of conclusions, and reports how conclusions are affected by the quantity of writing and the similarity of content.

Forensic science is under scrutiny, particularly for pattern-based disciplines in which source conclusions are reported. The National Research Council report Strengthening Forensic Science in the United States: A Path Forward (1) stated that “The scientific basis for handwriting comparisons needs to be strengthened” and noted that “there has been only limited research to quantify the reliability and replicability of the practices used by trained document examiners.” The President’s Council of Advisors on Science and Technology (PCAST) report Forensic Science in Criminal Courts: Ensuring Scientific Validity of Feature-Comparison Methods (2) expressed concerns regarding the validity and reliability of conclusions made by forensic examiners, and called for empirical testing: “The only way to establish the scientific validity and degree of reliability of a subjective forensic feature-comparison method—that is, one involving significant human judgment—is to test it empirically by seeing how often examiners actually get the right answer. Such an empirical test of a subjective forensic feature-comparison method is referred to as a ‘black-box test.’” The National Commission on Forensic Science also called for such testing (3). Although the accuracy and reliability of conclusions made by forensic document examiners (FDEs) have been the focus of multiple studies over the years (4–10), the designs of those studies are notably different from this study (and from PCAST’s recommendations), and therefore the resulting rates are not directly comparable (in particular, when comparing open-set to closed-set studies, comparing studies based on one-to-one vs. one-to-many examinations, and comparing studies that use notably different conclusion scales; see SI Appendix, Appendix B for a summary).This study was conducted to provide data that can be used to assess the scientific validity of handwriting comparisons, for use by policy makers, laboratory managers, the legal community, and FDEs. This study follows the approach used in the previous FBI Laboratory–Noblis latent print black box study (11) and later recommended by the PCAST report. The design utilizes open-set, one-to-one document comparisons to evaluate the conclusions reached by practicing FDEs when comparing writing samples selected to be broadly comparable to casework. The primary purposes of the study are to measure the accuracy of conclusions by FDEs when comparing handwriting samples and to assess reliability by measuring the reproducibility (interexaminer variability) and repeatability (intraexaminer variability) of those conclusions. Secondary purposes include reporting any associations between the accuracy of the decisions in this study, factors related to the participants (such as training or experience), and factors related to the samples (such as quantity of writing, comparability of content, limitations, or style of writing).     

Research on Hyperparameter Optimization of Concrete Slump Prediction Model Based on Response Surface Method

In this paper, eight variables of cement, blast furnace slag, fly ash, water, superplasticizer, coarse aggregate, fine aggregate and flow are used as network input and slump is used as network output to construct a back-propagation (BP) neural network. On this basis, the learning rate, momentum factor, number of hidden nodes and number of iterations are used as hyperparameters to construct 2-layer and 3-layer neural networks respectively. Finally, the response surface method (RSM) is used to optimize the parameters of the network model obtained previously. The results show that the network model with parameters obtained by the response surface method (RSM) has a better coefficient of determination for the test set than the model before optimization, and the optimized model has higher prediction accuracy. At the same time, the model is used to evaluate the influencing factors of each variable on slump. The results show that flow, water, coarse aggregate and fine aggregate are the four main influencing factors, and the maximum influencing factor of flow is 0.875. This also provides a new idea for quickly and effectively adjusting the parameters of the neural network model to improve the prediction accuracy of concrete slump.     

Age-specific influences of refractive error and illuminance on pupil diameter

To assess the most influential factor for pupil diameter changes among age, illuminance, and refractive state and reestablish the optimal procedures for clinical applications based on refractive state and illuminance for different age groups.The study was an observational study (repeated measure study). Participants included 219 Korean adults aged 20 to 69 years. Pupil diameters were measured using a pupilometer under scotopic, mesopic-low, and mesopic-high lighting conditions. Factor interactions among age, illuminance, and refractive state were evaluated using mixed linear model and chi-square automated interaction detection.Illuminance mainly contributed to variations in pupil diameter of participants over 50 years, whereas the refractive state was the dominant controlling factor for the pupil variation in participants below 50 years. For more generalized application, the pupil diameter decreased with older age and brighter illuminance (P < .001, inverse correlation, all comparisons). The mean pupil diameter was significantly higher in myopes and emmetropes than in hyperopes (P < .001). Pupil diameter variation modeled using the mixed model confirmed age, illuminance, and refractive error as significant factors (P < .001).Accounting for the interactions among age, illuminance, and refractive error and establishing their hierarchical dominance can be generalized using the chi-square automated interaction detection method and mixed model. Promoting age-dependent consideration for both illuminance and refractive state is necessary when pupil diameters play significant roles in clinical and manufacturing circumstances.     

Dosimetric effect of set-up error in accelerator-based boron neutron capture therapy for head and neck cancer

The dosimetric effect of set-up error in boron neutron capture therapy (BNCT) for head and neck cancer remains unclear. In this study, we analyzed the tendency of dose error by treatment location when simulating the set-up error of patients. We also determined the tolerance level of the set-up error in BNCT for head and neck cancer. As a method, the distal direction was shifted with an interval of 2.5 mm, from 0.0 mm to +20.0 mm and compared with the dose at the reference position. Similarly, the horizontal direction and vertical direction were shifted, with an interval of 5.0 mm, from −20.0 mm to +20.0 mm. In addition, cases with 3.0 mm and 5.0 mm simultaneous shifts in all directions were analyzed as the worst-case scenario. The dose metrics of the minimum dose of the tumor and the maximum dose of the mucosa were evaluated. From unidirectional set-up error analysis, in most cases, the set-up errors with dose errors within ±5% were Δdistal < +2.5 mm, Δhorizontal < ±5.0 mm and Δvertical < ±5.0 mm. In the simulation of 3.0 mm shifts in all directions, the errors in the minimum tumor dose and maximum mucosal dose were −3.6% ±1.4% (range, −5.4% to −0.6%) and 2% ±1.4% (range, 0.4% to 4.5%), respectively. From these results, if the set-up error was within ±3.0 mm in each direction, the dose errors of the tumor and mucosa could be suppressed within approximately ±5%, which is suggested as a tolerance level.     

美国的医疗差错报告制度及借鉴意义

准确掌握和统计医疗差错信息,对促进医疗安全有着积极意义.简要地回顾了美国医疗差错报告制度实行的概况,希望对促进我国医疗事故报告制度的建设有所借鉴.