Morphology cluster and prediction of growth of human brain pyramidal neurons

Predicting neuron growth is valuable to understand the morphology of neurons, thus it is helpful in the research of neuron classification. This study sought to propose a new method of predicting the growth of human neurons using 1 907 sets of data in human brain pyramidal neurons obtained from the website of NeuroMorpho.Org. First, we analyzed neurons in a morphology field and used an expectation-maximization algorithm to specify the neurons into six clusters. Second, naive Bayes classifier was used to verify the accuracy of the expectation-maximization algorithm. Experiment results proved that the cluster groups here were efficient and feasible. Finally, a new method to rank the six expectation-maximization algorithm clustered classes was used in predicting the growth of human pyramidal neurons.     

Asymptotic accuracy of Bayesian estimation for a single latent variable

In data science and machine learning, hierarchical parametric models, such as mixture models, are often used. They contain two kinds of variables: observable variables, which represent the parts of the data that can be directly measured, and latent variables, which represent the underlying processes that generate the data. Although there has been an increase in research on the estimation accuracy for observable variables, the theoretical analysis of estimating latent variables has not been thoroughly investigated. In a previous study, we determined the accuracy of a Bayes estimation for the joint probability of the latent variables in a dataset, and we proved that the Bayes method is asymptotically more accurate than the maximum-likelihood method. However, the accuracy of the Bayes estimation for a single latent variable remains unknown. In the present paper, we derive the asymptotic expansions of the error functions, which are defined by the Kullback–Leibler divergence, for two types of single-variable estimations when the statistical regularity is satisfied. Our results indicate that the accuracies of the Bayes and maximum-likelihood methods are asymptotically equivalent and clarify that the Bayes method is only advantageous for multivariable estimations.     

Penalization,bias reduction,and default priors in logistic and related categorical and survival regressions

Penalization is a very general method of stabilizing or regularizing estimates, which has both frequentist and Bayesian rationales. We consider some questions that arise when considering alternative penalties for logistic regression and related models. The most widely programmed penalty appears to be the Firth small‐sample bias‐reduction method (albeit with small differences among implementations and the results they provide), which corresponds to using the log density of the Jeffreys invariant prior distribution as a penalty function. The latter representation raises some serious contextual objections to the Firth reduction, which also apply to alternative penalties based on t‐distributions (including Cauchy priors). Taking simplicity of implementation and interpretation as our chief criteria, we propose that the log‐F(1,1) prior provides a better default penalty than other proposals. Penalization based on more general log‐F priors is trivial to implement and facilitates mean‐squared error reduction and sensitivity analyses of penalty strength by varying the number of prior degrees of freedom. We caution however against penalization of intercepts, which are unduly sensitive to covariate coding and design idiosyncrasies. Copyright © 2015 John Wiley & Sons, Ltd.     

Quantitative evaluation of the diagnostic thinking process in medical students

OBJECTIVE: To explore the diagnostic thinking process of medical students. SUBJECTS AND METHODS: Two hundred twenty-four medical students were presented with 3 clinical scenarios corresponding to high, low, and intermediate pre-test probability of coronary artery disease. Estimates of test characteristics of the exercise stress test, and pre-test and post-test probability for each scenario were elicited from the students (intuitive estimates) and from the literature (reference estimates). Post-test probabilities were calculated using Bayes' theorem based upon the intuitive estimates (Bayesian estimates of post-test probability) and upon the reference estimates (reference estimates of post-test probability). The differences between the reference estimates and the intuitive estimates, and between Bayesian estimates and the intuitive estimates were used for assessing knowledge of test characteristics, and ability of estimating pre-test and post-test probability of disease. RESULTS: Medical students could not rule out disease in low or intermediate pre-test probability settings, mainly because of poor pre-test estimates of disease probability. They were also easily confused by test results that differed from their anticipated results, probably because of their inaptitude in applying Bayes' theorem to real clinical situations. These diagnostic thinking patterns account for medical students or novice physicians repeating unnecessary examinations. CONCLUSIONS: Medical students' diagnostic ability may be enhanced by the following educational strategies: 1) emphasizing the importance of ruling out disease in clinical practice, 2) training in the estimation of pre-test disease probability based upon history and physical examination, and 3) incorporation of the Bayesian probabilistic thinking and its application to real clinical situations.     

验前概率联合冠脉CT造影对于稳定型冠心病的诊断价值

目的：比较升级的Diamond-Forrester法(updated Diamond-Forrester method,UDFM)和Duke临床评分(Duke clinical score,DCS)对于冠心病的评估准确性,并进一步分析验前概率与冠脉CT造影(computed tomographic coronary angiography, CTCA)联合应用的诊断准确性。方法纳入2012年1月-2013年12月因稳定型心绞痛在解放军总医院心内科先后行CTCA和传统冠状动脉造影(conventional coronary angiography,CCA)的患者523例,分别用UDFM和DCS估算每例患者患冠心病的验前概率。以CCA结果为金标准,分析验前概率、CTCA及两者联合应用对冠心病的诊断准确性。理论验后概率根据贝叶斯公式进行计算。结果523例患者中有385例(74%)CCA结果为阳性。与UDFM相比,DCS将更多的CCA结果阳性患者分入高验前概率组(46%vs 23%,P＜0.0001)。DCS的ROC曲线下面积明显大于UDFM[0.77(0.73,0.82)vs 0.71(0.66,0.77),P=0.0009]。根据DCS估算结果划分的低、中和高3个验前概率亚组中,CTCA的敏感性、特异性、阳性预测值及阴性预测值分别是94%、98%和97%,94%、87%和55%,91%、94%和93%及96%、96%和77%。中验前概率亚组的理论验后概率十分接近实际验后概率(阳性：94.7%vs 93.6%,阴性：3.7%vs 4.0%)。结论对于稳定型心绞痛患者,DCS比UDFM更适用于冠心病验前概率的估算。将按DCS估算的验前概率与CTCA联合应用,能够有效提高CTCA的诊断准确性,并避免过度检查。     

Trait-mediated assembly processes predict successional changes in community diversity of tropical forests

Interspecific differences in relative fitness can cause local dominance by a single species. However, stabilizing interspecific niche differences can promote local diversity. Understanding these mechanisms requires that we simultaneously quantify their effects on demography and link these effects to community dynamics. Successional forests are ideal systems for testing assembly theory because they exhibit rapid community assembly. Here, we leverage functional trait and long-term demographic data to build spatially explicit models of successional community dynamics of lowland rainforests in Costa Rica. First, we ask what the effects and relative importance of four trait-mediated community assembly processes are on tree survival, a major component of fitness. We model trait correlations with relative fitness differences that are both density-independent and -dependent in addition to trait correlations with stabilizing niche differences. Second, we ask how the relative importance of these trait-mediated processes relates to successional changes in functional diversity. Tree dynamics were more strongly influenced by trait-related interspecific variation in average survival than trait-related responses to neighbors, with wood specific gravity (WSG) positively correlated with greater survival. Our findings also suggest that competition was mediated by stabilizing niche differences associated with specific leaf area (SLA) and leaf dry matter content (LDMC). These drivers of individual-level survival were reflected in successional shifts to higher SLA and LDMC diversity but lower WSG diversity. Our study makes significant advances to identifying the links between individual tree performance, species functional traits, and mechanisms of tropical forest succession.Quantifying the relative importance of mechanisms that drive community assembly remains a central challenge in ecology. Interspecific variation in ecological strategies is considered a major driver of community assembly and has been classified by Chesson (1) into relative fitness (i.e., per capita population growth rate) differences and stabilizing niche differences (2). These processes act concurrently, and their importance may vary over space and time (3). However, the simultaneous effects of different assembly mechanisms on community dynamics have not been well-characterized, particularly in diverse communities such as tropical forests. High dynamism of vegetation composition during tropical forest succession creates an ideal opportunity to investigate the drivers of community assembly.Interspecific niche and fitness differences can be characterized through the lens of interspecific functional trait variation, an approach that can shed light on drivers of community functional composition and dynamics (2, 4, 5). Traits may mediate niche and fitness differences in at least four ways (Fig. 1). First, interspecific trait variation can be correlated with fitness independent of neighbor density, such that species possessing traits associated with the highest fitness should exclude species with unfavorable traits (1, 2) (1 in Fig. 1). Second, traits may be associated with a species’ sensitivity to neighbor density (i.e., a trait × crowding interaction effect on fitness). As a result, certain trait values may have relatively low fitness under high crowding (6–9) (2 in Fig. 1). For example, species with low wood specific gravity (WSG) might have higher fitness at the initiation of succession but be disadvantaged later in succession because of sensitivity to crowding. Third, negative density effects of neighbors may be asymmetric between species and dependent on hierarchies (i.e., species with favorable traits experience weaker negative density effects of neighbors with unfavorable traits, generating relative fitness differences) (10) (3 in Fig. 1). For example, species with high WSG may have stronger negative density effects on neighbors with low WSG than vice versa (10). Fourth, trait variation may be related to local niche differences between neighbors, such that greater trait differences weaken negative density effects of neighbors and promote stable coexistence of functionally diverse neighbors (11, 12) (4 in Fig. 1). Overall, traits associated with fitness differences (1–3 in Fig. 1) are expected to decrease in diversity over time, whereas traits associated with stabilizing niche differences (4 in Fig. 1) are expected to increase in diversity, assuming no trait bias in immigration. Gaining a more nuanced, complete, and predictive understanding of community assembly requires that we quantify the effects of these assembly processes on species demography and the associated changes at the community level (13, 14).Open in a separate windowFig. 1.Illustration of the four mechanisms of trait-mediated assembly included in our models. Assembly may be driven by species differences in (1) survival independent of crowding by neighbors, (2) response to increased crowding, (3) competitive hierarchies, and (4) local niche. All four processes may be revealed through the lens of functional trait variation (the spectrum from yellow to green) and its effects on mortality (black Xs). Note that the color schemes are not meant to be mutually compatible. In 1, the green color is associated with greater fitness (e.g., because of higher survival) compared with yellow, independent of neighborhood crowding. (2) Green traits have lower sensitivity to crowding relative to yellow traits (irrespective of neighbors'' traits, which are shown in gray). (3) Species have trait hierarchies. Here, green is dominant (i.e., greener species always have greater negative effect on the performance of yellower neighbors than vice versa). (a) Because their traits are very different, the green species has a stronger competitive effect on the yellow species compared with (b) the competitive effect of the yellow-green species on the yellow species. (4) In contrast, when trait variation is associated with stabilizing niche differences between neighbors, negative density effects are experienced similarly by both species. (a) Neighbors with greater trait-associated niche difference (green vs. yellow) have a weaker competitive effect relative to (b) species with less difference in traits (green vs. yellow-green).Successional tropical forests exhibit rapid community assembly and thus, provide an ideal system for testing assembly theory (15). High species richness and elevated tree growth and mortality rates relative to old-growth forests contribute to rapid species turnover and increase the likelihood of detecting assembly processes across succession (16). As succession proceeds, increased crowding alters local resource availability, which may drive species turnover (17–19). Early successional forests are typically dominated by species with acquisitive traits, such as low WSG and high specific leaf area (SLA), which enable rapid growth, resource capture, and high fitness under conditions of high resource availability (17, 20, 21). In contrast, traits that tend to dominate older forests [e.g., dense wood and tough leaves (22, 23)] are thought to promote long-term survival and fitness under high crowding and low resource availability (17, 24). Trait diversity is also expected to change as succession proceeds, although the direction and mechanisms of diversity changes remain unclear (23). Despite considerable previous efforts, few researchers have tested these hypotheses using demographic data in diverse systems.We use a long-term dataset of tropical forest succession to disentangle how trait-mediated processes drive community dynamics. Spatially explicit longitudinal studies of individual performance offer a powerful approach to reveal drivers of community dynamics (9, 12, 14, 25–27). Empirical studies of functional community assembly have typically compared static community patterns across sites using aggregated trait metrics (28–30). These studies assume that community patterns are the result of prior assembly processes. However, static and aggregated patterns provide limited capability to distinguish between multiple, often opposing assembly processes (14, 31).Our novel approach simultaneously quantifies the relative importance of multiple assembly processes and links these processes to contrasting effects on functional diversity. We use trait data for over 200 tree species, and we develop spatially explicit statistical models of tree survival over 15 y across eight 1-ha forest plots at diverse stages of succession in lowland wet forests of Costa Rica (SI Appendix, Table S1). We ask three central questions about trait-mediated effects on tree survival rates, a major component of fitness, and successional community dynamics.

• i)What are the simultaneous effects and relative importance of four trait-mediated assembly processes on tree survival? Specifically, we ask four subquestions about the processes.
  • i.i) How are functional traits related to interspecific variation in average survival?
  • i.ii) How do trait relationships with survival change with variation in neighborhood crowding?
  • i.iii) Do competitive interactions depend on trait hierarchy, indicating that crowding effects are based on dominance?
  • i.iv) Do competitive interactions with neighbors depend on absolute trait differences between neighbors, suggesting stabilizing niche differences?
• ii)Is the demographic evidence for trait-mediated fitness and niche differences (i) reflected in community-level changes in trait diversity across successional stages? We expect that traits associated with relative fitness (i.e., associated with greater average survival, decreased sensitivity to crowding, and hierarchical dominance) will decrease in diversity over time, whereas traits associated with stabilizing niche differences will increase in diversity during forest succession.
• iii)Is the demographic evidence for trait-mediated fitness differences reflected in functional differences between second-growth specialists and old-growth specialists? We expect that traits associated with greater relative fitness will be more strongly associated with old-growth specialists compared with second-growth specialists.

To answer these questions, we built hierarchical Bayes models of community-wide stem survival, which include parameters for each assembly process in questions i.i–i.iv (12, 27) (details in Methods). We fit models for each of three functional traits associated with resource use and life history: SLA (defined as leaf area per unit dry mass), leaf dry matter content (LDMC; defined as leaf dry mass over leaf fresh mass), and WSG (defined as the density of wood relative to the density of water). These traits represent leading axes of ecological variation among tropical tree species that have been previously implicated in interspecific variation in resource use efficiency, species interactions, and life history strategies (32–34). SLA represents a major axis of variation between rapid resource acquisition for species with high SLA vs. conservative strategies with low tissue turnover for species with low SLA (32, 35). Species with high LDMC have lower leaf protein and reduced ability to exploit resource-rich environments but better performance under low resources and drought (7, 34, 36, 37). WSG is associated with a tradeoff between rapid growth rates for species with low WSG and high structural support and resistance to natural enemies for species with high WSG (9, 33).     

How to use clinical signs and symptoms to estimate the probability of limb ischaemia in patients with a diabetic foot ulcer

Assessment of ischaemia and interventions to improve perfusion are key elements in the management of the diabetic foot ulcer to achieve wound healing. This article will review, analyse and interpret the value of clinical information in determining the likelihood of limb ischaemia and thereby the need for referral to a vascular specialist. I conducted an historical review of the genesis of several currently recommended clinical signs and their diagnostic properties in the assessment of limb ischaemia. Changes in limb ischaemia probability based on such results were calculated using Bayes theorem, and the use of such probabilities is discussed in the context of the threshold approach to clinical decision making. Some clinical signs have negligible value in altering probability of limb ischaemia, possibly because they were advocated by Buerger for the diagnosis of thromboangiitis obliterans, an occlusive vascular disease of a different pathophysiology than atherosclerosis. Pedal pulse palpation, the most widely studied clinical sign, will marginally change a pre‐test probability of ischaemia of 50% to 76% if positive (abnormal pulses) and to 36% if negative (normal pulses). Higher or lower pre‐test probabilities of ischaemia will change the post‐test probabilities such that these are too low or high to rule in or rule out ischaemia, respectively. Individual clinical signs convey little information regarding the presence of limb ischaemia but may have some value in combination or with pre‐test probability near 50% in the assessment of ischaemia and the decision to refer for a vascular consultation.     

Point process modelling of the Afghan War Diary

Modern conflicts are characterized by an ever increasing use of information and sensing technology, resulting in vast amounts of high resolution data. Modelling and prediction of conflict, however, remain challenging tasks due to the heterogeneous and dynamic nature of the data typically available. Here we propose the use of dynamic spatiotemporal modelling tools for the identification of complex underlying processes in conflict, such as diffusion, relocation, heterogeneous escalation, and volatility. Using ideas from statistics, signal processing, and ecology, we provide a predictive framework able to assimilate data and give confidence estimates on the predictions. We demonstrate our methods on the WikiLeaks Afghan War Diary. Our results show that the approach allows deeper insights into conflict dynamics and allows a strikingly statistically accurate forward prediction of armed opposition group activity in 2010, based solely on data from previous years.     

Rapid exclusion or confirmation of heparin-induced thrombocytopenia: a single-center experience with 1,291 patients

Background

The current gold-standard for diagnosing heparin-induced thrombocytopenia is the detection of platelet-activating antibodies by means of functional assays which, since they are time consuming and not widely available, are not suited to guiding acute treatment decisions. The objective of our study was to assess the ability of more rapid immunoassays to predict the presence of functionally relevant anti-platelet factor 4/heparin-antibodies.

Design and Methods

We analyzed 1,291 of 1,383 (93.4%) patients consecutively evaluated for suspected heparin-induced thrombocytopenia at our institution. Clinical pre-test probability was defined by the 4T-score. Anti-platelet factor 4/heparin-antibodies were measured with three immunoassays (ID-H/PF4-PaGIA, Asserachrom-HPIA, and GTI-PF4) and their functional relevance was assessed by a two-point heparin-induced platelet aggregation test. Performance of the immunoassays was evaluated by receiver operating characteristic analysis.

Results

Among 1,291 patients, 96 (7.4%) had a positive heparin-induced platelet aggregation-test: 7 of 859 (0.8%) with a low, 50 of 358 (14.0%) with an intermediate, and 39 of 74 (52.7%) with a high 4T-score. Receiver operating characteristics analysis indicated that best immunoassay thresholds for predicting a positive platelet aggregation test were: Titer of 4 or more (ID-H/PF4-PaGIA), optical density more than 0.943 (Asserachrom-HPIA) and more than 1.367 (GTI-PF4). A 100% negative predictive value was observed at the following thresholds: Titer of 1 or under (ID-H/PF4-PaGIA), optical density less than 0.300 (Asserachrom-HPIA) and less than 0.870 (GTI-PF4). A 100% positive predictive value was reached only by ID-H/PF4-PaGIA, at titers of 32 or over. Positive and negative likelihood ratios were calculated for results between the thresholds with 100% negative or positive predictive value.

Conclusions

We show that: i) negative and weak positive results of immunoassays detecting anti-platelet factor 4/heparin-antibodies exclude heparin-induced thrombocytopenia; ii) anti-platelet factor 4/heparin-antibody titers of 32 or over (ID-H/PF4-PaGIA) have a 100% positive predictive value for functionally relevant antibodies; iii) combining the clinical pre-test probability with the likelihood ratio of intermediate immunoassay results allows assessment of post-test probability for heparin-induced thrombocytopenia in individual patients.     

Predicting negligence in female sterilization failure using time interval to sterilization failure: analysis of 131 cases

BACKGROUND: Sterilization failure due to 'tubal non-occlusion' or 'wrong structure sterilization' is considered negligent, whereas 'spontaneous tubal recanalization' or 'fistula formation' is considered non-negligent. We examined whether interval to pregnancy failure was predictive of a negligent rather non-negligent failure mechanism. We aim to test this hypothesis in a selected population series of known mechanisms of sterilization failure and their time interval to failure. METHODS: Analyses of 131 failed sterilizations pooled from UK (NHS Litigation Authority, Medical Protection Society and our hospital), Australia and a qualitative systematic review. RESULTS: We identified 88 negligent and 43 non-negligent sterilization failures. Filshie and ring methods failed earlier than diathermy and Pomeroy methods. Sterilization failure occurred significantly earlier in negligent than non-negligent failure mechanisms [median failure intervals 7.0 versus 12.0 months; Hazard ratio (2.35 95% CI 1.31-4.21)]. Knowing that sterilization failure occurred early, increased the probability that the failure mechanism was likely to be negligent rather than non-negligent. CONCLUSIONS: A short interval to failure is suggestive of a negligent failure mechanism. There is less certainty in the predictive value of longer time intervals on the mechanism of failure due to a paucity of cases. A national register of failed sterilizations that have been systematically investigated is needed to improve our understanding of negligent and non-negligent failure mechanisms.