SBGN Bricks Ontology as a tool to describe recurring concepts in molecular networks.

A comprehensible representation of a molecular network is key to communicating and understanding scientific results in systems biology. The Systems Biology Graphical Notation (SBGN) has emerged as the main standard to represent such networks graphically. It has been implemented by different software tools, and is now largely used to communicate maps in scientific publications. However, learning the standard, and using it to build large maps, can be tedious. Moreover, SBGN maps are not grounded on a formal semantic layer and therefore do not enable formal analysis. Here, we introduce a new set of patterns representing recurring concepts encountered in molecular networks, called SBGN bricks. The bricks are structured in a new ontology, the Bricks Ontology (BKO), to define clear semantics for each of the biological concepts they represent. We show the usefulness of the bricks and BKO for both the template-based construction and the semantic annotation of molecular networks. The SBGN bricks and BKO can be freely explored and downloaded at sbgnbricks.org.

External validation of the R2eD AVM scoring system to assess rupture risk in pediatric AVM patients.

OBJECTIVE: The assessment of hemorrhagic risk is of central importance in the management of pediatric brain arteriovenous malformations (AVMs). A recently published scoring system, the R2eD AVM (race, exclusive deep location or not, AVM size < 3 or ≥ 3, venous drainage exclusively deep or not, and monoarterial feeding or >1 arterial feeders) considers patient race and AVM location, size, venous drainage, and arterial supply and was successfully externally validated for use in adults to predict the risk of AVM hemorrhagic presentation. In this study the authors sought to externally validate the R2eD AVM score for prediction of hemorrhagic risk in the pediatric AVM population. METHODS: A pediatric database at Boston Children's Hospital was retrospectively reviewed for all patients with a diagnosis of intracranial AVM. Exclusion criteria included age > 21 years, multiple AVMs, and incomplete clinical/radiographic data. Demographic data and R2eD AVM score calculations were collected for all patients. Univariate binary logistic regression and multivariate stepwise backward elimination models were used to determine factors associated with hemorrhagic presentation. RESULTS: A total of 212 AVMs were identified in 212 patients with vascular anomalies from 1995 to 2021, and 144 patients met the inclusion criteria (74 [51.4%] male, 111 [77.1%] White), of whom 87 (60.4%) patients presented with rupture and 122 (84.7%) underwent resection. The mean age at surgery was 12 years (range 3 months to 20 years). The R2eD AVM scoring system was applied to each patient. The score components of size < 3 cm and exclusive deep venous drainage were significantly associated with rupture risk (p < 0.05). The complete model for the R2eD AVM score had an area under the curve of 0.671 (95% CI 0.586-0.757). CONCLUSIONS: This study demonstrated poor external validity of the R2eD AVM score in predicting pediatric AVM rupture risk. The results suggest that future studies are warranted to determine a better scoring method to capture pediatric rupture risk, given the significant differences in clinical presentation in pediatric compared with adult AVM patients.

Positioning Transclival Tumor-Treating Fields for the Treatment of Diffuse Intrinsic Pontine Gliomas.

Diffuse intrinsic pontine glioma (DIPG) carries an extremely poor prognosis, with 2-year survival rates of <10% despite the maximal radiation therapy. DIPG cells have previously been shown to be sensitive to low-intensity electric fields in vitro. Accordingly, we sought to determine if the endoscopic endonasal (EE) implantation of an electrode array in the clivus would be feasible for the application of tumor-treating fields (TTF) in DIPG. Anatomic constraints are the main limitation in pediatric EE approaches. In our Boston Children's Hospital's DIPG cohort, we measured the average intercarotid distance (1.68 ± 0.36 cm), clival width (1.62 ± 0.19 cm), and clival length from the base of the sella (1.43 ± 0.69 cm). Using a linear regression model, we found that only clival length and sphenoid pneumatization were significantly associated with age (R2 = 0.568, p = 0.005 *; R2 = 0.605, p = 0.0002 *). Critically, neither of these parameters represent limitations to the implantation of a device within the dimensions of those currently available. Our findings confirm that the anatomy present within this age group is amenable to the placement of a 2 × 1 cm electrode array in 94% of patients examined. Our work serves to demonstrate the feasibility of implantable transclival devices for the provision of TTFs as a novel adjunctive therapy for DIPG.

Extended Thromboprophylaxis in Hospitalized Patients with Heart Failure: A Post Hoc Analysis of the MAGELLAN Study.

This post hoc subgroup analysis examined efficacy and safety outcomes with extended thromboprophylaxis rivaroxaban compared with in-hospital enoxaparin in 2,078 patients from the MAGELLAN study who had a hospitalization for heart failure or a history of heart failure and a lower risk of bleeding. A significant 36% reduction in the composite endpoint of asymptomatic proximal deep vein thrombosis (DVT) in the lower extremity, symptomatic DVT in the lower extremity (proximal or distal), symptomatic nonfatal pulmonary embolism, and venous thromboembolism-related death was observed with rivaroxaban. Major bleeding was low in both groups and not significantly increased with rivaroxaban.

Benefit-Risk Assessment of Rivaroxaban for Extended Thromboprophylaxis After Hospitalization for Medical Illness.

Background Venous thromboembolism (VTE) often occurs after hospitalization in medically ill patients, but the population benefit-risk of extended thromboprophylaxis remains uncertain. Methods and Results The MARINER (Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk) study (NCT02111564) was a randomized double-blind trial that compared thromboprophylaxis with rivaroxaban 10 mg daily versus placebo for 45 days after hospital discharge in medically ill patients with a creatinine clearance ≥50 mL/min. The benefit-risk balance in this population was quantified by calculating the between-treatment rate differences in efficacy and safety end points per 10 000 patients treated. Clinical characteristics of the study population were consistent with a hospitalized medical population at risk for VTE. Treating 10 000 patients with rivaroxaban resulted in 32.5 fewer symptomatic VTE and VTE-related deaths but was associated with 8 additional major bleeding events. The treatment benefit was driven by the prevention of nonfatal symptomatic VTE (26 fewer events). There was no between-treatment difference in the composite of critical site or fatal bleeding. Conclusions Extending thromboprophylaxis with rivaroxaban for 45 days after hospitalization provides a positive benefit-risk balance in medically ill patients at risk for VTE who are not at high risk for bleeding. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT02111564.

Association Between Asymptomatic Proximal Deep Vein Thrombosis and Mortality in Acutely Ill Medical Patients.

Background Asymptomatic proximal deep vein thrombosis (DVT) is an end point frequently used to evaluate the efficacy of anticoagulant thromboprophylaxis in medical patients. Recently, the clinical relevance of asymptomatic DVT has been challenged. Methods and Results The objective of this study was to evaluate the relationship between asymptomatic proximal DVT and all-cause mortality (ACM) using a cohort analysis of a randomized trial for the prevention of venous thromboembolism (VTE) in acutely ill medical patients. Patients who received at least 1 dose of study drug and had an adequate compression ultrasound examination of the legs on either day 10 or day 35 were categorized into 1 of 3 cohorts: no VTE, asymptomatic proximal DVT, or symptomatic DVT. Cox proportional hazards model, with adjustment for significant independent predictors of mortality, were used to compare the incidences of ACM. Of the 7036 patients, 6776 had no VTE, 236 had asymptomatic DVT, and 24 had symptomatic VTE. The incidence of ACM was 4.8% in patients without VTE. Both asymptomatic proximal DVT (mortality, 11.4%; hazard ratio [HR], 2.31; 95% CI, 1.52-3.51; P<0.0001) and symptomatic VTE (mortality, 29.2%; HR, 9.42; 95% CI, 4.18-21.20; P<0.0001) were independently associated with significant increases in ACM. The analysis was post hoc, and ultrasound results were not available for all patients. Adjustment for baseline variables significantly associated with ACM may not fully compensate for differences. Conclusions Asymptomatic proximal DVT is associated with higher ACM than no VTE and remains a relevant end point to evaluate the efficacy of anticoagulant thromboprophylaxis in medical patients. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00571649.

Thromboprophylaxis with Rivaroxaban in Acutely Ill Medical Patients with Renal Impairment: Insights from the MAGELLAN and MARINER Trials.

Patients with renal impairment are at higher risk of thrombosis and bleeding than those with normal renal function. The optimal rivaroxaban dose for thromboprophylaxis in acutely ill medical patients with renal impairment is unknown. MARINER and MAGELLAN were multicenter, randomized clinical trials of rivaroxaban in acutely ill medical patients. Efficacy and safety outcomes in patients with renal impairment in MARINER (7.5 mg once daily) were compared with those in patients with normal renal function in MARINER (10 mg once daily) and in a subpopulation of MAGELLAN that excluded patients at high risk for bleeding at baseline (10 mg once daily). Compared with enoxaparin/placebo in the MAGELLAN subpopulation, the relative risk (RR) of symptomatic venous thromboembolism (VTE) and VTE-related death with rivaroxaban 10 mg in patients with renal impairment (RR = 0.62; 95% confidence interval [CI] 0.27-1.44) was similar to that in those with normal renal function (RR = 0.78; 95% CI 0.44-1.40), while in MARINER, the 7.5 mg dose did not reduce the risk in patients with renal impairment (hazard ratio = 1.00; 95% CI 0.52-1.92). Major bleeding with rivaroxaban 10 mg once daily was higher in patients with renal impairment than in those with normal renal function in MAGELLAN (1.54% vs. 0.98%) and in the MAGELLAN subpopulation (0.94% vs. 0.61%). At a dose of 10 mg once daily, rivaroxaban is effective for thromboprophylaxis in acutely ill medical patients with impaired or normal renal function. The safety of this regimen is enhanced without loss of efficacy by excluding patients at high risk for bleeding, but not by using a reduced-dose strategy. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00571649 for the MAGELLAN trial, NCT02111564 for the MARINER trial.

Evaluation of a new disposable silicon limbal relaxing incision knife by experienced users.

BACKGROUND: Previous research has suggested that the silicon BD Atomic Edge knife has superior performance characteristics when compared to a metal knife and performance similar to diamond knife when making various incisions. This study was designed to determine whether a silicon accurate depth knife has equivalent performance characteristics when compared to a diamond limbal relaxing incision (LRI) knife and superior performance characteristics when compared to a steel accurate depth knife when creating limbal relaxing incision. METHODS: Sixty-five ophthalmic surgeons with limbal relaxing incision experience created limbal relaxing incisions in ex-vivo porcine eyes with silicon and steel accurate depth knives and diamond LRI knives. The ophthalmic surgeons rated multiple performance characteristics of the knives on Visual Analog Scales. RESULTS: The observed differences between the silicon knife and diamond knife were found to be insignificant. The mean ratio between the performance of the silicon knife and the diamond knife was shown to be greater than 90% (with 95% confidence). The silicon knife's mean performance was significantly higher than the performance of the steel knife for all characteristics. (p-value < .05) CONCLUSIONS: For experienced users, the silicon accurate depth knife was found to be equivalent in performance to the diamond LRI knife and superior to the steel accurate depth knife when making limbal relaxing incisions in ex vivo porcine eyes. Disposable silicon LRI knives may be an alternative to diamond LRI knives.

Investigating the role of exogenous cueing on selection history formation.

An abundance of recent empirical data suggest that repeatedly allocating visual attention to task-relevant and/or reward-predicting features in the visual world engenders an attentional bias for these frequently attended stimuli, even when they become task irrelevant and no longer predict reward. In short, attentional selection in the past hinders voluntary control of attention in the present. But do such enduring attentional biases rely on a history of voluntary, goal-directed attentional selection, or can they be generated through involuntary, effortless attentional allocation? An abrupt visual onset triggers such a reflexive allocation of covert spatial attention to its location in the visual field, automatically modulating numerous aspects of visual perception. In this Registered Report, we asked whether a selection history that has been reflexively and involuntarily derived (i.e., through abrupt-onset cueing) also interferes with goal-directed attentional control, even in the complete absence of exogenous cues. To build spatially distinct histories of exogenous selection, we presented abrupt-onset cues twice as often at one of two task locations, and as expected, these cues reflexively modulated visual processing: task accuracy increased, and response times (RTs) decreased, when the cue appeared near the target's location, relative to that of the distractor. Upon removal of these cues, however, we found no evidence that exogenous selection history modulated task performance: task accuracy and RTs at the previously most-cued and previously least-cued sides were statistically indistinguishable. Thus, unlike voluntarily directed attention, involuntary attentional allocation may not be sufficient to engender historically contingent selection biases.

Estimating Biological Characteristics With Virtual Laser Data.

Laser scanning technology is increasingly being used in forensic anthropological research to obtain virtual data for archival purposes and post hoc measurement collection. This research compared the measurement accuracy of two laser scanners-the FARO Focus3D 330X and the FARO Freestyle3D -against traditionally obtained (i.e., by hand) control data (N = 454). Skeletal data were collected to address a novel question: the ability of laser scanning technology to produce measurements useful for biological characteristic estimation, such as sex and stature. Results indicate that both devices produced measurements very similar to control (c. 3-mm average absolute error), but also illuminate a tendency to under-measure. Despite these findings, the virtual data produced sex and stature estimates that varied little from control-produced estimates, signifying the usefulness of virtual data for preliminary biological identification when the skeletal elements are no longer available for physical analysis.

Do group-specific equations provide the best estimates of stature?

An estimate of stature can be used by a forensic anthropologist with the preliminary identification of an unknown individual when human skeletal remains are recovered. Fordisc is a computer application that can be used to estimate stature; like many other methods it requires the user to assign an unknown individual to a specific group defined by sex, race/ancestry, and century of birth before an equation is applied. The assumption is that a group-specific equation controls for group differences and should provide the best results most often. In this paper we assess the utility and benefits of using group-specific equations to estimate stature using Fordisc. Using the maximum length of the humerus and the maximum length of the femur from individuals with documented stature, we address the question: Do sex-, race/ancestry- and century-specific stature equations provide the best results when estimating stature? The data for our sample of 19th Century White males (n=28) were entered into Fordisc and stature was estimated using 22 different equation options for a total of 616 trials: 19th and 20th Century Black males, 19th and 20th Century Black females, 19th and 20th Century White females, 19th and 20th Century White males, 19th and 20th Century any, and 20th Century Hispanic males. The equations were assessed for utility in any one case (how many times the estimated range bracketed the documented stature) and in aggregate using 1-way ANOVA and other approaches. This group-specific equation that should have provided the best results was outperformed by several other equations for both the femur and humerus. These results suggest that group-specific equations do not provide better results for estimating stature while at the same time are more difficult to apply because an unknown must be allocated to a given group before stature can be estimated.

The relationship between cadaver, living and forensic stature: A review of current knowledge and a test using a sample of adult Portuguese males.

The use of cadaver length and forensic stature as a proxy for living standing height has not been scrutinized in detail. In this paper we present a brief review of the current knowledge on the relationship between cadaver, living and forensic stature; assess the magnitude and nature of the differences between these three measures of stature; and investigate the potential impact of these differences in forensic contexts. The study uses a sample of 84 males who were autopsied in 2008 at the National Institute of Legal Medicine and Forensic Sciences (Porto, Portugal), where stature data were collected from three different sources: cadaver stature was obtained from the corpse prior to autopsy, living stature was obtained from military conscription records and forensic stature was obtained from national citizenship identification card records. Descriptive statistics, ANOVA and linear regression are used to analyze the data. The results show that cadaver stature is the highest measure, followed by forensic and by living stature, and the difference between cadaver and living stature is greater than expected (4.3cm). Results also show considerable individual variation in the differences between the three measures of stature and that differences decrease with stature, although only slightly. This study has shown that the difference between cadaver and living stature is greater than previously thought and suggests that previously reported correction factors are a minimum rather than a mean correction. Forensic stature is likely to be incorrectly estimated and can jeopardize identification if methods estimate living rather than forensic stature.

An alternative approach for estimating stature from long bones that is not population- or group-specific.

An accurate and precise estimate of stature can be very useful in the analysis of human remains in forensic cases. A problem with many stature estimation methods is that an unknown individual must first be assigned to a specific group before a method can be applied. Group membership has been defined by sex, age, year of birth, race, ancestry, continental origin, nationality or a combination of these criteria. Univariate and multivariate sex-specific and generic equations are presented here that do not require an unknown individual to be assigned to a group before stature is estimated. The equations were developed using linear regression with a sample (n=244) from the Terry Collection and tested using independent samples from the Forensic Anthropology Databank (n=136) and the Lisbon Collection (n=85). Tests with these independent samples show that (1) the femur provides the best univariate results; (2) the best multivariate equation includes the humerus, femur and tibia lengths; (3) a generic equation that does not require an unknown to first be assigned to a given category provides the best results most often; (4) a population-specific equation does not provide better results for estimating stature; (5) sex-specific equations can provide slightly better results in some cases; however, estimating the wrong sex can have a negative impact on precision and accuracy. With these equations, stature can be estimated independently of age at death, sex or group membership.

Hemostasis during urologic surgery: fibrin sealant compared with absorbable hemostat.

In the United States, fibrin sealants have been used to achieve hemostasis for nearly two decades. Although their clinical utility was first demonstrated in cardiac surgery, their effectiveness and safety have since been demonstrated to extend to a wide array of procedures. Fibrin sealants typically contain two components-fibrinogen and thrombin-that are combined and delivered simultaneously to a target bleeding site in order to achieve hemostasis. However, many commercial formulations contain other additional components, such as antifibrinolytic agents, that have been associated with adverse outcomes. This subanalysis compares the safety and effectiveness of a fibrin sealant versus an absorbable hemostat for achieving hemostasis during urologic procedures with mild to moderate bleeding.

A metric method for sex determination using the hipbone and the femur.

Since the earliest descriptions of the pubis length measurement, it has been recognized that the location of the key landmark in the acetabulum has to be estimated. Using samples from the Terry Collection (n = 324) and the Coimbra Collection (n = 232), the purpose of this research is to, first, test the reproducibility of a new alternative to the traditional measurement of the pubis, and second, to use the best measurement of the pubis along with other measurements of the hipbone and femur to develop a metric method that can be used with confidence to determine the sex of individuals of various geographic origins and time periods. In this study, it was found that, first, the alternative pubis measurement, known as the superior pubis ramus length (SPRL), can be collected more reliably with less mean intra-observer error (0.57%) than the more commonly used manner of measuring the pubis (2.7%). Second, a logistic regression sex determination method using the SPRL, along with other measurements of the hipbone and femur, has an allocation accuracy of 90% to 98.5% (depending on the model used and the manner of testing) across independent samples. Third, traditional racial categorization was irrelevant to the accuracy of the method. Fourth, measurement error greater than 2% in the measurement of the pubis can be the difference between a correct and an incorrect allocation of sex, particularly in borderline cases.

A method for estimating sex using the clavicle, humerus, radius, and ulna.

Sex estimation from skeletal remains can be an important part of preliminary identification. The best source of information for estimating sex is the pelvis but it is not always available for analysis. For these cases, a probabilistic sex estimation method is presented using combinations of standard and alternative measurements of the clavicle, humerus, radius, and ulna. Various equations are developed that are not population specific and that are applicable in various recovery scenarios. The equations were tested using four independent samples (n > 370), including a forensic sample. Allocation accuracies vary by test sample and equation and are consistently good (87.4-97.5%) except for a sample of very small males that show the extreme effects of poverty and mortality bias. For many of the cases where allocation was incorrect, the probabilistic approach indicated that no confidence should be placed in the incorrect allocation and the unknown should be classified as sex indeterminate.

Do century-specific equations provide better estimates of stature? A test of the 19-20th century boundary for the stature estimation feature in Fordisc 3.0.

A sample (n=28) from the Terry Collection was selected to include only White males who were born and had their entire growth and development period before 1900 to assess the effects year of birth have on accuracy and precision when estimating stature. Using the computer application Fordisc 3.0, stature was estimated using the humerus, radius, femur, and tibia equations developed from White males born in the 19th Century and the 20th Century. The 19th Century White male equations did not consistently provide the most precise and accurate estimates of stature. The 20th Century equations provide results that were as good as or slightly better than the 19th Century equations for the humerus, radius and femur. The 20th Century equations provided notably better results for the tibia. There is a great deal of evidence that there are clear positive secular changes in most of North America in the last 100-125 years, but the division commonly advocated in a forensic context at the year 1900 has no positive effect on accuracy or precision when estimating stature.

Latent evidence detection using a combination of near infrared and high dynamic range photography: an example using bloodstains.

In this paper, we use bloodstains to illustrate an approach for identifying latent evidence on dark cloth using near infrared (NIR) photography combined with high dynamic range (HDR) photography techniques. NIR photography alone has been used to capture latent evidence that cannot be seen in normal ambient light. HDR techniques combine multiple bracketed photographs of the same image to increase the dynamic range of the photograph which can provide greater contrast. Using NIR photography alone, we were able to detect a bloodstain up to a 1/16 dilution, an improvement over previous studies. Combining NIR photography with the HDR process resulted in a noticeable increase in visibility up to 1/16 dilution when compared to NIR photographs alone. At 1/32 dilution, we were able to detect bloodstains that were not visible using NIR alone. NIR is a useful tool for imaging latent evidence, and combining NIR with HDR consistently provides better results over NIR alone.