Assessment of local diagnostic reference levels (LDRLS) for full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) mammography in Tamil Nadu, India.

The purpose of this study was to assess local diagnostic reference levels (LDRLs) for full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) mammography in India. Data from 1500 women were collected from five different mammography facilities in major cities in Tamil Nadu, India. The mean of mean glandular dose were used to arrive at an LDRL. The noted mean compressed breast thickness was 55.26 ± 3.4. The recorded mean MGDs for the five centres were 3.1 ± 0.1 and 3.8 ± 0.2 mGy for FFDM and DBT, respectively. The 75th percentile value for all five centers is 3.3 and 4.0 mGy for FFDM and DBT, respectively. The LDRLs found in the current study were also compared with those from earlier studies conducted in other nations, such as the United Kingdom, Malaysia, Morocco, and Ghana. The present study is the first of its kind to determine the LDRL for the FFDM and DBT scanners operating in the Tamil Nadu region, India, and is proposed as a starting point that will allow professionals to evaluate and optimize their practice. Furthermore, similar studies in other regions of India are necessary in order to establish National DRLs.

Outcomes of percutaneous versus surgical tracheostomy in an Australian Quaternary Intensive Care Unit: An entropy-balanced retrospective study.

Background: Studies comparing percutaneous tracheostomy (PT) and surgical tracheostomy (ST) complications in the critically ill patient population with high acuity, complexity, and severity of illness are sparse. This study evaluated the outcomes of elective PT versus ST in such patients managed at a quaternary referral center. Aims: The primary aim was to detect a difference in hospital mortality between the two techniques. The secondary aims were to compare Intensive Care Unit (ICU) mortality, complications (including stoma site, tracheostomy-related, and decannulation complications), ICU and hospital length of stay, and time to decannulation. Methods: This was a single-center retrospective observational study of ICU admission from August 2018 to August 2021. Patients were included if an elective tracheostomy was performed during their ICU admission. Patients with a pre-existing tracheostomy and those who underwent an obligatory tracheostomy requirement (e.g. total laryngectomy) were excluded. Cohorts were matched using Hainmueller's entropy balancing. Binary data were evaluated using logistic regression and continuous data with ordinary least squares regression. Results: 349 patients with a tracheostomy were managed in the ICU during the observation period. They were predominantly males (75% in PT; 67% in ST), with a mean age in the PT and ST group of (47; SD = 18) and (55; SD = 16), respectively. After exclusion, 135 patients remained, with 63 in the PT group and 72 in the ST group. Patients receiving ST were significantly older with a higher Body Mass Index (BMI) than the PT group. There were no significant differences in gender, Acute Physiological And Chronic Health Evaluation (APACHE) III, and the Australian and New Zealand Risk Of Death (ANZROD) between the two groups. There was no difference in hospital mortality between groups (OR 0.91, CI 0.26-3.18, p = 0.88). There were also no differences in ICU mortality, ICU and hospital length of stay, and time to decannulation. PT was associated with a greater likelihood of complications (OR 4.19; 95% CI 1.73-10.13; p < 0.01). PT was associated with a greater risk of complications in those who had this performed early (<10 days of intubation) as well as late (>10 days of intubation). Conclusions: Percutaneous tracheostomy was associated with higher complications compared to surgical tracheostomy. They were related to tracheostomy cuff deflation, stomal site bleeding and infection, sputum plugging, and accidental and failed decannulation. These findings have identified opportunities to improve patient outcomes.

Effect of clustering on Turing instability in complex networks.

Turing instability in complex networks is known to be dependent on the degree distribution, and the necessary conditions for Turing instability have been shown in the literature to have an explicit dependence on the eigenvalues of the Laplacian matrix, which, in turn, depends on the network topology. This study reveals that these conditions are not sufficient, and another global network measure-the nodal clustering-also plays a crucial role. Analytical and numerical results are presented to explain the effects of clustering for several network topologies, ranging from the S1/H2 hyperbolic geometric networks that enable modeling the naturally occurring clustering in real-world networks, as well as the random and scale-free networks, which are obtained as limiting cases of the S1/H2 model. Analysis of the Laplacian eigenvector localization properties in these networks is shown to reveal distinct signatures that enable identifying the so called Turing patterns even in complex networks.

Sleep Disordered Breathing and Neurocognitive Disorders.

Sleep-disordered breathing (SDB), which includes conditions such as obstructive sleep apnea (OSA) and central sleep apnea (CSA), is an independent risk factor for cerebral small vessel disease (CSVD), stroke, heart failure, arrhythmias, and other cardiovascular disorders. The influence of OSA on brain structure and cognitive function has become an essential focus in the heart-brain axis, given its potential role in developing neurocognitive abnormalities. In this review, we found that OSA plays a significant role in the cardio-neural pathway that leads to the development of cerebral small vessel disease and neurocognitive decline. Although data is still limited on this topic, understanding the critical role of OSA in the heart-brain axis could lead to the utilization of imaging modalities to simultaneously identify early signs of pathology in both organ systems based on the known OSA-driven pathological pathways that result in a disease state in both the cardiovascular and cerebrovascular systems. This narrative review aims to summarize the current link between OSA and neurocognitive disorders, cardio-neural pathophysiology, and the treatment options available for patients with OSA-related neurocognitive disorders.

Sensory Dysfunction, Microbial Infections, and Host Responses in Alzheimer's Disease.

Sensory functions of organs of the head and neck allow humans to interact with the environment and establish social bonds. With aging, smell, taste, vision, and hearing decline. Evidence suggests that accelerated impairment in sensory abilities can reflect a shift from healthy to pathological aging, including the development of Alzheimer's disease (AD) and other neurological disorders. While the drivers of early sensory alteration in AD are not elucidated, insults such as trauma and infections can affect sensory function. Herein, we review the involvement of the major head and neck sensory systems in AD, with emphasis on microbes exploiting sensory pathways to enter the brain (the "gateway" hypothesis) and the potential feedback loop by which sensory function may be impacted by central nervous system infection. We emphasize detection of sensory changes as first-line surveillance in senior adults to identify and remove potential insults, like microbial infections, that could precipitate brain pathology.

Modulating Coagulation via Bioinspired Mesoporous Calcium-Decorated Silica Nanoparticles for Efficient Fibrin Clot Formation.

Blood clotting is vital for preventing bleeding after an injury. Hemostasis is a complex cascade involving numerous plasma proteins. Uncontrolled bleeding leads to mortality. The presence of Ca (calcium) activates and promotes the different phases in the coagulation cascade. Even nonbiological surfaces such as silicates may activate coagulation factor XII (FXII). This causes the clotting of the blood. The exceptional hemostatic ability of the mesoporous calcium-decorated silica nanoparticles (MCSNs) is achieved by stimulating the factors needed to form fibrin mesh, a durable clot, thereby establishing hemostasis. This may be used as a hemostatic agent during an accident surgical procedure and other bleeding-related trauma conditions. This study investigates the mechanistic activation of the coagulation cascade by MCSN through blood coagulation index, clotting time, and coagulation activation studies like PT and aPTT. Our finding demonstrates that MCSN induces platelet adhesion and RBC aggregation and activates thrombin generation through distinct pathways.

Developmental interplay between transcriptional alterations and a targetable cytokine signaling dependency in pediatric ETO2::GLIS2 leukemia.

BACKGROUND: Several fusion oncogenes showing a higher incidence in pediatric acute myeloid leukemia (AML) are associated with heterogeneous megakaryoblastic and other myeloid features. Here we addressed how developmental mechanisms influence human leukemogenesis by ETO2::GLIS2, associated with dismal prognosis. METHODS: We created novel ETO2::GLIS2 models of leukemogenesis through lentiviral transduction and CRISPR-Cas9 gene editing of human fetal and post-natal hematopoietic stem/progenitor cells (HSPCs), performed in-depth characterization of ETO2::GLIS2 transformed cells through multiple omics and compared them to patient samples. This led to a preclinical assay using patient-derived-xenograft models to test a combination of two clinically-relevant molecules. RESULTS: We showed that ETO2::GLIS2 expression in primary human fetal CD34+ hematopoietic cells led to more efficient in vivo leukemia development than expression in post-natal cells. Moreover, cord blood-derived leukemogenesis has a major dependency on the presence of human cytokines, including IL3 and SCF. Single cell transcriptomes revealed that this cytokine environment controlled two ETO2::GLIS2-transformed states that were also observed in primary patient cells. Importantly, this cytokine sensitivity may be therapeutically-exploited as combined MEK and BCL2 inhibition showed higher efficiency than individual molecules to reduce leukemia progression in vivo. CONCLUSIONS: Our study uncovers an interplay between the cytokine milieu and transcriptional programs that extends a developmental window of permissiveness to transformation by the ETO2::GLIS2 AML fusion oncogene, controls the intratumoral cellular heterogeneity, and offers a ground-breaking therapeutical opportunity by a targeted combination strategy.

Predictors of Improvement after Cognitive Training in Mild Cognitive Impairment: Insights from the Cognitive Training and Neuroplasticity in Mild Cognitive Impairment Trial.

OBJECTIVE: Cognitive training may benefit older adults with mild cognitive impairment (MCI), but the prognostic factors are not well-established. METHODS: This study analyzed data from a 78-week trial with 107 participants with MCI, comparing computerized cognitive training (CCT) and computerized crossword puzzle training (CPT). Outcomes were changes in cognitive and functional measures from baseline. Linear mixed-effect models were used to identify prognostic factors for each intervention. RESULTS: Baseline neuropsychological composite z-score was positively associated with cognitive and functional improvements for both interventions in univariable models, retaining significance in the final multivariable model for functional outcome in CPT ( P < 0.001). Apolipoprotein E e4 carriers had worse cognitive ( P = 0.023) and functional ( P = 0.001) outcomes than noncarriers for CPT but not CCT. African Americans showed greater functional improvements than non-African Americans in both CPT ( P = 0.001) and CCT ( P = 0.010). Better baseline odor identification was correlated with cognitive improvements in CPT ( P = 0.006) and functional improvements in CCT ( P < 0.001). CONCLUSION: Baseline cognitive test performance, African American background, and odor identification ability are potential prognostic factors for improved outcomes with cognitive interventions in older adults with MCI. Apolipoprotein E e4 is associated with poor outcomes. Replication of these findings may improve the selection of cognitive interventions for individuals with MCI.

"Visualization matters" - stereoscopic visualization of 3D graphic neuroanatomic models through AnaVu enhances basic recall and radiologic anatomy learning when compared with monoscopy.

BACKGROUND: The authors had previously developed AnaVu, a low-resource 3D visualization tool for stereoscopic/monoscopic projection of 3D models generated from pre-segmented MRI neuroimaging data. However, its utility in neuroanatomical education compared to conventional methods (specifically whether the stereoscopic or monoscopic mode is more effective) is still unclear. METHODS: A three-limb randomized controlled trial was designed. A sample (n = 152) from the 2022 cohort of MBBS students at Government Medical College, Thiruvananthapuram (GMCT), was randomly selected from those who gave informed consent. After a one-hour introductory lecture on brainstem anatomy and a dissection session, students were randomized to three groups (S - Stereo; M - Mono and C - Control). S was given a 20-min demonstration on the brainstem lesson module in AnaVu in stereoscopic mode. M was given the same demonstration, but in monoscopic mode. The C group was taught using white-board drawn diagrams. Pre-intervention and post-intervention tests for four domains (basic recall, analytical, radiological anatomy and diagram-based questions) were conducted before and after the intervention. Cognitive loads were measured using a pre-validated tool. The groups were then swapped -S→ M, M →S and C→S, and they were asked to compare the modes. RESULTS: For basic recall questions, there was a statistically significant increase in the pre/post-intervention score difference of the S group when compared to the M group [p = 0.03; post hoc analysis, Bonferroni corrections applied] and the C group [p = 0.001; ANOVA test; post hoc analysis, Bonferroni corrections applied]. For radiological anatomy questions, the difference was significantly higher for S compared to C [p < 0.001; ANOVA test; post hoc analysis, Bonferroni corrections applied]. Cognitive load scores showed increased mean germane load for S (33.28 ± 5.35) and M (32.80 ± 7.91) compared with C (28.18 ± 8.17). Subjective feedbacks showed general advantage for S and M compared to C. Out of the S and M swap cohorts, 79/102 preferred S, 13/102 preferred M, and 6/102 preferred both. CONCLUSIONS: AnaVu tool seems to be effective for learning neuroanatomy. The specific advantage seen when taught with stereoscopy in basic recall and radiological anatomy learning shows the importance of how visualization mode influences neuroanatomy learning. Since both S and M are preferred in subjective feedbacks, these results have implications in choosing methods (stereoscopic - needs 3D projectors; monoscopic - needs web based or hand-held devices) to scale AnaVu for anatomy teaching in medical colleges in India. Since stereoscopic projection is technically novel and cost considerations are slightly higher compared to monoscopic projection, the specific advantages and disadvantages of each are relevant in the Indian medical education scenario.

Novel measures of cognition and function for the AD spectrum in the Novel Measures for Alzheimer's Disease Prevention Trials (NoMAD) project: Psychometric properties, convergent validation, and contrasts with established measures.

INTRODUCTION: This study derived composite scores for two novel cognitive measures, the No Practice Effect (NPE) battery and the Miami Computerized Functional Skills Assessment and Training system for use in early-stage Alzheimer's disease (AD) clinical trials. Their psychometric properties and associations with AD risk markers were compared to those of well-established measures. METHODS: For 291 older adults with healthy cognition or early mild cognitive impairment, Exploratory factor analyses were used to identify the factor structure of the NPE. Factor and total scores were examined for their psychometric properties and associations with AD risk biomarkers. RESULTS: Composite scores from the novel cognitive and functional measures demonstrated better psychometric properties (distribution and test-retest reliability) and stronger associations with AD-related demographic, genetic, and brain risk markers than well-established measures, DISCUSSION: These novel measures have potential for use as primary cognitive and functional outcomes in early-stage AD clinical trials. HIGHLIGHTS: Well-established cognitive tests may not accurately detect subtle cognitive changes. No Practice Effect (NPE) and Computerized Functional Skills Assessment and Training are novel measures designed to have improved psychometric properties. NPE had Executive Function, Cognitive Control/Speed, and Episodic Memory domains. Novel measures had better psychometric properties compared to established measures. Significant associations with Alzheimer's disease biomarkers were found with novel measures.

T-cell acute lymphoblastic leukemia progression is supported by inflammatory molecules including hepatocyte growth factor.

T-cell acute lymphoblastic leukemia (T-ALL) is a malignant hematological disorder characterized by an increased proliferation of immature T lymphocytes precursors. T-ALL treatment includes chemotherapy with strong side effects, and patients that undergo relapse display poor prognosis. Although cell-intrinsic oncogenic pathways are well-studied, the tumor microenvironment, like inflammatory cellular and molecular components is less explored in T-ALL. We sought to determine the composition of the inflammatory microenvironment induced by T-ALL, and its role in T-ALL progression. We show in two mouse T-ALL cell models that T-ALLs enhance blood neutrophils and resident monocytes, accompanied with a plasmatic acute secretion of inflammatory molecules. Depleting neutrophils using anti-Ly6G treatment or resident monocytes by clodronate liposomes treatment does not modulate plasmatic inflammatory molecule secretion and mice survival. However, inhibiting the secretion of inflammatory molecules by microenvironment with NECA, an agonist of adenosine receptors, diminishes T-ALL progression enhancing mouse survival. We uncovered Hepatocyte Growth Factor (HGF), T-ALL-driven and the most decreased molecule with NECA, as a potential therapeutic target in T-ALL. Altogether, we identified a signature of inflammatory molecules that can potentially be involved in T-ALL evolution and uncovered HGF/cMET pathway as important to target for limiting T-ALL progression.

COVID-19 olfactory dysfunction: associations between coping, quality of life, and mental health.

BACKGROUND: Persistent olfactory dysfunction (OD) is a common symptom following SARS-CoV-2 infection that can greatly impact quality of life (QoL). Because coping strategies have been shown to moderate the effect of disease symptoms on functional and affective outcomes, this study aims to determine whether specific coping strategies are associated with and moderate QoL outcomes. METHODOLOGY: Participants with prior SARS-CoV-2 infection underwent psychophysical olfactory testing with Sniffin’ Sticks and completed questionnaires to elicit subjective olfactory function, coping strategies, olfactory-specific QoL, general QoL, and mental health. RESULTS: There were 93 participants included in the study. Olfactory specific QoL scores were significantly worse among individuals with subjective and psychophysically measured OD compared to those with subjective and psychophysically confirmed normosmia. Olfactory-specific QoL, general QoL, and anxiety symptom scores were positively correlated with avoidant and disengagement coping among individuals with subjective and psychophysically measured OD. Depression symptom scores were positively correlated with avoidant and disengagement coping and negatively correlated with approach and engagement coping. There were no significant moderating effects on the association between olfactory performance and QoL or mental health screening assessment. CONCLUSIONS: Approach and engagement coping mechanisms are associated with improved depression, whereas avoidant and disengagement coping tracks with worse QoL and mental health screening assessment, offering an opportunity to counsel patients accordingly.

Oxytocin receptor function regulates neural signatures of pair bonding and fidelity in the nucleus accumbens.

The formation of enduring relationships dramatically influences future behavior, promoting affiliation between familiar individuals. How such attachments are encoded to elicit and reinforce specific social behaviors in distinct ethological contexts remains unknown. Signaling via the oxytocin receptor (Oxtr) in the nucleus accumbens (NAc) facilitates social reward as well as pair bond formation between mates in socially monogamous prairie voles 1-9 . How Oxtr function influences activity in the NAc during pair bonding to promote affiliative behavior with partners and rejection of other potential mates has not been determined. Using longitudinal in vivo fiber photometry in wild-type prairie voles and those lacking Oxtr, we demonstrate that Oxtr function sex-specifically regulates pair bonding behaviors and associated activity in the NAc. Oxtr function influences prosocial behavior in females in a state-dependent manner. Females lacking Oxtr demonstrate reduced prosocial behaviors and lower activity in the NAc during initial chemosensory investigation of novel males. Upon pair bonding, affiliative behavior with partners and neural activity in the NAc during these interactions increase, but these changes do not require Oxtr function. Conversely, males lacking Oxtr display increased prosocial investigation of novel females. Using the altered patterns of behavior and activity in the NAc of males lacking Oxtr during their first interactions with a female, we can predict their future preference for a partner or stranger days later. These results demonstrate that Oxtr function sex-specifically influences the early development of pair bonds by modulating prosociality and the neural processing of sensory cues and social interactions with novel individuals, unmasking underlying sex differences in the neural pathways regulating the formation of long-term relationships.

Characterizing Neighborhood Vulnerabilities in Mild Cognitive Impairment using the Environmental Justice Index.

Background: There is a need for integration and comprehensive characterization of environmental determinants of Alzheimer's disease. The Environmental Justice Index (EJI) is a new measure that consolidates multiple environmental health hazards. Objective: This analysis aims to explore how environmental vulnerabilities vary by race/ethnicity and whether they predict cognitive outcomes in a clinical trial of mild cognitive impairment (MCI). Methods: We used data from a clinical trial of 107 MCI participants (28% minorities). Using the EJI, we extracted 40 measures of neighborhood environmental and social vulnerability including air and water pollution, access to recreational spaces, exposure to coal and lead mines, and area poverty. We also examined the relationship of the EJI to the Area Deprivation Index (ADI). Data was analyzed using regressions, correlations, and t-tests. Results: Environmental Burden Rank (EBR) across the sample (0.53±0.32) was near the 50th percentile nationally. When divided by race/ethnicity, environmental (p = 0.025) and social (p < 0.0001) vulnerabilities were significantly elevated for minorities, specifically for exposure to ozone, diesel particulate matter, carcinogenic air toxins, and proximity to treatment storage and disposal sites. ADI state decile was not correlated with the EBR. Neither EBR nor ADI were a significant predictor of cognitive decline. Conclusions: To our knowledge, this is the first study to link the EJI to an MCI trial. Despite limitations of a relatively small sample size, the study illustrates the potential of the EJI to provide deeper phenotyping of the exposome and diversity in clinical trial subjects.

Recovery rates of persistent post-COVID-19 olfactory dysfunction using psychophysical assessment: A longitudinal cohort study.

Objectives: Persistent olfactory dysfunction (OD) following loss of smell associated with SARS-CoV-2 infection is a major feature of long COVID. Perspectives on the prevalence of persistent OD predominantly rely on self-reported olfactory function. Few studies have tracked longitudinal rates of recovery using psychophysical assessment among patients presenting for evaluation of persistent OD beyond a window of acute recovery. Data anchored in standardized testing methods are needed to counsel patients who fail to acutely regain their sense of smell. This study aims to quantify the degree of persistent OD in post-COVID-19 patients who experience subjective and psychophysical OD. Methods: We grouped participants presenting for OD evaluation into cohorts based on both subjective and psychophysical olfactory status at a baseline assessment and assessed their olfactory abilities with a visual analogue scale and the Sniffin' Sticks extended test at baseline and 1-year time points. Participants had confirmed a history of COVID-19 by lab evaluation or clinical diagnosis if lab evaluation was not available. Results: Baseline olfactory evaluation was completed by 122 participants, 53 of whom completed the 1-year follow-up assessment. Among participants presenting with perceived OD, 74.5% had confirmed psychophysical OD at baseline, with 55.1% at 1-year follow-up. Participants had reliable trends in self-rated versus psychophysically tested olfactory function at both time points. The total threshold, discrimination, and identification (TDI) score improved by +3.25 points in the cohort with psychophysical OD (p = 0.0005), with this improvement largely attributable to an increase in median threshold scores (+2.75 points; p = 0.0004). Conclusions: OD persists in a significant number of patients who fail to acutely recovery their sense of smell after COVID-19, with many demonstrating lingering deficits at 1-year. Improvements in threshold, but not discrimination or identification, most significantly mediate improvement of total TDI score at follow-up.

Diagnostic value and safety of medical thoracoscopy in undiagnosed pleural effusions-a prospective observational cohort study.

Background: With the need for "actionable histology" in the current era of targeted cancer treatment, and the increasing practice of upfront thoracoscopy (without a prior diagnostic thoracentesis) or a "biopsy first" approach in suspected malignant pleural effusions (MPEs), we sought to prospectively evaluate the diagnostic accuracy, including full molecular profiling of cancer, and safety of medical thoracoscopy (MT) at a tertiary referral hospital. Methods: Patients with MT performed for an undiagnosed pleural effusion between January 2020 and December 2022 were included in this observational cohort study. All procedures were performed with a semirigid thoracoscope under conscious sedation. Clinical outcomes and adverse events were recorded prospectively. Results: We evaluated 141 patients, with a mean age of 67±12 years. Talc poudrage was performed in 67 (47.5%) patients with a median of 2 [interquartile range (IQR), 1-4] hospitalisation days after MT. Upfront thoracoscopy was performed in approximately half (55.3%) of patients. The overall diagnostic accuracy of MT was 95.7% in our cohort. A final diagnosis of cancer was made in 116 (82.3%) patients, with lung (67.2%) and breast cancer (8.6%) the most common. The diagnostic sensitivity of MT for malignancy was 94.8%, and molecular profiling of relevant cancer types for oncogenic mutations was achieved in all patients with malignancy seen on histopathology. The most common non-malignant diagnosis was tuberculous pleuritis in 14 patients (9.9%). Major complications occurred in 3 (2.1%) patients. Two patients had re-expansion pulmonary edema that resolved with low flow oxygen supplementation in the general ward, and one patient required intensive care unit admission for cardiac tamponade from a malignant pericardial effusion. There were no cases of mortality, bleeding complications or persistent air leaks. Conclusions: MT is a well-tolerated and effective option for the evaluation of undiagnosed pleural effusions. With expanding utility and expertise with MT and other pleural interventions, the challenge for respiratory physicians is integrating these into expeditious diagnostic and effective therapeutic pathways, individualised to patients' needs.

Enhanced coagulation cascade activation and styptic effects of Zn@SiO2 nanocomposite.

Humans often have bleeding, which exerts substantial selective pressure on the coagulation system to optimize hemostasis in a variety of situations. Uncontrolled hemorrhage due to severe trauma leads to morbidity and mortality. Although nonbiological surfaces such as silicates can activate coagulation factor XII (FXII), the presence of Zn (Zinc) in the material stimulates and activates the various steps in the coagulation cascade. This results in blood clotting. The Zn@SiO2 nanocomposite has an excellent hemostatic property that establishes hemostasis by activating the factors responsible for the formation of a stable clot called fibrin mesh. This can be used as a hemostatic agent during surgeries and in any other trauma condition related to bleeding. Zn@SiO2 was synthesized and characterized with XRD, FTIR and HRTEM. It is analyzed for its RBC (Red Blood Corpuscles) aggregation and Platelet adhesion ability, fibrin formation, thrombus formation and prothrombin time (PT), Activated Partial Thromboplastin Time (aPTT), D-dimer for its ability to activate the coagulation cascade to achieve stable clotting.