The bleeding risks for nonsyndromic platelet function disorders (PFDs) that impair aggregation responses and/or cause dense granule deficiency (DGD) are uncertain.
Our goal was to quantify bleeding ...risks for a cohort of consecutive cases with uncharacterized PFD.
Sequential cases with uncharacterized PFDs that had reduced maximal aggregation (MA) with multiple agonists and/or nonsyndromic DGD were invited to participate along with additional family members to reduce bias. Index cases were further evaluated by exome sequencing, with analysis of RUNX1‐dependent genes for cases with RUNX1 sequence variants. Bleeding assessment tools were used to estimate bleeding scores, with bleeding risks estimated as odds ratios (ORs) relative to general population controls. Relationships between symptoms and laboratory findings were also explored.
Participants with uncharacterized PFD (n = 37; 23 index cases) had impaired aggregation function (70%), nonsyndromic DGD (19%) or both (11%), unlike unaffected relatives. Probable pathogenic RUNX1 variants were found in 2 (9%) index cases/families, whereas others had PFD of unknown cause. Participants with PFD had increased bleeding scores compared to unaffected family members and general population controls, and increased risks for mucocutaneous (OR, 4‐207) and challenge‐related bleeding (OR, 12‐43), and for receiving transfusions for bleeding (OR, 100). Reduced MA with collagen was associated with wound healing problems and bruising, and more severe DGD was associated with surgical bleeding (P < .04).
PFDs that impair MA and/or cause nonsyndromic DGD have significantly increased bleeding risks, and some symptoms are more common in those with more severe DGD or impaired collagen aggregation.
Long-distance pipelines are one of the primary means of oil and gas transportation. During the construction process, long-distance pipelines are inevitably buried across geohazard zones, which ...potentially generate permanent ground displacements. These ground displacements can potentially induce excessive strains in the pipe posing a great threat to the pipe’s safety and integrity. In this study, a new numerical methodology for the response analysis of pipes subjected to ground displacements is proposed based on the finite difference method. Simulating the pipeline as a large deformation Euler Bernoulli beam, the finite difference method is used to solve the two interacting nonlinear differential equations of equilibrium in the longitudinal and lateral directions considering the nonlinear pipe-soil interaction induced by the ground displacement. Implemented using the nonlinear equation solver of FindRoot by Mathematica for solving nonlinear equations, the longitudinal strain along the pipeline can be subsequently derived, and the tensile and compressive strain demands can be therefore determined for engineering reference. Finally, the applicability of this method is validated based on two hypothetical study cases involving symmetric and non-symmetric soil resistance on the lateral direction of the pipe. Comparing the results with the finite element analysis solver Abaqus, we demonstrate that this present methodology has excellent predictive capabilities. Our study is carried out for elastic response calculation, but the proposed method shows a great promise for further development involving material nonlinearity, which is appropriate for the preliminary safety evaluation for the design of new pipelines or for risk prescreening of existing pipelines.
Platelet function disorders represent a heterogeneous group of bleeding disorders with diverse molecular causes that are frequently associated with platelet dense granule deficiency and/or impaired ...aggregation responses. With the exception of Quebec platelet disorder (QPD), bleeding risks for common platelet disorders have not been estimated. This led us to study a Canadian cohort with uncharacterized platelet function disorders and confirmed abnormalities in validated assays for platelet dense granule deficiency and/or light transmission aggregometry (reduced aggregation with ≥2 agonists). Subjects were assessed using: (i) the International Society for Thrombosis and Haemostasis bleeding assessment tool (ISTH-BAT) to determine scores and categorize symptom severity, and (ii) CHAT-P, a clinical history assessment tool for assessment of platelet disorders that included questions about general health and bleeding symptoms/problems and questions previously used to assess bleeding risks for QPD. CHAT-P was completed by subjects (or parent in the case of young children) before review by a hematologist. Participants included: 29 individuals with confirmed platelet function disorders of unknown cause (from 7 families, 10 "sporadic" cases), 12 unaffected relatives and 60 general population controls. A one-way ANOVA was used to compare the overall ISTH-BAT scores between the affected individuals, unaffected relatives and healthy controls. Bleeding risks were estimated as odds ratio (OR) with 95% confidence intervals (CI) using CHAT-P data for general population controls as the comparison group. The total number of affected subjects reporting a bleeding problem/symptom from the group of affected individuals was added up and compared with the corresponding numbers of responses for general population controls and unaffected relatives using ANOVA. Summative bleeding scores for CHAT-P items with OR>1 were used to compare the number and range of abnormal bleeding symptoms experienced by subjects. Individuals with confirmed platelet abnormalities had higher ISTH-BAT scores (median: 9, range: 0-18) than unaffected family members (median: 0, range: 0-1) and general population controls (median: 0, range: 0-6) (p < 0.01), and their most severe symptom scores were for: epistaxis, cutaneous bleeding, menorrhagia, bleeding from dental extractions, surgery and a subdural hematoma at birth. Affected individuals had higher risks for bleeding (OR, 95% CI, p value) including: bleeding from minor cuts/wounds lasting >1 hour (56, 3.1-1000, p<0.01); abnormal bruising (15-65, 1.8-140 to 3.7-1200, p<0.01); prolonged nosebleeds (23, 5.9-92, p<0.01) and nosebleeds requiring medical attention (40, 1.5-520, p<0.01), packing (33, 1.8-620, p<0.01) or cautery (27, 1.5-510, p<0.01); wound healing problems (13, 3.4-53, p<0.01); excessive bleeding from injuries/trauma (9.5, 1-87, p=0.03), oral/dental challenges (44, 5.3-370, p<0.01) and surgery (17, 4.1-68, p<0.01). Affected females reported: bleeding interfering with their sex life (6.5, 1.1-38, p=0.04); menses >7 days (11, 2.5-49, p<0.01); flooding/gushing accidents (3.8, 1.2-12, p=0.04 ) and/or clots with menses (13, 2.6-63, p<0.01); menses requiring treatment (7.8, 2.1-29, p<0.01); and excessive bleeding during childbirth (17, 2.7-105, p<0.01), sometimes requiring surgical intervention (41, 2-810, p<0.01). Affected individuals reported more of these bleeding symptoms (median: 15, range: 0-24) than unaffected family members (median: 2, range: 0-6; p<0.01) and general population controls (median: 1, range: 0-14, p<0.01), although there was overlap. Our study illustrates that uncharacterized platelet function disorders are associated with significantly increased bleeding risks and mild rather than severe bleeding problems. It will be important to translate our study findings for patients and healthcare providers to promote evidence-based care of individuals with confirmed dense granule deficiency and/or impaired aggregation responses, which are common amongst individuals tested for bleeding problems.
No relevant conflicts of interest to declare.
Irradiation of fibular grafts for jaw reconstruction following mandibulectomy can be associated with increased graft failure and implant instability. The objective of this study is to investigate the ...effect of isolated irradiation on the biomechanical properties of ex-vivo porcine fibula grafts. It was hypothesized that the isolated irradiation (without biological response) will not significantly influence the biomechanical properties of the fibular grafts.
Forty porcine fibular grafts (n = 20 irradiated and n = 20 nonirradiated) were obtained. The irradiated group was subjected to a single dose of 60 Gy of irradiation with cesium 137. Both groups underwent 3-point bending tests with cyclic loading for 1500 cycles (50 to 500 N at 2 Hz) followed by push to failure. Rate of damage (mm/s), stiffness (N/mm), modulus of elasticity (MPa), maximum load (N), maximum displacement (mm), and maximum stress (MPa) were compared between the 2 groups using independent t tests (P < .05).
No significant differences were found between the irradiated and nonirradiated groups for any of the biomechanical parameters (all P values > 0.05).
The results of this study support our hypothesis that even high levels of isolated irradiation do not significantly affect the biomechanical properties of fibular bone grafts. This work allows us to exclude acute structural changes in the bone due to irradiation as a possible factor leading to bone/implant instability following jaw reconstruction with fibular grafts. Further studies need to be conducted to better understand the range of factors that may lead to implant instability, including the biological response after radiation therapy.
Background:
The all-inside anterior cruciate ligament reconstruction (ACLR) procedure uses a single hamstring tendon folded twice and secured to itself to form a 4-stranded graft. There are several ...possible configurations for preparing the graft.
Purpose:
To investigate the biomechanical properties of a new graft preparation technique in comparison with 2 commonly used configurations.
Study Design:
Controlled laboratory study.
Methods:
Five porcine flexor tendons were prepared into the test graft configuration: side-to-side fixation with a backup fixation at the button loop (graft M). The test configuration was compared with the results of a previous study that included grafts with simple interrupted sutures (graft A; n = 5) and end-to-end fixation (graft C; n = 5). All grafts were subjected to the same mechanical testing protocol to determine the mean failure load, stiffness, rate of elongation, and total elongation during both cyclic loading and pull to failure. Differences between groups were evaluated.
Results:
Graft A had a significantly lower failure load (637 ± 99 N) compared with graft M (883 ± 66 N; P = .002) and graft C (846 ± 26 N; P = .002). Graft A also had significantly lower stiffness (166 ± 12 N/mm) compared with graft M (215 ± 8 N/mm; P < .001) and graft C (212 ± 11 N/mm; P < .001). Graft C had a significantly lower elongation during cyclic loading (3.42 ± 0.24 mm) compared with graft M (4.37 ± 0.74 mm; P = .026) and graft A (4.90 ± 0.88 mm; P = .006). The unsecured fixation was the weakest graft, with the lowest failure load and stiffness. The new side-to-side configuration and end-to-end configuration were equally strong.
Conclusion:
The new side-to-side configuration was not biomechanically superior to the end-to-end configuration; however, they were both stronger than unsecured fixation.
Clinical Relevance:
As the all-inside ACLR is gaining popularity, this study provides surgeons with a new method of preparing grafts and evaluates the method with respect to currently used configurations.
Leishmania species of the Viannia subgenus are responsible for most cases of New World tegumentary leishmaniasis. However, little is known about the vectors involved in disease transmission in the ...Amazon regions of Peru. We used a novel real-time polymerase chain reaction (PCR) to assess Leishmania infections in phlebotomines collected in rural areas of Madre de Dios, Peru. A total of 1,299 non-blood fed female sand flies from 33 species were captured by using miniature CDC light traps. Lutzomyia auraensis was the most abundant species (63%) in this area. Seven of 164 pools were positive by PCR for Leishmania by kinetoplast DNA. The real-time PCR identified four Lu. auraensis pools as positive for L. (Viannia) lainsoni and L. (V.) braziliensis. The minimum infection prevalence for Lu. auraensis was estimated to be 0.6% (95% confidence interval = 0.20-1.42%). Further studies are needed to assess the importance of Lu. auraensis in the transmission of New World tegumentary leishmaniasis in hyperendemic areas of Peru.
The oxygen isotope composition (δ18O) of tree‐ring cellulose is used to evaluate tree physiological responses to climate, but their interpretation is still limited due to the complexity of the ...isotope fractionation pathways.We assessed the relative contribution of seasonal needle and xylem water δ18O variations to the intra‐annual tree‐ring cellulose δ18O signature of larch trees at two sites with contrasting soil water availability in the Swiss Alps. We combined biweekly δ18O measurements of soil water, needle water, and twig xylem water with intra‐annual δ18O measurements of tree‐ring cellulose, xylogenesis analysis, and mechanistic and structural equation modeling.Intra‐annual cellulose δ18O values resembled source water δ18O mean levels better than needle water δ18O. Large parts of the rings were formed under high proportional exchange with unenriched xylem water (pex). Maximum pex values were achieved in August and imprinted on sections at 50–75% of the ring. High pex values were associated with periods of high atmospheric evaporative demand (VPD). While VPD governed needle water δ18O variability, we estimated a limited Péclet effect at both sites.Due to a variable pex, source water has a strong influence over large parts of the intra‐annual tree‐ring cellulose δ18O variations, potentially masking signals coming from needle‐level processes.
In South America, various species of Leishmania are endemic and cause New World tegumentary leishmaniasis (NWTL). The correct identification of these species is critical for adequate clinical ...management and surveillance activities. We developed a real-time polymerase chain reaction (PCR) assay and evaluated its diagnostic performance using 64 archived parasite isolates and 192 prospectively identified samples collected from individuals with suspected leishmaniasis enrolled at two reference clinics in Lima, Peru. The real-time PCR assay was able to detect a single parasite and provided unambiguous melting peaks for five Leishmania species of the Viannia subgenus that are highly prevalent in South America: L. (V.) braziliensis, L. (V.) panamensis, L. (V.) guyanensis, L. (V.) peruviana and L. (V.) lainsoni. Using kinetoplastid DNA-based PCR as a gold standard, the real-time PCR had sensitivity and specificity values of 92% and 77%, respectively, which were significantly higher than those of conventional tests such as microscopy, culture and the leishmanin skin test (LST). In addition, the real-time PCR identified 147 different clinical samples at the species level, providing an overall agreement of 100% when compared to multilocus sequence typing (MLST) data performed on a subset of these samples. Furthermore, the real-time PCR was three times faster and five times less expensive when compared to PCR - MLST for species identification from clinical specimens. In summary, this new assay represents a cost-effective and reliable alternative for the identification of the main species causing NWTL in South America.
Summary
Generalised dose–response curves are essential to understand how plants acclimate to atmospheric CO2. We carried out a meta‐analysis of 630 experiments in which C3 plants were experimentally ...grown at different CO2 under relatively benign conditions, and derived dose–response curves for 85 phenotypic traits. These curves were characterised by form, plasticity, consistency and reliability. Considered over a range of 200–1200 µmol mol−1 CO2, some traits more than doubled (e.g. area‐based photosynthesis; intrinsic water‐use efficiency), whereas others more than halved (area‐based transpiration). At current atmospheric CO2, 64% of the total stimulation in biomass over the 200–1200 µmol mol−1 range has already been realised. We also mapped the trait responses of plants to CO2 against those we have quantified before for light intensity. For most traits, CO2 and light responses were of similar direction. However, some traits (such as reproductive effort) only responded to light, others (such as plant height) only to CO2, and some traits (such as area‐based transpiration) responded in opposite directions. This synthesis provides a comprehensive picture of plant responses to CO2 at different integration levels and offers the quantitative dose–response curves that can be used to improve global change simulation models.
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