We report on femtosecond laser ablation experiments on percolating gold layers deposited on a glass substrate. In our experiments, we measure changes in optical transmission and reflection induced by ...single, high-intensity infrared laser pulses as a function of the time delay between the pump and the probe. For the highest pump intensities we find that on a time scale of about 150 ps after excitation, the transmission and reflection approach values close to the substrate values. We attribute this rapid ablation to vaporization of the entire layer when the injected energy exceeds the cohesive energy of the material. This vaporization results in the rapid transformation of the gold layer into a sufficiently dilute mist of atoms and nano-particles which renders the material almost optically transparent to the probe pulse. SEM images of the surfaces show how the morphology of the films changes at relatively low excitation intensities and show the complete removal of the gold at high intensities. We find that the ablation threshold for percolating Au on glass is 2.3 × 10
W/cm
, which is two orders of magnitude lower than the damage threshold for continuous gold layers as reported in the literature.
Observational studies have shown an association between obesity and venous thromboembolism (VTE) but it is not known if observed associations are causal, due to reverse causation or confounding bias. ...We conducted a Mendelian Randomization study of body mass index (BMI) and VTE. We identified 95 single nucleotide polymorphisms (SNPs) that have been previously associated with BMI and assessed the association between genetically predicted high BMI and VTE leveraging data from a previously conducted GWAS within the INVENT consortium comprising a total of 7507 VTE cases and 52,632 controls of European ancestry. Five BMI SNPs were associated with VTE at
P
< 0.05, with the strongest association seen for the
FTO
SNP rs1558902 (OR 1.07, 95% CI 1.02–1.12,
P
= 0.005). In addition, we observed a significant association between genetically predicted BMI and VTE (OR = 1.59, 95% CI 1.30–1.93 per standard deviation increase in BMI,
P
= 5.8 × 10
−6
). Our study provides evidence for a causal relationship between high BMI and risk of VTE. Reducing obesity levels will likely result in lower incidence in VTE.
Essentials
Genetic variation may provide valuable insight into the role of the contact system in thrombosis.
Explored associations of genetic variants with activity, antigen, and disease in RATIO ...study.
Two novel loci were identified: KLKB1 rs4253243 for prekallikrein; KNG1 rs5029980 for HMWK levels.
Contact system variants and haplotypes were not associated with myocardial infarction or stroke.
Summary
Background
The complex, interdependent contact activation system has been implicated in thrombotic disease, although few genetic determinants of levels of proteins from this system are known.
Objectives
Our primary aim was to study the influence of common F11, F12, KLKB1, and KNG1 variants on factor (F) XI activity and FXI, FXII, prekallikrein (PK) and high‐molecular‐weight kininogen (HMWK) antigen levels, as well as the risk of myocardial infarction and ischemic stroke.
Patients/methods
We analyzed samples from all 630 healthy participants, 182 ischemic stroke patients and 216 myocardial infarction patients in the RATIO case–control study of women aged < 50 years. Forty‐three tagging single nucleotide variants (SNVs) were genotyped to represent common genetic variation in the contact system genes. Antigen and activity levels were measured with sandwich‐ELISA‐based and one‐stage clotting assays. We performed single variant, age‐adjusted, linear regression analyses per trait and disease phenotype, assuming additive inheritance and determined conditionally independent associations. Haplotypes based on the lead SNV and all conditionally independent SNVs were tested for association with traits and disease.
Results
We identified two novel associations of KLKB1 SNV rs4253243 with PK antigen (βconditional = −12.38; 95% CI, −20.07 to −4.69) and KNG1 SNV rs5029980 with HMWK antigen (βconditional = 5.86; 95% CI, 2.40–9.32) and replicated previously reported associations in a single study. Further analyses probed whether the observed associations were indicative of linkage, pleiotropic effects or mediation. No individual SNVs or haplotypes were associated with the disease outcomes.
Conclusion
This study adds to current knowledge of how genetic variation influences contact system protein levels and clarifies interdependencies.
There are no risk models available yet that accurately predict a person's risk for developing venous thrombosis. Our aim was therefore to explore whether inclusion of established ...thrombosis-associated single nucleotide polymorphisms (SNPs) in a venous thrombosis risk model improves the risk prediction. We calculated genetic risk scores by counting risk-increasing alleles from 31 venous thrombosis-associated SNPs for subjects of a large case-control study, including 2712 patients and 4634 controls (Multiple Environmental and Genetic Assessment). Genetic risk scores based on all 31 SNPs or on the 5 most strongly associated SNPs performed similarly (areas under receiver-operating characteristic curves AUCs of 0.70 and 0.69, respectively). For the 5-SNP risk score, the odds ratios for venous thrombosis ranged from 0.37 (95% confidence interval CI, 0.25-0.53) for persons with 0 risk alleles to 7.48 (95% CI, 4.49-12.46) for persons with more than or equal to 6 risk alleles. The AUC of a risk model based on known nongenetic risk factors was 0.77 (95% CI, 0.76-0.78). Combining the nongenetic and genetic risk models improved the AUC to 0.82 (95% CI, 0.81-0.83), indicating good diagnostic accuracy. To become clinically useful, subgroups of high-risk persons must be identified in whom genetic profiling will also be cost-effective.
Reading difficulties are amongst the most commonly reported problems in individuals with homonymous visual field defects (HVFDs). To be able to provide guidance for healthcare professionals ...considering offering reading training, researchers in this field and interested individuals with HVFDs, this systematic review aims to (1) provide an overview of the contextual and intervention characteristics of all published HVFD interventions and (2) generate insights into the different reading outcome measures that these studies adopted. A search on PsycINFO, MEDLINE and Web of Science was conducted up to February 2, 2023. All intervention studies for HVFD in which reading was measured were included. Data was collected about the intervention type, session duration, number of sessions, the intensity, duration, circumstance of the interventions, country in which the intervention was studied and reading measures. Sixty records are included, describing 70 interventions in total of which 21 are specifically reading interventions. Overall, adjusted saccadic behaviour interventions occur most in the literature. A wide range within all intervention characteristics was observed. Forty-nine records reported task-performance reading measures, and 33 records reported self-reported reading measures. The majority of task-performance measures are based on self-developed paragraph reading tasks with a time-based outcome measure (e.g. words per minute). Future research could benefit from making use of validated reading tests, approaching the measurement of reading mixed-methods and providing participants the possibility to supply outcomes relevant to them.
Remote pulse oximetry in visible light (VIS) is a relevant application of photoplethysmography (PPG). However, wavelengths penetrate at different depths and VIS-based pulse oximetry may not guarantee ...robustness to physiological variations of the skin properties. This paper shows how a simple manoeuver like a posture change can hamper the accuracy of a method relying on red and the less penetrating green wavelengths.
Stationary subjects were measured under normoxic conditions while sitting and in the supine position. For each recording, we extracted remote PPG signals from forehead video recordings of 31 healthy adults at the red and green camera channels. The resulting normalized PPG-amplitudes, and its ratio, red-over-green (RoG), were compared between postures. The observed RoG changes were translated into estimates for arterial blood oxygen saturation (SpO
, %) errors by means of Monte Carlo simulations of the skin tissue. Simulations were also used to compare the calibratability errors of SpO
in VIS against the conventional red-IR wavelengths.
RoG differs significantly between postures (RoG: sitting, 0.100 Formula: see text 0.025; supine, 0.123 Formula: see text 0.033), mediated by PPG-amplitude changes in green. The posture interference in RoG may be mitigated by an offset correction. Without this correction, we estimated that the observed change in RoG causes SpO
errors >Formula: see text. Analogous simulations involving red-IR wavelengths indicate SpO
errors <Formula: see text.
Our results show that the calibrations for remote pulse oximetry in VIS require the specification of a fixed measurement position. Future work could be aimed at controlling for posture in measurements.
The authors describe 12 pregnancies in women with epilepsy using lamotrigine (LTG) monotherapy. A seizure increase in nine pregnancies was probably related to a gradual decline of LTG level-to-dose ...ratio to 40% of baseline. After delivery, LTG kinetics returned swiftly to baseline, causing toxic side effects in some women. Frequent LTG level monitoring and appropriate dose adjustments are advised in the period before and during pregnancy and after delivery, especially in women on LTG monotherapy.
As the transcriptional coactivator CITED2 (CBP/p300-interacting-transactivator-with-an ED-rich-tail 2) can be overexpressed in acute myeloid leukemia (AML) cells, we analyzed the consequences of high ...CITED2 expression in normal and AML cells. CITED2 overexpression in normal CD34(+) cells resulted in enhanced hematopoietic stem and progenitor cell (HSPC) output in vitro, as well as in better hematopoietic stem cell (HSC) engraftability in NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice. This was because of an enhanced quiescence and maintenance of CD34(+)CD38(-) HSCs, due in part to an increased expression of the cyclin-dependent kinase inhibitor CDKN1A. We demonstrated that PU.1 is a critical regulator of CITED2, as PU.1 repressed CITED2 expression in a DNA methyltransferase 3A/B (DNMT3A/B)-dependent manner in normal CD34(+) cells. CD34(+) cells from a subset of AML patients displayed higher expression levels of CITED2 as compared with normal CD34(+) HSPCs, and knockdown of CITED2 in AML CD34(+) cells led to a loss of long-term expansion, both in vitro and in vivo. The higher CITED2 expression resulted from reduced PU.1 activity and/or dysfunction of mutated DNMT3A/B. Collectively, our data demonstrate that increased CITED2 expression results in better HSC maintenance. In concert with low PU.1 levels, this could result in a perturbed myeloid differentiation program that contributes to leukemia maintenance.
Essentials
Deep vein thrombosis (DVT) has a large unknown genetic component.
We sequenced coding areas of 734 hemostasis‐related genes in 899 DVT patients and 599 controls.
Variants in F5, FGA‐FGG, ...CYP4V2‐KLKB1‐F11, and ABO were associated with DVT risk.
Associations in
KLKB1 and F5 suggest a more complex genetic architecture than previously thought.
Summary
Background
Although several genetic risk factors for deep vein thrombosis (DVT) are known, almost all related to hemostasis, a large genetic component remains unexplained.
Objectives
To identify novel genetic determinants by using targeted DNA sequencing.
Patients/Methods
We included 899 DVT patients and 599 controls from three case–control studies (DVT‐Milan, Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis MEGA, and the Thrombophilia, Hypercoagulability and Environmental Risks in Venous Thromboembolism THE‐VTE study) for sequencing of the coding regions of 734 genes involved in hemostasis or related pathways. We performed single‐variant association tests for common variants (minor allele frequency MAF ≥ 1%) and gene‐based tests for rare variants (MAF ≤ 1%), accounting for multiple testing by use of the false discovery rate (FDR).
Results
Sixty‐two of 3617 common variants were associated with DVT risk (FDR < 0.10). Most of these mapped to F5,ABO,FGA–FGG, and CYP4V2–KLKB1–F11. The lead variant at F5 was rs6672595 (odds ratio OR 1.58, 95% confidence interval CI 1.29–1.92), in moderate linkage with the known variant rs4524. Reciprocal conditional analyses suggested that intronic variation might drive this association. We also observed a secondary association at the F11 region: missense KLKB1 variant rs3733402 remained associated conditional on known variants rs2039614 and rs2289252 (OR 1.36, 95% CI 1.10–1.69). Two novel variant associations were observed, in CBS and MASP1, but these were not replicated in the meta‐analysis data from the International Network against Thrombosis (INVENT) consortium. There was no support for a burden of rare variants contributing to DVT risk (FDR > 0.2).
Conclusions
We confirmed associations between DVT and common variants in F5,ABO,FGA–FGG, and CYP4V2–KLKB1–F11, and observed secondary signals in F5 and CYP4V2–KLKB1–F11 that warrant replication and fine‐mapping in larger studies.
Summary
Malaria is a worldwide health problem with 225 million infections each year. A fast and easy‐to‐use method, with high performance is required to differentiate malaria from non‐malarial ...fevers. Manual examination of blood smears is currently the gold standard, but it is time‐consuming, labour‐intensive, requires skilled microscopists and the sensitivity of the method depends heavily on the skills of the microscopist.
We propose an easy‐to‐use, quantitative cartridge‐scanner system for vision‐based malaria diagnosis, focusing on low malaria parasite densities. We have used special finger‐prick cartridges filled with acridine orange to obtain a thin blood film and a dedicated scanner to image the cartridge. Using supervised learning, we have built a Plasmodium falciparum detector. A two‐step approach was used to first segment potentially interesting areas, which are then analysed in more detail. The performance of the detector was validated using 5 420 manually annotated parasite images from malaria parasite culture in medium, as well as using 40 cartridges of 11 780 images containing healthy blood.
From finger prick to result, the prototype cartridge‐scanner system gave a quantitative diagnosis in 16 min, of which only 1 min required manual interaction of basic operations. It does not require a wet lab or a skilled operator and provides parasite images for manual review and quality control. In healthy samples, the image analysis part of the system achieved an overall specificity of 99.999978% at the level of (infected) red blood cells, resulting in at most seven false positives per microlitre. Furthermore, the system showed a sensitivity of 75% at the cell level, enabling the detection of low parasite densities in a fast and easy‐to‐use manner. A field trial in Chittagong (Bangladesh) indicated that future work should primarily focus on improving the filling process of the cartridge and the focus control part of the scanner.
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