Search for the Standard Model Higgs Boson with the OPAL Detector at LEP

This paper summarises the search for the Standard Model Higgs boson in e+e- collisions at centre-of-mass energies up to 209 GeV performed by the OPAL Collaboration at LEP. The consistency of the data with the background hypothesis and various Higgs boson mass hypotheses is examined. No indication of a signal is found in the data and a lower bound of 112.7GeV/C^2 is obtained on the mass of the Standard Model Higgs boson at the 95% CL.Comment: 51 pages, 21 figure

Exploring the limitations of blood pressure estimation using the photoplethysmography signal

Hypertension, a leading contributor to cardiovascular morbidity, underscores the need for accurate and continuous blood pressure (BP) monitoring. Photoplethysmography (PPG) presents a promising approach to this end. However, the precision of BP estimates derived from PPG signals has been the subject of ongoing debate, necessitating a comprehensive evaluation of their effectiveness and constraints. We developed a calibration-based Siamese ResNet model for BP estimation, using a signal input paired with a reference BP reading. We compared the use of normalized PPG (N-PPG) against the normalized Invasive Arterial Blood Pressure (N-IABP) signals as input. The N-IABP signals do not directly present systolic and diastolic values but theoretically provide a more accurate BP measure than PPG signals since it is a direct pressure sensor inside the body. Our strategy establishes a critical benchmark for PPG performance, realistically calibrating expectations for PPG's BP estimation capabilities. Nonetheless, we compared the performance of our models using different signal-filtering conditions to evaluate the impact of filtering on the results. We evaluated our method using the AAMI and the BHS standards employing the VitalDB dataset. The N-IABP signals meet with AAMI standards for both Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), with errors of 1.29+-6.33mmHg for systolic pressure and 1.17+-5.78mmHg for systolic and diastolic pressure respectively for the raw N-IABP signal. In contrast, N-PPG signals, in their best setup, exhibited inferior performance than N-IABP, presenting 1.49+-11.82mmHg and 0.89+-7.27mmHg for systolic and diastolic pressure respectively. Our findings highlight the potential and limitations of employing PPG for BP estimation, showing that these signals contain information correlated to BP but may not be sufficient for predicting it accurately.Comment: 17 pages, 7 figures, 3 table

Quality Assessment of Photoplethysmography Signals For Cardiovascular Biomarkers Monitoring Using Wearable Devices

Photoplethysmography (PPG) is a non-invasive technology that measures changes in blood volume in the microvascular bed of tissue. It is commonly used in medical devices such as pulse oximeters and wrist worn heart rate monitors to monitor cardiovascular hemodynamics. PPG allows for the assessment of parameters (e.g., heart rate, pulse waveform, and peripheral perfusion) that can indicate conditions such as vasoconstriction or vasodilation, and provides information about microvascular blood flow, making it a valuable tool for monitoring cardiovascular health. However, PPG is subject to a number of sources of variations that can impact its accuracy and reliability, especially when using a wearable device for continuous monitoring, such as motion artifacts, skin pigmentation, and vasomotion. In this study, we extracted 27 statistical features from the PPG signal for training machine-learning models based on gradient boosting (XGBoost and CatBoost) and Random Forest (RF) algorithms to assess quality of PPG signals that were labeled as good or poor quality. We used the PPG time series from a publicly available dataset and evaluated the algorithm s performance using Sensitivity (Se), Positive Predicted Value (PPV), and F1-score (F1) metrics. Our model achieved Se, PPV, and F1-score of 94.4, 95.6, and 95.0 for XGBoost, 94.7, 95.9, and 95.3 for CatBoost, and 93.7, 91.3 and 92.5 for RF, respectively. Our findings are comparable to state-of-the-art reported in the literature but using a much simpler model, indicating that ML models are promising for developing remote, non-invasive, and continuous measurement devices.Comment: 9 page

Symmorphosis through dietary regulation: a combinatorial role for proteolysis, autophagy and protein synthesis in normalising muscle metabolism and function of hypertrophic mice after acute starvation

Animals are imbued with adaptive mechanisms spanning from the tissue/organ to the cellular scale which insure that processes of homeostasis are preserved in the landscape of size change. However we and others have postulated that the degree of adaptation is limited and that once outside the normal levels of size fluctuations, cells and tissues function in an aberant manner. In this study we examine the function of muscle in the myostatin null mouse which is an excellent model for hypertrophy beyond levels of normal growth and consequeces of acute starvation to restore mass. We show that muscle growth is sustained through protein synthesis driven by Serum/Glucocorticoid Kinase 1 (SGK1) rather than Akt1. Furthermore our metabonomic profiling of hypertrophic muscle shows that carbon from nutrient sources is being channelled for the production of biomass rather than ATP production. However the muscle displays elevated levels of autophagy and decreased levels of muscle tension. We demonstrate the myostatin null muscle is acutely sensitive to changes in diet and activates both the proteolytic and autophagy programmes and shutting down protein synthesis more extensively than is the case for wild-types. Poignantly we show that acute starvation which is detrimental to wild-type animals is beneficial in terms of metabolism and muscle function in the myostatin null mice by normalising tension production

Analysis of Proteasomal Proteolysis during the In Vitro Metacyclogenesis of Trypanosoma cruzi

Proteasomes are large protein complexes, whose main function is to degrade unnecessary or damaged proteins. The inhibition of proteasome activity in Trypanosoma cruzi blocks parasite replication and cellular differentiation. We demonstrate that proteasome-dependent proteolysis occurs during the cellular differentiation of T. cruzi from replicative non-infectious epimastigotes to non-replicative and infectious trypomastigotes (metacyclogenesis). No peaks of ubiquitin-mediated degradation were observed and the profile of ubiquitinated conjugates was similar at all stages of differentiation. However, an analysis of carbonylated proteins showed significant variation in oxidized protein levels at the various stages of differentiation and the proteasome inhibition also increased oxidized protein levels. Our data suggest that different proteasome complexes coexist during metacyclogenesis. The 20S proteasome may be free or linked to regulatory particles (PA700, PA26 and PA200), at specific cell sites and the coordinated action of these complexes would make it possible for proteolysis of ubiquitin-tagged proteins and oxidized proteins, to coexist in the cell

Comparative performance evaluation of hepatitis C virus genotyping based on the 5' untranslated region versus partial sequencing of the NS5B region of brazilian patients with chronic hepatitis C

<p>Abstract</p> <p>Background</p> <p>Genotyping of hepatitis C virus (HCV) has become an essential tool for prognosis and prediction of treatment duration. The aim of this study was to compare two HCV genotyping methods: reverse hybridization line probe assay (LiPA v.1) and partial sequencing of the NS5B region.</p> <p>Methods</p> <p>Plasma of 171 patients with chronic hepatitis C were screened using both a commercial method (LiPA HCV Versant, Siemens, Tarrytown, NY, USA) and different primers targeting the NS5B region for PCR amplification and sequencing analysis.</p> <p>Results</p> <p>Comparison of the HCV genotyping methods showed no difference in the classification at the genotype level. However, a total of 82/171 samples (47.9%) including misclassification, non-subtypable, discrepant and inconclusive results were not classified by LiPA at the subtype level but could be discriminated by NS5B sequencing. Of these samples, 34 samples of genotype 1a and 6 samples of genotype 1b were classified at the subtype level using sequencing of NS5B.</p> <p>Conclusions</p> <p>Sequence analysis of NS5B for genotyping HCV provides precise genotype and subtype identification and an accurate epidemiological representation of circulating viral strains.</p

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery

A high-throughput cloning system for reverse genetics in Trypanosoma cruzi

<p>Abstract</p> <p>Background</p> <p>The three trypanosomatids pathogenic to men, <it>Trypanosoma cruzi</it>, <it>Trypanosoma brucei </it>and <it>Leishmania major</it>, are etiological agents of Chagas disease, African sleeping sickness and cutaneous leishmaniasis, respectively. The complete sequencing of these trypanosomatid genomes represented a breakthrough in the understanding of these organisms. Genome sequencing is a step towards solving the parasite biology puzzle, as there are a high percentage of genes encoding proteins without functional annotation. Also, technical limitations in protein expression in heterologous systems reinforce the evident need for the development of a high-throughput reverse genetics platform. Ideally, such platform would lead to efficient cloning and compatibility with various approaches. Thus, we aimed to construct a highly efficient cloning platform compatible with plasmid vectors that are suitable for various approaches.</p> <p>Results</p> <p>We constructed a platform with a flexible structure allowing the exchange of various elements, such as promoters, fusion tags, intergenic regions or resistance markers. This platform is based on Gateway^®technology, to ensure a fast and efficient cloning system. We obtained plasmid vectors carrying genes for fluorescent proteins (green, cyan or yellow), and sequences for the <it>c-myc </it>epitope, and tandem affinity purification or polyhistidine tags. The vectors were verified by successful subcellular localization of two previously characterized proteins (<it>Tc</it>Rab7 and PAR 2) and a putative centrin. For the tandem affinity purification tag, the purification of two protein complexes (ribosome and proteasome) was performed.</p> <p>Conclusions</p> <p>We constructed plasmids with an efficient cloning system and suitable for use across various applications, such as protein localization and co-localization, protein partner identification and protein expression. This platform also allows vector customization, as the vectors were constructed to enable easy exchange of its elements. The development of this high-throughput platform is a step closer towards large-scale trypanosome applications and initiatives.</p

Racism as a determinant of health: a systematic review and meta-analysis

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants.<br /