Distributions of alcohol use and alcohol-caused death and disability in Canada: Defining alcohol harm density functions and new perspectives on the prevention paradox.

AIMS: The aims of this study were to examine the distribution of alcohol use and to define 'harm density functions' representing distributions of alcohol-caused health harm in Canada, by sex, towards better understanding which groups of drinkers experience the highest aggregate harms. DESIGN: This was an epidemiological modeling study using survey and administrative data on alcohol exposure, death and disability and risk relationships from epidemiological meta-analyses. SETTING: This work took place in Canada, 2019. PARTICIPANTS: Canadians aged 15 years or older participated. MEASUREMENTS: Measures included modeled life-time mean daily alcohol use in grams of pure alcohol (ethanol) per day, alcohol-caused deaths and alcohol-caused disability-adjusted life-years. FINDINGS: As a life-time average, more than half of Canadians aged 15+ (62.8% females, 46.9% males) use fewer than 10 g of pure alcohol per day (g/day). By volume, the top 10% of the population consume 45.9% of the total ethanol among males and 47.1% of the total ethanol among females. The remaining 90% of the population experience a slim majority of alcohol-caused deaths (males 55.3%, females 46.9%). Alcohol harm density functions compose the size of the using population and the risk experienced at each volume level to show that the population-level harm experienced is highest for males at 25 g/day and females at 13 g/day. CONCLUSIONS: Almost 50% of alcohol use in Canada is concentrated among the highest 10% of drinkers, but more than half of the alcohol-caused deaths in Canada in 2019 were experienced by the bottom 90% of the population by average volume, providing evidence for the prevention paradox. New alcohol harm density functions provide insight into the aggregate health harm experienced across the mean alcohol use spectrum and may therefore be used to help determine where alcohol policies should be targeted for highest efficacy.

A novel heuristic tool for selecting the best upgrading conditions for the removal of potentially toxic elements by soil washing.

Here, we propose two-parameter penalized attributive analysis, PPAA-U, a novel heuristic tool for selecting the best upgrading conditions (BUCs) for soil washing. Given a multi-component feed and a specific set of operating conditions, PPAA-U generates a quality index based on how well recoveries for key components are maximized while minimizing the yield. We demonstrate, through the calculation of families of curves, that this quality index is related linearly to recovery and to the inverse of the yield, meaning that reducing yield values is more important than maximizing recovery. To evaluate our method, electrostatic separation at 12 different voltages was carried out on soil samples from an ex-industrial site in Spain. Values of recovery, yield, and grade were analyzed using basic attributive analysis and PPAA-U with and without target-to-distance correction. Both methods identified the same optimal separation voltage, and the power of PPAA-U to correct for high variation in yields and recoveries was observed as a divergence between results produced by each method at low voltages where variation in these values was greatest. PPAA-U thus offers a convenient tool for soil washing optimization, and we suggest that it could be applied successfully to other industrial processes.

Inflammatory changes in the plasma and cerebrospinal fluid of patients with persistent pain and postpartum depression after elective Cesarean delivery: an exploratory prospective cohort study.

PURPOSE: Severe acute pain after Cesarean delivery increases the risk of developing persistent pain (~20% incidence) and postpartum depression (PPD) (~15% incidence). Both conditions contribute to maternal morbidity and mortality, yet early risk stratification remains challenging. Neuroinflammation has emerged as a key mechanism of persistent pain and depression in nonobstetric populations. Nevertheless, most studies focus on plasma cytokines, and the relationship between plasma and cerebrospinal fluid (CSF) cytokine levels is unclear. Our primary aim was to compare inflammatory marker levels between patients who developed the composite outcome of persistent pain and/or PPD vs those who did not. METHODS: We recruited term patients with singleton pregnancies undergoing elective Cesarean delivery under neuraxial anesthesia into an exploratory prospective cohort study. We collected baseline demographic, obstetric, and Edinburgh Postnatal Depression Scale information, and performed quantitative sensory tests. Plasma was collected preoperatively and 48 hr postoperatively. In the operating room, 10 mL of CSF was collected, followed by a standardized anesthetic. Intra- and postoperative management were according to standard practice. We obtained Edinburgh Postnatal Depression Scale and pain scores at six weeks and three months after delivery. The primary outcome was persistent pain and/or PPD at three months. We analyzed the difference in inflammatory marker levels between the groups (primary aim) using two-sided Mann-Whitney tests. RESULTS: Eighty participants were enrolled, and 63 patients completed the study; 23 (37%) experienced the primary outcome at three months. Preoperative plasma transforming growth factor beta 1 (TGF-ß1) concentration was higher in patients who developed the primary outcome compared with those who did not (median [interquartile range (IQR)], 2,879 [2,241-5,494] vs 2,292 [1,676-2,960] pg·mL-1; P = 0.04), while CSF IL-1ß concentration was higher in patients who developed the primary outcome than in those who did not (median [IQR], 0.36 [0.29-0.39] vs 0.30 [0.25-0.35] pg·mL-1; P = 0.03). CONCLUSIONS: We observed differential levels of plasma and CSF inflammatory biomarkers in patients who developed persistent pain and PPD compared with those who did not. We showed the feasibility of collecting plasma and CSF samples at Cesarean delivery, which may prove useful for future risk-stratification. STUDY REGISTRATION: ClinicalTrials.gov (NCT04271072); registered 17 February 2020.

RéSUMé: OBJECTIF: La douleur aiguë sévère après un accouchement par césarienne augmente le risque de douleur persistante (~20 % d'incidence) et de dépression post-partum (DPP) (~15 % d'incidence). Ces deux conditions contribuent à la morbidité et à la mortalité maternelles, mais la stratification précoce des risques demeure difficile. La neuroinflammation est apparue comme un mécanisme clé de la douleur persistante et de la dépression dans les populations non obstétricales. Néanmoins, la plupart des études se concentrent sur les cytokines plasmatiques, et la relation entre les taux de cytokines plasmatiques et de liquide céphalorachidien (LCR) n'est pas claire. Notre objectif principal était de comparer les taux de marqueurs inflammatoires entre les patient·es qui ont eu un résultat composite de douleur persistante et/ou de DPP vs les personnes qui n'en ont pas eu. MéTHODE: Nous avons recruté des patient·es à terme avec des grossesses uniques bénéficiant d'une césarienne programmée sous anesthésie neuraxiale dans une étude de cohorte prospective exploratoire. Nous avons recueilli des informations démographiques de base, obstétricales et tirées de l'Échelle de dépression postnatale d'Édimbourg, et effectué des tests sensoriels quantitatifs. Le plasma a été prélevé avant l'opération et 48 heures après l'opération. En salle d'opération, 10 mL de LCR ont été recueillis, suivis d'un anesthésie standardisée. La prise en charge per- et postopératoire était conforme à la pratique courante. Nous avons obtenu les scores sur l'Échelle de dépression postnatale d'Édimbourg et les scores de douleur six semaines et trois mois après l'accouchement. Le critère d'évaluation principal était la douleur persistante et/ou la DPP à trois mois. Nous avons analysé la différence dans les niveaux de marqueurs inflammatoires entre les groupes (objectif principal) en utilisant des tests bilatéraux de Mann-Whitney. RéSULTATS: Quatre-vingts personnes ont été recrutées et 63 patient·es ont terminé l'étude; 23 (37 %) ont rapporté le critère d'évaluation principal à trois mois. Le facteur TGF-ß1 (transforming growth factor beta 1) plasmatique préopératoire était plus élevé chez les patient·es qui ont manifesté le critère d'évaluation principal par rapport aux personnes qui ne l'ont pas manifesté (médiane [écart interquartile (ÉIQ)], 2879 [2241-5494] vs 2292 [1676­2960] pg·mL−1; P = 0,04), tandis que le IL-1ß dans le LCR était plus élevé chez les patient·es qui ont manifesté le critère d'évaluation principal que chez les personnes qui ne l'ont pas manifesté (médiane [ÉIQ], 0,36 [0,29-0,39] vs 0,30 [0,25­0,35] pg·mL−1; P = 0,03). CONCLUSION: Nous avons observé des taux différentiels de biomarqueurs inflammatoires plasmatiques et de LCR chez les patient·es qui ont manifesté une douleur persistante et une DPP par rapport aux personnes qui n'en ont pas manifesté. Nous avons montré la faisabilité de la collecte d'échantillons de plasma et de LCR lors de l'accouchement par césarienne, ce qui pourrait s'avérer utile pour la stratification future des risques. ENREGISTREMENT DE L'éTUDE: clinicaltrials.gov (NCT04271072); enregistrée le 17 février 2020.

Development of Iodinated Indocyanine Green Analogs as a Strategy for Targeted Therapy of Liver Cancer.

Liver cancer is one of the leading causes of cancer-related deaths, with a significant increase in incidence worldwide. Novel therapies are needed to address this unmet clinical need. Indocyanine green (ICG) is a broadly used fluorescence-guided surgery (FGS) agent for liver tumor resection and has significant potential for conversion to a targeted therapy. Here, we report the design, synthesis, and investigation of a series of iodinated ICG analogs (I-ICG), which can be used to develop ICG-based targeted radiopharmaceutical therapy. We applied a CRISPR-based screen to identify the solute carrier transporter, OATP1B3, as a likely mechanism for ICG uptake. Our lead I-ICG compound specifically localizes to tumors in mice bearing liver cancer xenografts. This study introduces the chemistry needed to incorporate iodine onto the ICG scaffold and defines the impact of these modifications on key properties, including targeting liver cancer in vitro and in vivo.

Conformational regulation and target-myristoyl switch of calcineurin B homologous protein 3.

Calcineurin B homologous protein 3 (CHP3) is an EF-hand Ca2+-binding protein involved in regulation of cancerogenesis, cardiac hypertrophy, and neuronal development through interactions with sodium/proton exchangers (NHEs) and signalling proteins. While the importance of Ca2+ binding and myristoylation for CHP3 function has been recognized, the underlying molecular mechanism remained elusive. In this study, we demonstrate that Ca2+ binding and myristoylation independently affect the conformation and functions of human CHP3. Ca2+ binding increased local flexibility and hydrophobicity of CHP3 indicative of an open conformation. The Ca2+-bound CHP3 exhibited a higher affinity for NHE1 and associated stronger with lipid membranes compared to the Mg2+-bound CHP3, which adopted a closed conformation. Myristoylation enhanced the local flexibility of CHP3 and decreased its affinity to NHE1 independently of the bound ion, but did not affect its binding to lipid membranes. The data exclude the proposed Ca2+-myristoyl switch for CHP3. Instead, a Ca2+-independent exposure of the myristoyl moiety is induced by binding of the target peptide to CHP3 enhancing its association to lipid membranes. We name this novel regulatory mechanism 'target-myristoyl switch'. Collectively, the interplay of Ca2+ binding, myristoylation, and target binding allows for a context-specific regulation of CHP3 functions.

Method To Diversify Cyanine Chromophore Functionality Enables Improved Biomolecule Tracking and Intracellular Imaging.

Heptamethine indocyanines are invaluable probes for near-infrared (NIR) imaging. Despite broad use, there are only a few synthetic methods to assemble these molecules, and each has significant limitations. Here, we report the use of pyridinium benzoxazole (PyBox) salts as heptamethine indocyanine precursors. This method is high yielding, simple to implement, and provides access to previously unknown chromophore functionality. We applied this method to create molecules to address two outstanding objectives in NIR fluorescence imaging. First, we used an iterative approach to develop molecules for protein-targeted tumor imaging. When compared to common NIR fluorophores, the optimized probe increases the tumor specificity of monoclonal antibody (mAb) and nanobody conjugates. Second, we developed cyclizing heptamethine indocyanines with the goal of improving cellular uptake and fluorogenic properties. By modifying both the electrophilic and nucleophilic components, we demonstrate that the solvent sensitivity of the ring-open/ring-closed equilibrium can be modified over a wide range. We then show that a chloroalkane derivative of a compound with tuned cyclization properties undergoes particularly efficient no-wash live cell imaging using organelle-targeted HaloTag self-labeling proteins. Overall, the chemistry reported here broadens the scope of accessible chromophore functionality, and, in turn, enables the discovery of NIR probes with promising properties for advanced imaging applications.

Reducing Knee Hyperextension With an Exoskeleton in Children and Adolescents With Genu Recurvatum: A Feasibility Study.

Genu recurvatum, or knee hyperextension, is a complex gait pattern with a variety of etiologies, and is often connected with knee weakness, lack of motor control, and spasticity. Because of the atypical forces placed on the soft tissues, early treatment or prevention of knee hyperextension may help prevent further degradation of the knee joint. In this study, we assessed the feasibility of a knee exoskeleton to mitigate hyperextension and increase swing range of motion in five children/adolescents who presented with unilateral genu recurvatum. Over the course of three visits, each participant practiced walking with the exoskeleton, which provided torque assistance during both stance and swing based on an impedance control law. In final validation trials, the exoskeleton was effective in reducing knee hyperextension (0.2 ± 4.7° average peak knee extension without exo to 9.9 ± 10.3° with exo) and improving swing range of motion by 14.0 ± 4.5° increase on average. However, while the exoskeleton was effective in normalizing the kinematics, it did not lead to improved spatio-temporal asymmetry measures. This work showcases a promising potential application of a robotic knee exoskeleton for improving the kinematic characteristics of genu recurvatum gait.

Valproic acid affects neurogenesis during early optic tectum development in zebrafish.

The mammalian superior colliculus and its non-mammalian homolog, the optic tectum (OT), are midbrain structures that integrate multimodal sensory inputs and guide non-voluntary movements in response to prevalent stimuli. Recent studies have implicated this structure as a possible site affected in autism spectrum disorder (ASD). Interestingly, fetal exposure to valproic acid (VPA) has also been associated with an increased risk of ASD in humans and animal models. Therefore, we took the approach of determining the effects of VPA treatment on zebrafish OT development as a first step in identifying the mechanisms that allow its formation. We describe normal OT development during the first 5 days of development and show that in VPA-treated embryos, neuronal specification and neuropil formation was delayed. VPA treatment was most detrimental during the first 3 days of development and did not appear to be linked to oxidative stress. In conclusion, our work provides a foundation for research into mechanisms driving OT development, as well as the relationship between the OT, VPA, and ASD. This article has an associated First Person interview with one of the co-first authors of the paper.

Atroposelective Negishi Coupling Optimization Guided by Multivariate Linear Regression Analysis: Asymmetric Synthesis of KRAS G12C Covalent Inhibitor GDC-6036.

An efficient asymmetric synthesis of a potent KRAS G12C covalent inhibitor, GDC-6036 (1), is reported. The synthesis features a highly atroposelective Negishi coupling to construct the key C-C bond between two highly functionalized pyridine and quinazoline moieties by employing a Pd/Walphos catalytic system. Statistical modeling by comparing computational descriptors of a range of Walphos chiral bisphosphine ligands to a training set of experimental results was used to inform the selection of the best ligand, W057-2, which afforded the desired Negishi coupling product (Ra)-3 in excellent selectivity. A subsequent telescoped reaction sequence of alkoxylation, global deprotection, and acrylamide formation, followed by a final adipate salt formation, furnished GDC-6036 (1) in 40% overall yield from starting materials pyridine 5 and quinazoline 6.

The I.3.2 developmental mutant has a single nucleotide deletion in the gene centromere identifier.

The mutation I.3.2 was previously identified in a FLP/FRT screen of chromosome 2R for conditional growth regulators. Here we report the phenotypic characterization and genetic mapping of I.3.2 by undergraduate students participating in Fly-CURE, a pedagogical program that teaches the science of genetics through a classroom research experience. We find that creation of I.3.2 cell clones in the developing eye-antennal imaginal disc causes a headless adult phenotype, suggestive of both autonomous and non-autonomous effects on cell growth or viability. We also identify the I.3.2 mutation as a loss-of-function allele of the gene centromere identifier ( cid ), which encodes centromere-specific histone H3 variant critical for chromosomal segregation.

Opioid Antagonists from the Orvinol Series as Potential Reversal Agents for Opioid Overdose.

The opioid crisis continues to claim many lives, with a particular issue being the ready availability and use (whether intentional or accidental) of fentanyl and fentanyl analogues. Fentanyl is both potent and longer-acting than naloxone, the standard of care for overdose reversal, making it especially deadly. Consequently, there is interest in opioid reversal agents that are better able to counter its effects. The orvinol series of ligands are known for their high-affinity binding to opioid receptors and often extended duration of action; generally, compounds on this scaffold show agonist activity at the kappa and the mu-opioid receptor. Diprenorphine is an unusual member of this series being an antagonist at mu and only a partial agonist at kappa-opioid receptors. In this study, an orvinol antagonist, 14, was designed and synthesized that shows no agonist activity in vitro and is at least as good as naloxone at reversing the effects of mu-opioid receptor agonists in vivo.

Biodiversity of Parasitic Hymenoptera Across Sky Islands of Arkansas, United States.

Sky islands are often areas of endemism and high species diversity around the world. In central North America, the Ozark and Ouachita Highlands contain numerous modestly high elevational islands that are slightly cooler and wetter than surrounding lowlands and these areas are known to contain many unique species. We studied parasitic Hymenoptera biodiversity on three sky islands in Arkansas, both in canopy and understory strata of mature post oak forests. We found that morphospecies diversity was high, and community structure varied both within (canopy versus understory) and between sky islands. Each mountaintop showed a high level of distinctiveness with few morphospecies found in multiple locations. The high intersky island variation indicates that individual sky islands in the region harbor unique Hymenoptera assemblages, a pattern that likely extends to the broader insect community. Our study suggests that these highland areas are important regions of North American biodiversity and that they should be evaluated individually for conservation efforts in order to preserve their distinctive community structure.

An Anticancer Rhenium Tricarbonyl Targets Fe-S Cluster Biogenesis in Ovarian Cancer Cells.

Target identification remains a critical challenge in inorganic drug discovery to deconvolute potential polypharmacology. Herein, we describe an improved approach to prioritize candidate protein targets based on a combination of dose-dependent chemoproteomics and treatment effects in living cancer cells for the rhenium tricarbonyl compound TRIP. Chemoproteomics revealed 89 distinct dose-dependent targets with concentrations of competitive saturation between 0.1 and 32 µM despite the broad proteotoxic effects of TRIP. Target-response networks revealed two highly probable targets of which the Fe-S cluster biogenesis factor NUBP2 was competitively saturated by free TRIP at nanomolar concentrations. Importantly, TRIP treatment led to a down-regulation of Fe-S cluster containing proteins and upregulated ferritin. Fe-S cluster depletion was further verified by assessing mitochondrial bioenergetics. Consequently, TRIP emerges as a first-in-class modulator of the scaffold protein NUBP2, which disturbs Fe-S cluster biogenesis at sub-cytotoxic concentrations in ovarian cancer cells.

Participation and Performance by Gender in Synchronous Online Lectures: Three Unique Case Studies during Emergency Remote Teaching.

Studies have documented that men's voices are generally heard more than women's voices in face-to-face undergraduate biology classes, and some performance gaps have also been documented. Some of the few studies on gender equity in traditional online biology education suggest that women participate more and perform better in asynchronous online courses compared to men. While much is known about emergency remote teaching during the COVID-19 pandemic exacerbating existing inequities generally, studies are needed about the impact of specific emergency remote teaching practices on specific groups such as women. In this study, we performed an in-depth investigation of three life sciences classrooms that utilized synchronous online lectures during the pandemic. We observed each class throughout the semester, quantified participation behaviors, and investigated the role of student gender. We also compared final course grades by gender. On average, we found that men participated more than women both verbally and by chat. These differences were not significant for each class individually, but the differences align with the face-to-face patterns seen in this population previously. Our results also hint that men's chat comments may be more likely to be acknowledged than women's chats by peers. We found evidence of greater performance disparities favoring men than seen previously before the pandemic, but not in all classes. We discuss implications for instructors conducting emergency remote teaching as well as the need for larger studies to test the replicability of our results.

Targeted Dual-Modal PET/SPECT-NIR Imaging: From Building Blocks and Construction Strategies to Applications.

Molecular imaging is an emerging non-invasive method to qualitatively and quantitively visualize and characterize biological processes. Among the imaging modalities, PET/SPECT and near-infrared (NIR) imaging provide synergistic properties that result in deep tissue penetration and up to cell-level resolution. Dual-modal PET/SPECT-NIR agents are commonly combined with a targeting ligand (e.g., antibody or small molecule) to engage biomolecules overexpressed in cancer, thereby enabling selective multimodal visualization of primary and metastatic tumors. The use of such agents for (i) preoperative patient selection and surgical planning and (ii) intraoperative FGS could improve surgical workflow and patient outcomes. However, the development of targeted dual-modal agents is a chemical challenge and a topic of ongoing research. In this review, we define key design considerations of targeted dual-modal imaging from a topological perspective, list targeted dual-modal probes disclosed in the last decade, review recent progress in the field of NIR fluorescent probe development, and highlight future directions in this rapidly developing field.

Breast-implant-associated anaplastic large-cell lymphoma.

Breast-implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is an uncommon, recently recognized disease that seems to occur only in relation with implants with textured surfaces. Most cases present with late-onset peri-implant effusion or fluid collections that develop more than 12 months after insertion of the implant. The diagnosis is reached by cytological analysis of fluid samples obtained by ultrasound-guided fine-needle aspiration. These patients usually have a good prognosis after surgical removal of the implant. A small percentage of patients present with a nodule or mass adjacent to the implant that usually develops late. In these cases, the diagnosis is reached by the histological analysis of core-needle biopsy specimens. These patients have a worse prognosis and require a combination of surgery and systemic chemotherapy. The main immunophenotypic characteristics of this lymphoma are intense expression of CD30 and a lack of expression of anaplastic lymphoma kinase (ALK). Here we present a case of BIA-ALCL in a patient with implants with a textured surface that presented with peri-implant effusion and incipient formation of a millimetric nodule and was treated with removal of the implant and bilateral capsulectomy. It is important to point out that the disease requires multidisciplinary management and that the Spanish Agency of Medicines and Medical Devices (AEMPS) should be notified when the diagnosis is confirmed.

Long-term morbidities following unintentional dural puncture in obstetric patients: A systematic review and meta-analysis.

STUDY OBJECTIVE: To investigate the association of unintentional dural puncture (UDP) and postdural puncture headache (PDPH) with the risk of chronic headache, backache, neckache and depression. We also investigated if epidural blood patch (EBP) is associated with reduced risk of these morbidities. DESIGN: Systematic review and meta-analysis. PATIENTS: Pregnant women who experienced UDP and/or PDPH versus those who had uneventful neuraxial procedures, and women who received EBP versus those who did not. INTERVENTIONS: None. MEASUREMENTS: Primary outcomes were headache, backache, and neckache lasting ≥12 months, and depression ≥1 month. Secondary outcomes included chronic headache, backache, and neckache persisting ≥1 and ≥ 6 months, and the effects of EBP on those outcomes at ≥1 and ≥ 12 months. Subgroup analyses of prospective studies and sensitivity analyses of primary outcomes excluding poor quality studies were performed. MAIN RESULTS: Twelve studies compared 6541 women with UDP and/or PDPH versus 1,004,510 with uncomplicated neuraxial procedures. Eight studies compared EBP (n = 3610) with no EBP (n = 3154). UDP and/or PDPH were associated with increased risk of headache (RR 3.95; 95%CI 2.13 to 7.34; I2 42%), backache (RR 2.72; 95%CI 2.04 to 3.62; I2 1%), and neckache (RR 8.09; 95%CI 1.03 to 63.35) persisting ≥12 months, and depression (RR 3.12; 95%CI 1.44 to 6.77; I2 90%) lasting ≥1 month. Results were consistent in analyses at ≥1 and ≥ 6 months, subgroup analyses of prospective studies, and after exclusion of one poor-quality study from our primary outcome. EBP was not associated with significant reduction in the risk of long-term morbidities. CONCLUSIONS: UDP and/or PDPH were associated with increased risk of chronic headache, backache, neckache, and depression. EBP was not associated with a significant reduction in those risks, but this conclusion is limited by the heterogeneity of current data and lack of information on the success of EBP in relieving acute PDPH symptoms.

Effect of Assistance Using a Bilateral Robotic Knee Exoskeleton on Tibiofemoral Force Using a Neuromuscular Model.

Tibiofemoral compression forces present during locomotion can result in high stress and risk damage to the knee. Powered assistance using a knee exoskeleton may reduce the knee load by reducing the work required by the muscles. However, the exact effect of assistance on the tibiofemoral force is unknown. The goal of this study was to investigate the effect of knee extension assistance during the early stance phase on the tibiofemoral force. Nine able-bodied adults walked on an inclined treadmill with a bilateral knee exoskeleton with assistance and with no assistance. Using an EMG-informed neuromusculoskeletal model, muscle forces were estimated, then utilized to estimate the tibiofemoral contact force. Results showed a 28% reduction in the knee moment, which resulted in approximately a 15% decrease in knee extensor muscle activation and a 20% reduction in subsequent muscle force, leading to a significant 10% reduction in peak and 9% reduction in average tibiofemoral contact force during the early stance phase (p < 0.05). The results indicate the tibiofemoral force is highly dependent on the knee kinetics and quadricep muscle activation due to their influence on knee extensor muscle forces, the primary contributor to the knee load.

Unleashing the full power of LHCb to probe stealth new physics.

In this paper, we describe the potential of the LHCb experiment to detect stealth physics. This refers to dynamics beyond the standard model that would elude searches that focus on energetic objects or precision measurements of known processes. Stealth signatures include long-lived particles and light resonances that are produced very rarely or together with overwhelming backgrounds. We will discuss why LHCb is equipped to discover this kind of physics at the Large Hadron Collider and provide examples of well-motivated theoretical models that can be probed with great detail at the experiment.