The Dynamics of Locomotor Neuromuscular Fatigue during Ramp-Incremental Cycling to Intolerance.

INTRODUCTION: Traditional neuromuscular fatigue assessments are not task-specific and are unable to characterize neuromuscular performance decline during dynamic whole-body exercise. This study used interleaved maximal isokinetic cycling efforts to characterize the dynamics of the decline in neuromuscular performance during ramp-incremental (RI) cycle ergometry exercise to intolerance. METHODS: Eleven young healthy participants (10 male/1 female) performed two RI cycle ergometry exercise tests to intolerance: [1] RI-exercise with peak isokinetic power (Piso) at 80 rev·min-1 measured at baseline and immediately at intolerance from a maximal ~6 s effort; [2] RI-exercise where additional Piso measurements were interleaved every 90 s to characterize the decline in neuromuscular performance during the RI-test. Muscle excitation was measured using EMG during all Piso assessments, and pulmonary gas exchange was measured throughout. RESULTS: Baseline Piso was 832 ± 140 W and RI-exercise reduced Piso to 349 ± 96 W at intolerance (p = 0.001), which was not different from flywheel power at intolerance (303 ± 96 W; p = 0.292). There was no reduction in Piso between baseline cycling and gas exchange threshold (GET; baseline Piso vs. mean Piso below GET: 828 ± 146 vs. 815 ± 149 W; p = 1.00). Piso fell progressively above GET until intolerance (Piso every 90 s above GET: 759 ± 139; 684 ± 141; 535 ± 144; 374 ± 117 W; each p < 0.05 vs. baseline and mean Piso below GET). Peak muscle excitation (EMG) was also reduced only above GET (73 ± 14 % of baseline, at intolerance; p < 0.05). However, the reduction in peak Piso preceded the reduction in peak muscle excitation. CONCLUSIONS: The dynamics of the decline in neuromuscular performance (reduction in Piso and EMG) during RI-exercise are consistent with known intensity-dependent metabolic and traditional pre-post neuromuscular fatigue responses to discrete bouts of constant-power exercise.

Establishing the health and wellbeing needs of mining host community in Brazil, Chile and Peru: a mixed-method approach to identify priority areas for action to help communities meet their SDG3 targets.

BACKGROUND: The global mining industry is an important partner in advancing the 2030 Agenda for Sustainable Development. In 2018, Anglo American plc published their Sustainable Mining Plan, containing a goal for improving health and wellbeing aligned with the Sustainable Development Goal 3 (SDG3) targets. Having formed an independent multidisciplinary research consortium, we designed and implemented a mixed-methods approach to attain a deeper understanding of SDG3 priorities within the local context of communities hosting Anglo American mining operations located in Latin America. METHODS: In 2019, within the host communities of three mining operations in Chile, three in Brazil, and one in Peru, we conducted a qualitative study which included stakeholder workshops and key informant interviews. We also quantitatively appraised existing health data. Findings emerging from the qualitative and quantitative assessments were compared to identify health and wellbeing priority areas for action relevant to each community. RESULTS: Across the three countries, 120 people took part in workshops and 35 in interviews. In these workshops and interviews, non-communicable diseases (SDG3.4), harmful alcohol consumption (SDG3.5), and pollution, particularly air pollution (SDG3.9), were consistently identified as areas for priority action. There were similarities in the reporting of individual, interpersonal, community, societal, and structural factors underlying these priority areas across the different communities. The availability of quantitative data was generally good at the state level, becoming increasing sparse as we focused on smaller geographies. The priorities identified in the quantitative assessments generally aligned with those highlighted in the qualitative data. CONCLUSIONS: We highlight the importance of engaging with local populations to understand and address health needs. To address the priorities identified, intervention packages tailored to the specific needs of host communities, that tackle associated upstream societal level factors, are required. To facilitate this, appropriate monitoring systems and epidemiological investigations should be implemented to better understand the local context and quantify health issues. In the host communities, it is essential for the mining sector to be a key health partner in promoting integrated programmes that contribute to achieving the priority objectives and targets aligned with the SDG3 agenda.

KRAS mutation allele frequency threshold alters prognosis in right-sided resected pancreatic cancer.

BACKGROUND: Next-generation sequencing (NGS) provides information on genetic mutations and mutant allele frequency in tumor specimens. We investigated the prognostic significance of KRAS mutant allele frequency in patients with right-sided pancreatic ductal adenocarcinoma (PDAC) treated with surgical resection. METHODS: A retrospective study reviewed patients who underwent surgical resection for PDAC and analyzed tumors with an in-house mutational panel. Microdissected samples were studied using an NGS-based assay to detect over 200 hotspot mutations in 42 genes (Pan42) commonly involved in PDAC. RESULTS: A total of 144 PDAC right-sided surgical patients with a Pan42 panel were evaluated between 2015 and 2020; 121 patients (84%) harbored a KRAS mutation. Detected mutant allele frequencies were categorized as less than 20% (low mKRAS, n = 92) or greater than or equal to 20% (high mKRAS, n = 29). High mKRAS (KRAS ≥ 20%) patients were noted to have shorter disease-free survival after surgery (11.5 ± 2.1 vs. 19.5 ± 3.5 months, p = 0.03), more advanced tumor stage (p = 0.02), larger tumors (3.6 vs. 2.7 cm, p = 0.001), greater tumor cellularity (26% vs. 18%, p = 0.001), and higher rate of distant recurrence (p = 0.03) than low mKRAS patients. CONCLUSION: This study demonstrates the importance of KRAS mutant allele frequency on pathological characteristics and prognosis in right-sided PDAC treated with surgery.

Margin-Positive Pancreatic Ductal Adenocarcinoma during Pancreaticoduodenectomy: Additional Resection Does Not Improve Survival.

BACKGROUND: The impact of resecting positive margins during pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDA) remains debated. Additionally, the survival benefit of resecting multiple positive margins is unknown. METHODS: We identified patients with PDA who underwent PD from 2006 to 2015. Pancreatic neck, bile duct, and uncinate frozen section margins were assessed before and after resection of positive margins. Survival curves were compared with log-rank tests. Multivariable Cox regression assessed the effect of margin status on overall survival. RESULTS: Of 501 patients identified, 17.3%, 5.3%, and 19.7% had an initially positive uncinate, bile duct, or neck margin, respectively. Among initially positive bile duct and neck margins, 77.8% and 67.0% were resected, respectively. Although median survival was decreased among patients with any positive margins (15.6 vs. 20.9 months; p = 0.006), it was similar among patients with positive bile duct or neck margins with or without R1 to R0 resection (17.0 vs. 15.6 months; p = 0.20). Median survival with and without positive uncinate margins was 13.8 vs. 19.7 months (p = 0.04). Uncinate margins were never resected. Resection of additional margins when the uncinate was concurrently positive was not associated with improved survival (p = 0.37). Patients with positive margins who received adjuvant therapy had improved survival, regardless of margin resection (p = 0.03). Adjuvant therapy was independently protective against death (hazard ratio 0.6, 95% CI 0.5-0.7). CONCLUSIONS: Positive PD margins at any position are associated with reduced overall survival; however, resection of additional margins may not improve survival, particularly with concurrently positive uncinate margins. Adjuvant chemotherapy improves survival with positive margins, regardless of resection.

Can corrections spread misinformation to new audiences? Testing for the elusive familiarity backfire effect.

Misinformation often continues to influence inferential reasoning after clear and credible corrections are provided; this effect is known as the continued influence effect. It has been theorized that this effect is partly driven by misinformation familiarity. Some researchers have even argued that a correction should avoid repeating the misinformation, as the correction itself could serve to inadvertently enhance misinformation familiarity and may thus backfire, ironically strengthening the very misconception that it aims to correct. While previous research has found little evidence of such familiarity backfire effects, there remains one situation where they may yet arise: when correcting entirely novel misinformation, where corrections could serve to spread misinformation to new audiences who had never heard of it before. This article presents three experiments (total N = 1718) investigating the possibility of familiarity backfire within the context of correcting novel misinformation claims and after a 1-week study-test delay. While there was variation across experiments, overall there was substantial evidence against familiarity backfire. Corrections that exposed participants to novel misinformation did not lead to stronger misconceptions compared to a control group never exposed to the false claims or corrections. This suggests that it is safe to repeat misinformation when correcting it, even when the audience might be unfamiliar with the misinformation.

Adult-Onset Immunoglobulin A Vasculitis.

Immunoglobulin A vasculitis (IgAV), formerly Henoch-Schönlein purpura vasculitis, is a vasculitis commonly seen in children and only rarely described in adult patients. IgAV can present as arthralgia, rash, discolored urine, acute kidney injury, and gastrointestinal symptoms. We present a case of a 56-year-old man who presented with 1 month of worsening abdominal pain followed by a bilateral lower extremity rash. Laboratory evaluation indicated an acute kidney injury. Computed tomography and colonoscopy revealed terminal ileitis while kidney biopsy confirmed a diagnosis of IgAV.

Quantifying susceptibility of marine invertebrate biocomposites to dissolution in reduced pH.

Ocean acidification threatens many ecologically and economically important marine calcifiers. The increase in shell dissolution under the resulting reduced pH is an important and increasingly recognized threat. The biocomposites that make up calcified hardparts have a range of taxon-specific compositions and microstructures, and it is evident that these may influence susceptibilities to dissolution. Here, we show how dissolution (thickness loss), under both ambient and predicted end-century pH (approx. 7.6), varies between seven different bivalve molluscs and one crustacean biocomposite and investigate how this relates to details of their microstructure and composition. Over 100 days, the dissolution of all microstructures was greater under the lower pH in the end-century conditions. Dissolution of lobster cuticle was greater than that of any bivalve microstructure, despite its calcite mineralogy, showing the importance of other microstructural characteristics besides carbonate polymorph. Organic content had the strongest positive correlation with dissolution when all microstructures were considered, and together with Mg/Ca ratio, explained 80-90% of the variance in dissolution. Organic content, Mg/Ca ratio, crystal density and mineralogy were all required to explain the maximum variance in dissolution within only bivalve microstructures, but still only explained 50-60% of the variation in dissolution.

Pyogenic Liver Abscess with No Predisposing Risk Factors.

Pyogenic liver abscesses (PLA) are an uncommon cause of hospitalization in the United States. The majority of such cases are polymicrobial and are most commonly caused by seeding of infection from the biliary system. PLA is frequently associated with specific comorbidities such as diabetes mellitus, history of liver transplant, underlying hepatobiliary, or pancreatic disease. Herein, we describe a 47-year-old healthy male with no known risk factors associated with PLA who presented to the hospital with acute fever, abdominal pain, and dark colored urine. Initially the patient had a negative right upper quadrant ultrasound. However, the patient continued to have persistent fevers and abnormal liver biochemistries with negative liver serology that led to checking a magnetic resonance cholangiopancreatography which suggested multiple liver abscesses. Computer tomography guided aspiration revealed a monobacterial Streptococcus species within the abscess, which is commonly associated with arterial bacteremia as a source of PLA. Arterial bacteremia is one of most rare causes of PLA. The patient's septic workup was negative for any source of infection. This case demonstrates a patient with no risk factors who was diagnosed with PLA caused by apparent arterial bacteremia with no clear source of infection.

Interstitial Lung Disease in the Elderly.

BACKGROUND: Despite the relationship between idiopathic pulmonary fibrosis (IPF) and advancing age, little is known about the epidemiology of interstitial lung disease (ILD) in the elderly. We describe the diagnoses, clinical characteristics, and outcomes of patients who were elderly at the time of ILD diagnosis. METHODS: Among subjects from a prospective cohort study of ILD, elderly was defined as age ≥ 70 years. Diagnoses were derived from a multidisciplinary review. Differences between elderly and nonelderly groups were determined using the χ2 test and analysis of variance. RESULTS: Of the 327 subjects enrolled, 80 (24%) were elderly. The majority of elderly subjects were white men. The most common diagnoses were unclassifiable ILD (45%), IPF (34%), connective tissue disease (CTD)-ILD (11%), and hypersensitivity pneumonitis (8%). Most elderly subjects (74%) with unclassifiable ILD had an imaging pattern inconsistent with usual interstitial pneumonia (UIP). There were no significant differences in pulmonary function or 3-year mortality between nonelderly and elderly subjects combined or in a subgroup analysis of those with IPF. CONCLUSIONS: Although IPF was the single most common diagnosis, the majority of elderly subjects had non-IPF ILD. Our findings highlight the need for every patient with new-onset ILD, regardless of age, to be surveyed for exposures and findings of CTD. Unclassifiable ILD was common among the elderly, but for most, the radiographic pattern was inconsistent with UIP. Although the effect of ILD may be more pronounced in the elderly due to reduced global functionality, ILD was not more severe or aggressive in this group.

Stigmergic gene transfer and emergence of universal coding.

We consider a simple information-theoretic model for evolutionary dynamics approaching the "coding threshold," where the capacity to symbolically represent nucleic acid sequences emerges in response to a change in environmental conditions. We study the conditions when a coupling between the dynamics of a "proto-cell" and its proto-symbolic representation becomes beneficial in terms of preserving the proto-cell's information in a noisy environment. In particular, we are interested in understanding the behavior at the "error threshold" level, which, in our case, turns out to be a whole "error interval." The useful coupling is accompanied by self-organization of internal processing, i.e., an increase in complexity within the evolving system. Second, we study whether and how different proto-cells can stigmergically share such information via a joint encoding, even if they have slightly different individual dynamics. Implications for the emergence of biological genetic code are discussed.