Local intraspecific aggregation in phytoplankton model communities: spatial scales of occurrence and implications for coexistence.

The coexistence of multiple phytoplankton species despite their reliance on similar resources is often explained with mean-field models assuming mixed populations. In reality, observations of phytoplankton indicate spatial aggregation at all scales, including at the scale of a few individuals. Local spatial aggregation can hinder competitive exclusion since individuals then interact mostly with other individuals of their own species, rather than competitors from different species. To evaluate how microscale spatial aggregation might explain phytoplankton diversity maintenance, an individual-based, multispecies representation of cells in a hydrodynamic environment is required. We formulate a three-dimensional and multispecies individual-based model of phytoplankton population dynamics at the Kolmogorov scale. The model is studied through both simulations and the derivation of spatial moment equations, in connection with point process theory. The spatial moment equations show a good match between theory and simulations. We parameterized the model based on phytoplankters' ecological and physical characteristics, for both large and small phytoplankton. Defining a zone of potential interactions as the overlap between nutrient depletion volumes, we show that local species composition-within the range of possible interactions-depends on the size class of phytoplankton. In small phytoplankton, individuals remain in mostly monospecific clusters. Spatial structure therefore favours intra- over inter-specific interactions for small phytoplankton, contributing to coexistence. Large phytoplankton cell neighbourhoods appear more mixed. Although some small-scale self-organizing spatial structure remains and could influence coexistence mechanisms, other factors may need to be explored to explain diversity maintenance in large phytoplankton.

Advocacy Connection Team-Now educational program for headache fellows and patients/caregivers: Assessment of educational objectives.

OBJECTIVE: To assess for improvement in comfort in participating in advocacy for migraine and headache disorders and knowledge needed for successful advocacy. BACKGROUND: The Advocacy Connection Team (ACT)-Now program is an educational program offered through Miles for Migraine, a non-profit advocacy organization. It is designed to teach headache fellows and patients advocacy skills. METHODS: In a cross-sectional pre-test-post-test design, the 2021 ACT-Now cohort of 98 participants were administered a set of 11 pre-course survey questions identifying their role (healthcare provider/headache fellow or patient/caregiver), baseline knowledge of migraine-related disability and stigma, and baseline engagement and comfort with advocating. The post-course survey questions were the same as the pre-course questions, with the addition of one question assessing knowledge of migraine-related disability, additional questions addressing comfort levels advocating with insurance and policymakers, as well as creating an advocacy plan. RESULTS: For the pre-course survey, 69 participants responded and for the post-course survey, 40 participants responded. Compared to the pre-course survey, participants were able to correctly identify epidemiological data about migraine following the ACT-Now course (pre-course 46% correct, post-course 58% correct, p = 0.263). There was also an increase in the comfort level of participants in advocacy activities, including the creation of an advocacy action plan (pre-course 23% were "very comfortable" advocating, post-course 63%, p < 0.05). CONCLUSION: These results demonstrate that ACT-Now is effective at improving advocacy skills in a mixed cohort of patients and headache fellows, giving them the skills to create advocacy plans and engage with other patients and physicians, payers, and policymakers to create a more understanding, equitable and compassionate world for persons with migraine and other headache diseases.

T-wave morphology abnormalities in the STREAM stage 1 trial.

BACKGROUND: Shorter regimens for drug-resistant tuberculosis (DR-TB) have non-inferior efficacy compared with longer regimens, but QT prolongation is a concern. T-wave morphology abnormalities may be a predictor of QT prolongation. RESEARCH DESIGN AND METHODS: STREAM Stage 1 was a randomized controlled trial in rifampicin-resistant TB, comparing short and long regimens. All participants had regular ECGs. QT/QTcF prolongation (≥500 ms or increase in ≥60 ms from baseline) was more common on the short regimen which contained high-dose moxifloxacin and clofazimine. Blinded ECGs were selected from the baseline, early (weeks 1-4), and late (weeks 12-36) time points. T-wave morphology was categorized as normal or abnormal (notched, asymmetric, flat-wave, flat peak, or broad). Differences between groups were assessed using Chi-Square tests (paired/unpaired, as appropriate). RESULTS: Two-hundred participants with available ECGs at relevant times were analyzed (QT prolongation group n = 82; non-prolongation group n = 118). At baseline, 23% (45/200) of participants displayed abnormal T-waves, increasing to 45% (90/200, p < 0.001) at the late time point. Abnormalities were more common in participants allocated the Short regimen (75/117, 64%) than the Long (14/38, 36.8%, p = 0.003); these occurred prior to QT/QTcF ≥500 ms in 53% of the participants (Long 2/5; Short 14/25). CONCLUSIONS: T-wave abnormalities may help identify patients at risk of QT prolongation on DR-TB treatment. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02409290). Current Controlled Trial number, ISRCTN78372190.

Measurement of cigarette relighting: A common but understudied behavior.

OBJECTIVE: Relighting, i.e., extinguishing, saving, and later relighting and smoking unfinished cigarettes, appears prevalent, may be associated with nicotine dependence and negative health outcomes, yet is poorly understood. We estimate the prevalence, frequency, correlates of, and reasons for, cigarette relighting. METHODS: Survey respondents (n=676) were 18-45-year-old US-based Amazon Mechanical Turk (MTurk) participants who smoked cigarettes every/some days. Items assessed frequency of and reasons for relighting. Reported smoking sessions per day were compared to calculations based on reported cigarettes per day (CPD) and relighting frequency. RESULTS: Seventy-two percent of those who smoked reported relighting cigarettes. Reasons included not having time to finish (77%), not feeling like finishing (75%), saving money or avoiding wasting (70%), and making cigarettes last longer (59%). Nearly half (44%) relight to cut down and 34% to reduce harm. Hispanic (OR=1.73, CI:1.03-2.91) and non-Hispanic Black respondents (OR= 2.23, CI:1.20-4.10) had higher odds of relighting than others, as did those who smoke within 30minutes of waking (OR=2.45, CI:1.33-4.52) or wake up at night to smoke (OR=2.40, CI:1.68-3.44) (all ps <0.05). Respondents demonstrated low consistency in reporting the number of times they smoke (first-lit and relit) compared to calculations based on CPD and relighting frequency. CONCLUSIONS: Relighting is associated with race, ethnicity, nicotine dependence, and is often done to save money, cut down smoking, and reduce harm. Among those who relight, "smoking session" frequency seemed to be underestimated. Single item smoking frequency measures may not be ideal for individuals who smoke and relight.

Is having your cell phone the key to happiness, or does it really matter? Evidence from a randomized double-blind study.

BACKGROUND: Affect can influence people's perceptions, decisions, and the way they make sense of an experience. Some studies show that having one's cell phone removed will lead to negative emotional reactions, while others have found no significant impact on how we feel. In this paper we investigate the impact of cell phone possession and removal on participant's affective state. METHODS: We use a randomized double-blind procedure to examine whether cell phone removal enhances negativity, promotes positivity, or is emotionally inconsequential. We measure affect using a PANAS self-report scale as well as a less transparent temporal-estimation procedure. RESULTS: Our findings suggest that cell phone possession or removal has no influence on a person's affective state. CONCLUSIONS: Measured through both the PANAS self-report scale and temporal estimation task, affect remained consistent regardless of cell phone possession. These results suggest that cell phones may not carry the emotional weight often attributed to them. This finding challenges a common theme revolving around the negative emotional impact of cell phones and technology. Consequently, these findings may have important implications for the generally perceived notion that cell phones are having a negative effect on people's emotions.

Preventive treatment of migraine: Non-specific oral agents.

Migraine headache is highly prevalent and the most common neurologic disorder, affecting one billion people worldwide. It is also the most disabling condition in people under 50, with a huge impact on working ability, family, and social life. Access to effective preventive medication is important and may be considered if the patient has 6 or more migraine days per month, ineffective abortive agents, or disability on 2 or more days per month. Propranolol, metoprolol, candesartan, topiramate, divalproex, lisinopril, amitriptyline, and venlafaxine have the strongest evidence to support for use. Flunarizine and pizotifen may also be effective. Selection of preventive treatments is based on individual characteristics, comorbid conditions, efficacy, contraindications, side effects, cost, compliance, and drug. An adequate trial of migraine prophylaxis is usually 2 months at the target dose, and it is always important to re-evaluate indication for prophylactic use after a period of time.

The frequency of gene variant reclassification and its impact on clinical management in the inherited arrhythmia clinic.

BACKGROUND: Genetic testing in the inherited arrhythmia clinic informs risk stratification, clinical management, and family screening. Periodic review of variant classification is recommended as supporting evidence accrues over time. However, there is limited reporting of real-world data on the frequency and impact of variant reclassification. OBJECTIVE: The purpose of this study was to determine the burden of variant reclassification in our inherited arrhythmia clinic and the impact on clinical management. METHODS: Genetic testing reports for patients referred to our clinic from 2004-2020 were reviewed. Reported variants were reinvestigated using ClinVar, VarSome, and a literature review. Classification was updated using the American College of Medical Genetics and Genomics (ACMG) criteria and tested for association with arrhythmic events and modification of medical management. RESULTS: We identified 517 patients (median age 37 years) who underwent gene panel testing. A variant of uncertain significance (VUS) was reported for 94 patients (18.2%) and more commonly identified when using large gene panels (P <.001). A total of 28 of 87 unique VUSs (32.2%) were reclassified to pathogenic/likely pathogenic (n = 11) or benign/likely benign (n = 17). Of 138 originally reported pathogenic variants, 7 (5.1%) lacked support using ACMG criteria. Variant reclassification was not associated with arrhythmic events; however, it did impact genotype-specific counseling and future therapeutic options. CONCLUSION: In our large real-world patient cohort, we identify a clinically important proportion of both pathogenic variants and VUSs with evidence for reclassification. These findings highlight the need for informed pretest counseling, a regular structured review of variants reported in genetic testing, and the potential benefits to patients for supporting genotype-guided therapy.

Angiographic cross-filling between inferior petrosal sinuses and alteration of adrenocorticotropic hormone sampling results for tumor localization in Cushing disease.

OBJECTIVE: Inferior petrosal sinus (IPS) sampling (IPSS) is a diagnostic procedure used to guide diagnostic localization of imaging-negative adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas. However, the efficacy of IPSS has been suboptimal at accurately lateralizing the adenoma, reducing surgical cure rates and leading to unintended pituitary dysfunction due to the added exploration. One rationale for the occasional imprecision is the existence of additional petrosal sinus collateral channels that connect the IPS bilaterally, which may lead to false localization results during sampling. The aim of this study was to explore a potential connection between normal anatomical variation in the angioarchitecture of the IPSs and the ACTH results obtained in subsequent IPSS tests. METHODS: A retrospective review was performed on all cases between 1998 and 2013 involving patients at a single institution who underwent IPSS for radiographically equivocal pituitary microadenomas. Cases were reviewed for tumor laterality noted on either operative or pathology reports, as well as the presence of angiographic evidence of cross-filling between the sinuses. In addition, ACTH levels from the right and left IPSs were documented at baseline and at 2, 5, and 10 minutes after corticotropin-releasing hormone (CRH) administration. A ratio of the change in ACTH levels measured at the time of maximal response (10 minutes) versus the levels measured at the initial response (2 minutes) was computed for each patient and compared between patients by their angiographic cross-filling status. RESULTS: There were 41 patients with a histopathologically confirmed right- or left-sided ACTH-secreting pituitary microadenoma who underwent preoperative IPSS. Among these patients, 28 (68%) showed angiographic evidence of cross-filling between the IPSs, and 13 showed no cross-filling. On average, ACTH levels increased by a factor of 3.91 ± 0.77 in the contralateral IPS in patients with angiographic cross-filling, compared with a factor increase of only 1.80 ± 0.27 in patients without cross-filling (p = 0.014). In comparison, ACTH levels increased by a factor of 2.01 ± 0.57 in the ipsilateral IPS in patients with cross-filling, and by 8.78 ± 7.30 in those without cross-filling (p = 0.373). CONCLUSIONS: The presence of angiographic cross-filling, suggestive of a greater degree of vascular channel networking between the right and left IPS, is a significant factor influencing the measured rates of change of ACTH in IPSS and may impact the specificity of this test to accurately determine microadenoma laterality in the preoperative setting.

Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement.

Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs.

Primary hyperparathyroidism in patients with multiple endocrine neoplasia type 1: Impact of genotype and surgical approach on long-term postoperative outcomes.

BACKGROUND: Protein-truncating germline pathogenic variants in the N- and C-terminal exons (2, 9, and 10) of the MEN1 gene may be associated with aggressive pancreatic neuroendocrine tumors. However, the impact of these variants on parathyroid disease is poorly understood. We sought to investigate the effects of genotype and surgical approach on clinical phenotype and postoperative outcomes in patients with multiple endocrine neoplasia type 1 (MEN1)-related primary hyperparathyroidism. METHODS: We identified patients with MEN1 evaluated at our institution from 1985 to 2020 and stratified them by genotype, (truncating variants in exons 2, 9, or 10, or other variants), and index surgical approach, (less-than-subtotal parathyroidectomy [

Long-term association of ultra-short heart rate variability with cardiovascular events.

Heart rate variability (HRV) is a cardiac autonomic marker with predictive value in cardiac patients. Ultra-short HRV (usHRV) can be measured at scale using standard and wearable ECGs, but its association with cardiovascular events in the general population is undetermined. We aimed to validate usHRV measured using ≤ 15-s ECGs (using RMSSD, SDSD and PHF indices) and investigate its association with atrial fibrillation, major adverse cardiac events, stroke and mortality in individuals without cardiovascular disease. In the National Survey for Health and Development (n = 1337 participants), agreement between 15-s and 6-min HRV, assessed with correlation analysis and Bland-Altman plots, was very good for RMSSD and SDSD and good for PHF. In the UK Biobank (n = 51,628 participants, 64% male, median age 58), after a median follow-up of 11.5 (11.4-11.7) years, incidence of outcomes ranged between 1.7% and 4.3%. Non-linear Cox regression analysis showed that reduced usHRV from 15-, 10- and 5-s ECGs was associated with all outcomes. Individuals with low usHRV (< 20th percentile) had hazard ratios for outcomes between 1.16 and 1.29, p < 0.05, with respect to the reference group. In conclusion, usHRV from ≤ 15-s ECGs correlates with standard short-term HRV and predicts increased risk of cardiovascular events in a large population-representative cohort.

Presence of alcohol and other drug use within youth mental health presentations to the emergency department: A single-site retrospective observational study.

OBJECTIVE: Youth mental health is a growing issue, which can be worsened by alcohol and other drug (AOD) use. The present study aimed to characterise the association of AOD use in youth presenting to an ED with a mental health crisis. METHODS: A retrospective observational study of paediatric patients presenting with mental health concerns to a tertiary ED in New Zealand in 2019-2020, with an examination of use of alcohol or other drugs before presentation. RESULTS: There were 842 ED presentations, made up of 491 unique individuals, examined from the 2-year period. Overdose (63.1%) was the most common reason for presentation, with 39.9% of overdoses involving prescription-only medications, 36.7% over-the-counter, and 20.0% a combination. Seventy-four (8.8%) presentations had documented use of alcohol or other drugs (excluding those taken in overdose) before arrival, with alcohol (51 presentations), followed by cannabis (19 presentations), being the most commonly recorded drugs used. Concurrent AOD use was not associated with any significant difference in triage, length of stay or admission status. CONCLUSION: In New Zealand, it is not legal to sell alcohol to persons under 18 years; however, this was the most commonly identified drug impacting on youth mental health presentations. There is a known association between alcohol use and adverse mental health symptoms; therefore, efforts to decrease access to alcohol in this age group must continue, and harm reduction interventions to reduce clinically significant overdoses recommended.

Two-dimensional turbulence above topography: Vortices and potential vorticity homogenization.

The evolution of unforced and weakly damped two-dimensional turbulence over random rough topography presents two extreme states. If the initial kinetic energy [Formula: see text] is sufficiently high, then the topography is a weak perturbation, and evolution is determined by the spontaneous formation and mutual interaction of coherent axisymmetric vortices. High-energy vortices roam throughout the domain and mix the background potential vorticity (PV) to homogeneity, i.e., in the region between vortices, which is most of the domain, the relative vorticity largely cancels the topographic PV. If [Formula: see text] is low, then vortices still form but they soon become locked to topographic features: Anticyclones sit above topographic depressions and cyclones above elevated regions. In the low-energy case, with topographically locked vortices, the background PV retains some spatial variation. We develop a unified framework of topographic turbulence spanning these two extreme states of low and high energy. A main organizing concept is that PV homogenization demands a particular kinetic energy level [Formula: see text]. [Formula: see text] is the separator between high-energy evolution and low-energy evolution.

Single-cell Profiling Uncovers a Muc4-Expressing Metaplastic Gastric Cell Type Sustained by Helicobacter pylori-driven Inflammation.

Mechanisms for Helicobacter pylori (Hp)-driven stomach cancer are not fully understood. In a transgenic mouse model of gastric preneoplasia, concomitant Hp infection and induction of constitutively active KRAS (Hp+KRAS+) alters metaplasia phenotypes and elicits greater inflammation than either perturbation alone. Gastric single-cell RNA sequencing showed that Hp+KRAS+ mice had a large population of metaplastic pit cells that expressed the intestinal mucin Muc4 and the growth factor amphiregulin. Flow cytometry and IHC-based immune profiling revealed that metaplastic pit cells were associated with macrophage and T-cell inflammation. Accordingly, expansion of metaplastic pit cells was prevented by gastric immunosuppression and reversed by antibiotic eradication of Hp. Finally, MUC4 expression was significantly associated with proliferation in human gastric cancer samples. These studies identify an Hp-associated metaplastic pit cell lineage, also found in human gastric cancer tissues, whose expansion is driven by Hp-dependent inflammation. Significance: Using a mouse model, we have delineated metaplastic pit cells as a precancerous cell type whose expansion requires Hp-driven inflammation. In humans, metaplastic pit cells show enhanced proliferation as well as enrichment in precancer and early cancer tissues, highlighting an early step in the gastric metaplasia to cancer cascade.

Integration of genetic fine-mapping and multi-omics data reveals candidate effector genes for hypertension.

Genome-wide association studies of blood pressure (BP) have identified >1,000 loci, but the effector genes and biological pathways at these loci are mostly unknown. Using published association summary statistics, we conducted annotation-informed fine-mapping incorporating tissue-specific chromatin segmentation and colocalization to identify causal variants and candidate effector genes for systolic BP, diastolic BP, and pulse pressure. We observed 532 distinct signals associated with ≥2 BP traits and 84 with all three. For >20% of signals, a single variant accounted for >75% posterior probability, 65 were missense variants in known (SLC39A8, ADRB2, and DBH) and previously unreported BP candidate genes (NRIP1 and MMP14). In disease-relevant tissues, we colocalized >80 and >400 distinct signals for each BP trait with cis-eQTLs and regulatory regions from promoter capture Hi-C, respectively. Integrating mouse, human disorder, gene expression and tissue abundance data, and literature review, we provide consolidated evidence for 436 BP candidate genes for future functional validation and discover several potential drug targets.

Right coronary artery compromise following radiofrequency catheter ablation for supraventricular tachycardia: cases reports.

Background: Coronary compromise is a serious potential complication following catheter ablation; however, procedural details in the literature are often lacking, preventing the identification of learning opportunities. Case summary: We report two cases of right coronary compromise following catheter ablation for symptomatic supraventricular tachycardia. After radiofrequency energy delivery at the coronary sinus ostium in both cases, inferior lead ST-elevation was observed. Diagnostic coronary angiography identified an occluded posterior left ventricular branch of the coronary artery, and optical coherence tomography demonstrated a high thrombus burden at this location. Electrocardiographic ST-segments settled with implantation of a drug-eluting stent. Discussion: Coronary compromise was likely secondary to energy delivery during catheter ablation. This case series highlights the need for electrophysiologist to understand coronary anatomy relative to anatomical landmarks, to anticipate the risk of vascular injury as physical distance from the site of ablation is likely important. Risk for coronary compromise, while a rare complication, needs to be discussed with patients during the consenting process. We also demonstrate the importance of an efficient multi-disciplinary team process for managing acute procedural complications.

Primary Aldosteronism: A Pragmatic Approach to Diagnosis and Management.

Primary aldosteronism is a prevalent but underdiagnosed cause of hypertension, contributing to increased cardiovascular and cerebrovascular events and end-organ damage independent of blood pressure. Prompt diagnosis and treatment with targeted surgical or medical therapy reduce the risk of complications and improve prognosis. This review outlines a practical approach to diagnosis and management of primary aldosteronism for global practitioners.