Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty.

This study explores how researchers' analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers' expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each team's workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers' results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.

Hourglass, a rapid analysis framework for heterogeneous bioimaging data, identifies sex disparity in IL-6/STAT3-associated immune phenotypes in pancreatic cancer.

Integration and mining of bioimaging data remains a challenge and lags behind the rapidly expanding digital pathology field. We introduce Hourglass, an open-access analytical framework that streamlines biology-driven visualization, interrogation, and statistical assessment of multiparametric datasets. Cognizant of tissue and clinical heterogeneity, Hourglass systematically organizes observations across spatial and global levels and within patient subgroups. Applied to an extensive bioimaging dataset, Hourglass promptly consolidated a breadth of known interleukin-6 (IL-6) functions via its downstream effector STAT3 and uncovered a so-far unknown sexual dimorphism in the IL-6/STAT3-linked intratumoral T-cell response in human pancreatic cancer. As an R package and cross-platform application, Hourglass facilitates knowledge extraction from multi-layered bioimaging datasets for users with or without computational proficiency and provides unique and widely accessible analytical means to harness insights hidden within heterogeneous tissues at the sample and patient level. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Systemic inflammatory prognostic scores in advanced pancreatic adenocarcinoma.

BACKGROUND: Systemic inflammatory scores may aid prognostication and patient selection for trials. We compared five scores in advanced pancreatic adenocarcinoma (PDAC). METHODS: Unresectable/metastatic PDAC patients enrolled in the Comprehensive Molecular Characterisation of Advanced Pancreatic Ductal Adenocarcinoma for Better Treatment Selection trial (NCT02750657) were included. Patients had pre-treatment biopsies for whole genome and RNA sequencing. CD8 immunohistochemistry was available in a subset. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, Prognostic Nutritional Index, Gustave Roussy Immune Score (GRIm-S), and Memorial Sloan Kettering Prognostic Score (MPS) were calculated. Overall survival (OS) was estimated using Kaplan-Meier methods. Associations between inflammatory scores, clinical/genomic characteristics, and OS were analysed. RESULTS: We analysed 263 patients. High-risk NLR, GRIm-S and MPS were poorly prognostic. The GRIm-S had the highest predictive ability: median OS 6.4 vs. 10 months for high risk vs. low-risk (P < 0.001); HR 2.26 (P < 0.001). ECOG ≥ 1, the basal-like subtype, and low-HRDetect were additional poor prognostic factors (P < 0.01). Inflammatory scores did not associate with RNA-based classifiers or homologous recombination repair deficiency genotypes. High-risk MPS (P = 0.04) and GRIm-S (P = 0.02) patients had lower median CD8 + tumour-infiltrating lymphocytes. CONCLUSIONS: Inflammatory scores incorporating NLR have prognostic value in advanced PDAC. Understanding immunophenotypes of poor-risk patients and using these scores in trials will advance the field.

Aortic stenosis in the time of COVID-19: Development and outcomes of a rapid turnaround TAVI service.

The COVID-19 pandemic has resulted in the cancellation of many elective surgical procedures. This has led to reports of an increase in mortality for patients with non-Covid health conditions due to delayed definitive management. Patients with severe aortic stenosis have a high annual mortality if left untreated. These patients are at risk due to the reduced number of surgical aortic valve replacements and competition for intensive care facilities during the COVID-19 pandemic. This case series suggests that the minimally invasive transcatheter aortic valve implantation is safe to continue during the COVID-19 pandemic with adjustments to the patient pathway to minimize hospital stay and to reduce patient and staff exposure. This helps to reduce the delay of definitive treatment for patients with severe aortic stenosis.

Structural Brain Differences Between Cognitively Impaired Patients With and Without Apathy.

OBJECTIVE: Since apathy increases in prevalence with severity of dementia pathology, we sought to distinguish concomitant neurodegenerative processes from brain differences associated with apathy in persons with mild cognitive impairment (MCI) and Alzheimer's Disease (AD). We examined relative structural brain differences between case-control matched cognitively impaired patients with and without apathy. DESIGN: Cross-sectional case-control study. SETTING: Fifty-eight clinical sites in phase 2 of the AD Neuroimaging Initiative across the United States and Canada. PARTICIPANTS: The ≥ 55 years of age with MCI or AD dementia and no major neurological disorders aside from suspected incipient AD dementia. Participants with apathy (n=69) were age-, sex-, apolipoprotein E ε4 allele carrier status-, Mini-Mental State Exam score-, and MCI or AD dementia diagnosis-matched to participants without apathy (n=149). INTERVENTIONS: The 3-tesla T1-weighted MRI scan and neurocognitive assessments. Using the Neuropsychiatric Inventory apathy domain scores, participants were dichotomized into a with-apathy group (score ≥ 1) and a without-apathy group (score = 0). MEASUREMENTS: Cortical thicknesses from 24 a priori regions of interest involved in frontostriatal circuits and frontotemporal association areas. RESULTS: False-discovery rate adjusted within-group comparisons between participants with apathy and participants without apathy showed thinner right medial orbitofrontal (mOFC; meandifference(MD)±standarderrorofMD(SE)=-0.0879±0.0257mm; standardizedMD(d)=-0.4456) and left rostral anterior cingulate (rACC; MD±SE=-0.0905±0.0325mm; d=-0.3574) cortices and thicker left middle temporal cortices (MTC; MD±SE=0.0688±0.0239mm; d=0.3311) in those with apathy. CONCLUSION: Atrophy of the right mOFC and left rACC and sparing of atrophy in the left MTC are associated with apathy in cognitively impaired persons.

Inhibiting α5 Subunit-Containing γ-Aminobutyric Acid Type A Receptors Attenuates Cognitive Deficits After Traumatic Brain Injury.

OBJECTIVES: Cognitive deficits after traumatic brain injury are a leading cause of disability worldwide, yet no effective pharmacologic treatments exist to improve cognition. Traumatic brain injury increases proinflammatory cytokines, which trigger excess function of α5 subunit-containing γ-aminobutyric acid type A receptors. In several models of brain injury, drugs that inhibit α5 subunit-containing γ-aminobutyric acid type A receptor function improve cognitive performance. Thus, we postulated that inhibiting α5 subunit-containing γ-aminobutyric acid type A receptors would improve cognitive performance after traumatic brain injury. In addition, because traumatic brain injury reduces long-term potentiation in the hippocampus, a cellular correlate of memory, we studied whether inhibition of α5 subunit-containing γ-aminobutyric acid type A receptors attenuated deficits in long-term potentiation after traumatic brain injury. DESIGN: Experimental animal study. SETTING: Research laboratory. SUBJECTS: Adult male mice and hippocampal brain slices. INTERVENTIONS: Anesthetized mice were subjected to traumatic brain injury with a closed-head, free-weight drop method. One week later, the mice were treated with L-655,708 (0.5 mg/kg), an inhibitor that is selective for α5 subunit-containing γ-aminobutyric acid type A receptors, 30 minutes before undergoing behavioral testing. Problem-solving abilities were assessed using the puzzle box assay, and memory performance was studied with novel object recognition and object place recognition assays. In addition, hippocampal slices were prepared 1 week after traumatic brain injury, and long-term potentiation was studied using field recordings in the cornu Ammonis 1 region of slices that were perfused with L-655,708 (100 nM). MEASUREMENTS AND MAIN RESULTS: Traumatic brain injury increased the time required to solve difficult but not simple tasks in the puzzle box assay and impaired memory in the novel object recognition and object place recognition assays. L-655,708 improved both problem solving and memory in the traumatic brain injury mice. Traumatic brain injury reduced long-term potentiation in the hippocampal slices, and L-655,708 attenuated this reduction. CONCLUSIONS: Pharmacologic inhibition of α5 subunit-containing γ-aminobutyric acid type A receptors attenuated cognitive deficits after traumatic brain injury and enhanced synaptic plasticity in hippocampal slices. Collectively, these results suggest that α5 subunit-containing γ-aminobutyric acid type A receptors are novel targets for pharmacologic treatment of traumatic brain injury-induced persistent cognitive deficits.

Dexmedetomidine Prevents Excessive γ-Aminobutyric Acid Type A Receptor Function after Anesthesia.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Postoperative delirium is associated with poor long-term outcomes and increased mortality. General anesthetic drugs may contribute to delirium because they increase cell-surface expression and function of α5 subunit-containing γ-aminobutyric acid type A receptors, an effect that persists long after the drugs have been eliminated. Dexmedetomidine, an α2 adrenergic receptor agonist, prevents delirium in patients and reduces cognitive deficits in animals. Thus, it was postulated that dexmedetomidine prevents excessive function of α5 γ-aminobutyric acid type A receptors. METHODS: Injectable (etomidate) and inhaled (sevoflurane) anesthetic drugs were studied using cultured murine hippocampal neurons, cultured murine and human cortical astrocytes, and ex vivo murine hippocampal slices. γ-Aminobutyric acid type A receptor function and cell-signaling pathways were studied using electrophysiologic and biochemical methods. Memory and problem-solving behaviors were also studied. RESULTS: The etomidate-induced sustained increase in α5 γ-aminobutyric acid type A receptor cell-surface expression was reduced by dexmedetomidine (mean ± SD, etomidate: 146.4 ± 51.6% vs. etomidate + dexmedetomidine: 118.4 ± 39.1% of control, n = 8 each). Dexmedetomidine also reduced the persistent increase in tonic inhibitory current in hippocampal neurons (etomidate: 1.44 ± 0.33 pA/pF, n = 10; etomidate + dexmedetomidine: 1.01 ± 0.45 pA/pF, n = 9). Similarly, dexmedetomidine prevented a sevoflurane-induced increase in the tonic current. Dexmedetomidine stimulated astrocytes to release brain-derived neurotrophic factor, which acted as a paracrine factor to reduce excessive α5 γ-aminobutyric acid type A receptor function in neurons. Finally, dexmedetomidine attenuated memory and problem-solving deficits after anesthesia. CONCLUSIONS: Dexmedetomidine prevented excessive α5 γ-aminobutyric acid type A receptor function after anesthesia. This novel α2 adrenergic receptor- and brain-derived neurotrophic factor-dependent pathway may be targeted to prevent delirium.

Age-specific trends of atrial fibrillation-related ischaemic stroke and transient ischaemic attack, anticoagulant use and risk factor profile in Chinese population: a 15-year study.

BACKGROUND: Prevalence of atrial fibrillation (AF) is increasing globally, and the fivefold increase in stroke risk constitutes significant healthcare burden. AIMS: We aim to evaluate the trends of AF-related stroke and transient ischaemic attack (AF-stroke/TIA), prior anticoagulant use and their risk factors in different age groups in Chinese population. METHODS: Data were retrieved from the stroke registry at Prince of Wales Hospital. We compared the data at 5-year intervals over a 15-year period (years 1999, 2004, 2009 and 2014). RESULTS: A total of 3894 patients were included, 712 patients had AF-stroke/TIA. Over the 15 years, the total number of ischaemic stroke/TIA fluctuated slightly during the period from year 1999 to 2009, and increased by 21.5% in the year 2014. While AF-stroke/TIA increased continuously with time by 282.1%. Increasing trend of AF-stroke/TIA was observed in all age groups. Absolute growth was highest in patients aged ≥80 years; relative growth was most pronounced in those between 65 and 72 years (>3.5 fold increase). Throughout the 15 years, >70% of AF-stroke/TIA occurred in non-anticoagulated patients, and this proportion increased with age. Increasing trends in both hypertension and ischaemic heart disease were also observed in patients with AF aged ≥73 years. CONCLUSION: AF-stroke/TIA has increased continuously by >2.5 fold in Chinese population over a 15-year period, with the majority of AF-stroke/TIA occurring in non-anticoagulated patients. Strategic planning is needed to optimise anticoagulant use, particularly non-vitamin K antagonist oral anticoagulants in elderly patients, low-income group and those with ischaemic heart disease requiring concomitant antiplatelet therapy.

Colonoscopy after CT-diagnosed acute diverticulitis: Is it really necessary?

BACKGROUND: Computed tomography (CT) scans are commonly used to diagnose acute diverticulitis, but there are overlapping features between diverticulitis and colorectal cancer (CRC) on imaging studies. Hence, colonoscopy is typically recommended after an episode of acute diverticulitis to rule out underlying malignancy. Currently, 64-slice multidetector CT scanners are capable of providing higher-resolution images and may be able to distinguish malignancy from diverticular inflammation. We aimed to determine the prevalence of CRC among patients with CT-diagnosed acute diverticulitis. METHODS: We performed a retrospective study of patients with acute diverticulitis diagnosed on CT scan between December 2005 and December 2010 at St. Paul's Hospital, Vancouver, BC. Nonresidents were excluded. We reviewed CT scan reports that included the term "diverticulitis," reports of follow-up colonic evaluation within 1 year of diagnosis and pathology results. We queried the provincial cancer registry to ensure no cases of CRC were missed. RESULTS: A total of 293 patients had acute diverticulitis diagnosed on CT scan, but 8 were nonresidents and were excluded. Of the 285 included in the analysis, the mean age was 59.4 ± 15.1 years, and 167 (58.6%) were men. Among the 114 patients who underwent follow-up evaluation, malignancy was diagnosed in 4 (3.5%). The overall prevalence of malignancy among patients with CT-diagnosed diverticulitis was 1.4%. CONCLUSION: Routine endoscopic evaluation after an episode of diverticulitis diagnosed with high-resolution CT scan does not appear to be necessary. Selective approach in patients with protracted clinical course or those with mass lesion/obstruction on CT scan may be of benefit.

CONTEXTE: La tomodensitométrie (TDM) est couramment utilisée pour le diagnostic de la diverticulite aiguë, mais des caractéristiques sont communes à la diverticulite et au cancer colorectal (CCR) aux épreuves d'imagerie. On recommande donc en général la coloscopie après un épisode de diverticulite aiguë pour écarter un diagnostic de cancer sous-jacent. À l'heure actuelle, les appareils de TDM multidétecteurs à 64 barrettes peuvent fournir des images de haute résolution et permettent même de distinguer le cancer d'une inflammation diverticulaire. Nous avons voulu déterminer la prévalence du CCR chez les patients ayant présenté une diverticulite aiguë diagnostiquée par TDM. MÉTHODES: Nous avons procédé à une étude rétrospective sur des patients porteurs d'une diverticulite aiguë diagnostiquée à l'aide de TDM entre décembre 2005 et décembre 2010 à l'Hôpital St. Paul's de Vancouver, en Colombie-Britannique. Les non-résidents ont été exclus. Nous avons examiné les rapports de TDM incluant le terme « diverticulite ¼, les rapports d'examens du côlon au cours de l'année suivant le diagnostic et les rapports d'anatomopathologie. Nous avons interrogé le registre provincial sur le cancer pour nous assurer qu'aucun cas de CCR ne nous avait échappé. RÉSULTATS: En tout, 293 patients ont reçu un diagnostic de diverticulite à l'aide de la TDM; 8 étaient des non-résidents et ont été exclus. Parmi les 285 patients inclus dans l'analyse, l'âge moyen était de 59,4 ± 15,1 ans et 167 (58,6 %) étaient des hommes. Parmi les 114 patients qui ont subi un examen de suivi, le cancer a été diagnostiqué chez 4 (3,5 %). La prévalence globale du cancer chez les patients porteurs d'un diagnostic de diverticulite posé par TDM était de 1,4 %. CONCLUSION: L'évaluation endoscopique de routine après un épisode de diverticulite diagnostiquée à l'aide d'une TDM de haute résolution ne semble pas nécessaire. Une approche sélective chez les patients qui présentent une évolution clinique lente ou ceux qui présentent une lésion ou obstruction tumorale à la TDM pourrait être utile.

Porous Precision-Templated 40 µm Pore Scaffolds Promote Healing through Synergy in Macrophage Receptor with Collagenous Structure and Toll-Like Receptor Signaling.

Porous precision-templated scaffolds (PTS) with uniform, interconnected, 40 µm pores have shown favorable healing outcomes and a reduced foreign body reaction (FBR). Macrophage receptor with collagenous structure (MARCO) and toll-like receptors (TLRs) have been identified as key surface receptors in the initial inflammatory phase of wound healing. However, the role of MARCO and TLRs in modulating monocyte and macrophage phenotypes within PTS remains uncharacterized. In this study, we demonstrate a synergetic relationship between MARCO and TLR signaling in cells inhabiting PTS, where induction with TLR3 or TLR4 agonists to 40 µm scaffold-resident cells upregulates the transcription of MARCO. Upon deletion of MARCO, the prohealing phenotype within 40 µm PTS polarizes to a proinflammatory and profibrotic phenotype. Analysis of downstream TLR signaling shows that MARCO is required to attenuate nuclear factor kappa B (NF-κB) inflammation in 40 µm PTS by regulating the transcription of inhibitory NFKB inhibitor alpha (NFKBIA) and interleukin-1 receptor-associated kinase 3 (IRAK-M), primarily through a MyD88-dependent signaling pathway. Investigation of implant outcome in the absence of MARCO demonstrates an increase in collagen deposition within the scaffold and the development of tissue fibrosis. Overall, these results further our understanding of the molecular mechanisms underlying MARCO and TLR signaling within PTS. Impact statement Monocyte and macrophage phenotypes in the foreign body reaction (FBR) are essential for the development of a proinflammatory, prohealing, or profibrotic response to implanted biomaterials. Identification of key surface receptors and signaling mechanisms that give rise to these phenotypes remain to be elucidated. In this study, we report a synergistic relationship between macrophage receptor with collagenous structure (MARCO) and toll-like receptor (TLR) signaling in scaffold-resident cells inhabiting porous precision-templated 40 µm pore scaffolds through a MyD88-dependent pathway that promotes healing. These findings advance our understanding of the FBR and provide further evidence that suggests MARCO, TLRs, and fibrosis may be interconnected.

Disease Progression Patterns of Brain Morphology in Schizophrenia: More Progressed Stages in Treatment Resistance.

BACKGROUND AND HYPOTHESIS: Given the heterogeneity and possible disease progression in schizophrenia, identifying the neurobiological subtypes and progression patterns in each patient may lead to novel biomarkers. Here, we adopted data-driven machine-learning techniques to identify the progression patterns of brain morphological changes in schizophrenia and investigate the association with treatment resistance. STUDY DESIGN: In this cross-sectional multicenter study, we included 177 patients with schizophrenia, characterized by treatment response or resistance, with 3D T1-weighted magnetic resonance imaging. Cortical thickness and subcortical volumes calculated by FreeSurfer were converted into z scores using 73 healthy controls data. The Subtype and Stage Inference (SuStaIn) algorithm was used for unsupervised machine-learning analysis. STUDY RESULTS: SuStaIn identified 3 different subtypes: (1) subcortical volume reduction (SC) type (73 patients), in which volume reduction of subcortical structures occurs first and moderate cortical thinning follows, (2) globus pallidus hypertrophy and cortical thinning (GP-CX) type (42 patients), in which globus pallidus hypertrophy initially occurs followed by progressive cortical thinning, and (3) cortical thinning (pure CX) type (39 patients), in which thinning of the insular and lateral temporal lobe cortices primarily happens. The remaining 23 patients were assigned to baseline stage of progression (no change). SuStaIn also found 84 stages of progression, and treatment-resistant schizophrenia showed significantly more progressed stages than treatment-responsive cases (P = .001). The GP-CX type presented earlier stages than the pure CX type (P = .009). CONCLUSIONS: The brain morphological progressions in schizophrenia can be classified into 3 subtypes, and treatment resistance was associated with more progressed stages, which may suggest a novel biomarker.

A urea channel from Bacillus cereus reveals a novel hexameric structure.

Urea is exploited as a nitrogen source by bacteria, and its breakdown products, ammonia and bicarbonate, are employed to counteract stomach acidity in pathogens such as Helicobacter pylori. Uptake in the latter is mediated by UreI, a UAC (urea amide channel) family member. In the present paper, we describe the structure and function of UACBc, a homologue from Bacillus cereus. The purified channel was found to be permeable not only to urea, but also to other small amides. CD and IR spectroscopy revealed a structure comprising mainly α-helices, oriented approximately perpendicular to the membrane. Consistent with this finding, site-directed fluorescent labelling indicated the presence of seven TM (transmembrane) helices, with a cytoplasmic C-terminus. In detergent, UACBc exists largely as a hexamer, as demonstrated by both cross-linking and size-exclusion chromatography. A 9 Å (1 Å=0.1 nm) resolution projection map obtained by cryo-electron microscopy of two-dimensional crystals shows that the six protomers are arranged in a planar hexameric ring. Each exhibits six density features attributable to TM helices, surrounding a putative central channel, while an additional helix is peripherally located. Bioinformatic analyses allowed individual TM regions to be tentatively assigned to the density features, with the resultant model enabling identification of residues likely to contribute to channel function.

Simple demographic, laboratory and chest radiograph variables can identify COVID-19 patients with pulmonary thromboembolism: a retrospective multicentre United Kingdom study.

OBJECTIVES: To (1) identify discriminatory demographic, laboratory and initial CXR findings; (2) explore correlation between D-dimer and radiographic severity scores; and (3) assess accuracy of published D-dimer thresholds to identify pulmonary thromboembolism (PTE) in COVID-19 patients. METHODS: Retrospective study including all COVID-19 patients admitted from 1st to 30th April 2020 meeting inclusion criteria from 25 (blinded) hospitals. Demographics, blood results, CXR and CTPA findings were compared between positive and negative PTE cohorts using uni- and multivariable logistic regression. Published D-dimer cut-offs were applied. RESULTS: 389 patients were included [median age 63; 237 males], of which 26.2% had a PTE. Significant univariable discriminators for PTE were peak D-dimer, sex, neutrophil count at the time of the D-dimer and at admission, abnormal CXR, and CXR zonal severity score. Only neutrophil count at peak D-dimer remained significant for predicting PTE on multivariable analysis (p = 0.008). When compared with the published literature, sensitivity for PTE were lower than those published at all cut-off values, however specificity at different cut-offs was variable. CONCLUSIONS: In this multicentre COVID-19 cohort, univariable admission factors that could indicate pulmonary thromboembolism were male sex, high neutrophil count and abnormal CXR with a greater CXR zonal severity score. The accuracy levels of published D-dimer thresholds were not reproducible in our population. ADVANCES IN KNOWLEDGE: This is a large multicentre study looking at the discriminatory value of simple variables to determine if a patient with COVID-19 has PTE or not, in addition to comparing D-dimer cut off values against published values.

The effects of climate change on outdoor recreation participation in the United States: Projections for the 21st century.

Climate change is expected to impact individuals' recreational choices, as changing temperatures and precipitation patterns influence participation in outdoor recreation and alternative activities. This paper empirically investigates the relationship between weather and outdoor recreation using nationally representative data from the contiguous United States. We find that across most outdoor recreational activities, participation is lowest on the coldest days (<35 degrees Fahrenheit) and highest at moderately high temperatures (80 to 90 degrees). Notable exceptions to this trend include water sports and snow and ice sports, for which participation peaks at the highest and lowest temperatures, respectively. If individuals continue to respond to temperature changes the same way that they have in the recent past, in a future climate that has fewer cool days and more moderate and hot days, our model anticipates net participation across all outdoor recreation activities will increase by 88 million trips annually at 1 degree Celsius of warming (CONUS) and up to 401 million trips at 6 degrees of warming, valued between $3.2 billion and $15.6 billion in consumer surplus annually (2010 population). The increase in trips is driven by participation in water sports; excluding water sports from future projections decreases the consumer surplus gains by approximately 75 percent across all modeled degrees of warming. If individuals in northern regions respond to temperature like people in southern regions currently do (a proxy for adaptation), total outdoor recreation trips will increase by an additional 17 percent compared to no adaptation at 6 degrees of warming. This benefit is generally not seen at lower degrees of warming.

Novel HALO® image analysis to determine cell phenotype in porous precision-templated scaffolds.

Image analysis platforms have gained increasing popularity in the last decade for the ability to automate and conduct high-throughput, multiplex, and quantitative analyses of a broad range of pathological tissues. However, imaging tissues with unique morphology or tissues containing implanted biomaterial scaffolds remain a challenge. Using HALO®, an image analysis platform specialized in quantitative tissue analysis, we have developed a novel method to determine multiple cell phenotypes in porous precision-templated scaffolds (PTS). PTS with uniform spherical pores between 30 and 40 µm in diameter have previously exhibited a specific immunomodulation of macrophages toward a pro-healing phenotype and an overall diminished foreign body response (FBR) compared to PTS with larger or smaller pore sizes. However, signaling pathways orchestrating this pro-healing in 40 µm PTS remain unclear. Here, we use HALO® to phenotype PTS resident cells and found a decrease in pro-inflammatory CD86 and an increase in pro-healing CD206 expression in 40 µm PTS compared to 100 µm PTS. To understand the mechanisms that drive these outcomes, we investigated the role of myeloid-differentiation-primary-response gene 88 (MyD88) in regulating the pro-healing phenomenon observed only in 40 µm PTS. When subcutaneously implanted in MyD88KO mice, 40 µm PTS reduced the expression of CD206, and the scaffold resident cells displayed an average larger nuclear size compared to 40 µm PTS implanted in mice expressing MyD88. Overall, this study demonstrates a novel image analysis method for phenotyping cells within PTS and identifies MyD88 as a critical mediator in the pore-size-dependent regenerative healing and host immune response to PTS.

The Asian American Vote in 2020: Indicators of Turnout and Vote Choice.

What were the indicators of voter turnout and presidential vote choice among Asian Americans in 2020? We argue that 2020 was a unique year in which race was salient for Asian Americans due to the rise of anti-Asian attitudes attributed to the COVID-19 pandemic and the opportunity to elect a vice presidential candidate of Asian descent. Because of this, racial considerations played a unique role that informed Asian American political participation and attitudes in this election. Using data from the 2020 Collaborative Multiracial Post-Election Survey, we identify the individual-level factors associated with turnout and presidential vote choice among Asian Americans. We find that stronger perceptions of racial discrimination were related to a higher likelihood of turnout and voting in support of the Democratic Party, especially among Asian immigrants relative to the native-born. This study offers new insight for when we can expect racial considerations to inform the politics of Asian Americans, who are the fastest growing racial group in the United States and therefore an increasingly important bloc of the electorate. Supplementary Information: The online version contains supplementary material available at 10.1007/s11109-022-09844-9.

Monocytes contribute to a pro-healing response in 40 µm diameter uniform-pore, precision-templated scaffolds.

Porous precision-templated scaffolds (PTS) with uniformly distributed 40 µm spherical pores have shown a remarkable ability in immunomodulating resident cells for tissue regeneration. While the pore size mediated pro-healing response observed only in 40 µm pore PTS has been attributed to selective macrophage polarization, monocyte recruitment and phenotype have largely been uncharacterized in regulating implant outcome. Here, we employ a double transgenic mouse model for myeloid characterization and a multifaceted phenotyping approach to quantify monocyte dynamics within subcutaneously implanted PTS. Within 40 µm PTS, myeloid cells were found to preferentially infiltrate into the scaffold. Additionally, macrophage receptor with collagenous structure (MARCO), an innate activation marker, was significantly upregulated within 40 µm PTS. When 40 µm PTS were implanted in monocyte-depleted mice, the transcription of MARCO was significantly decreased and an increase in pro-inflammatory inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNFα) were observed. Typical of a foreign body response (FBR), 100 µm PTS significantly upregulated pro-inflammatory iNOS, secreted higher amounts of TNFα, and displayed a pore size dependent morphology compared to 40 µm PTS. Overall, these results identify a pore size dependent modulation of circulating monocytes and implicates MARCO expression as a defining subset of monocytes that appears to be responsible for regulating a pro-healing host response.

Evaluating the use of semi-structured crowdsourced data to quantify inequitable access to urban biodiversity: A case study with eBird.

Credibly estimating social-ecological relationships requires data with broad coverage and fine geographic resolutions that are not typically available from standard ecological surveys. Open and unstructured data from crowdsourced platforms offer an opportunity for collecting large quantities of user-submitted ecological data. However, the representativeness of the areas sampled by these data portals is not well known. We investigate how data availability in eBird, one of the largest and most popular crowdsourced science platforms, correlates with race and income of census tracts in two cities: Boston, MA and Phoenix, AZ. We find that checklist submissions vary greatly across census tracts, with similar patterns within both metropolitan regions. In particular, census tracts with high income and high proportions of white residents are most likely to be represented in the data in both cities, which indicates selection bias in eBird coverage. Our results illustrate the non-representativeness of eBird data, and they also raise deeper questions about the validity of statistical inferences regarding disparities that can be drawn from such datasets. We discuss these challenges and illustrate how sample selection problems in unstructured or semi-structured crowdsourced data can lead to spurious conclusions regarding the relationships between race, income, and access to urban bird biodiversity. While crowdsourced data are indispensable and complementary to more traditional approaches for collecting ecological data, we conclude that unstructured or semi-structured data may not be well-suited for all lines of inquiry, particularly those requiring consistent data coverage, and should thus be handled with appropriate care.

The initial experience with the Embotrap III stent-retriever in a real world setting.

MATERIALS AND METHODS: We performed a retrospective review of our prospectively maintained database to identify all patients treated with the Embotrap 3 stent-retriever between January 2021 and January 2022. We recorded the baseline demographics, NIHSS, ASPECT score and clot characteristics, first pass and final eTICI scores, complications and 90 day mRS. RESULTS: One hundred and ten patients met the inclusion criteria, average age 69 ± 14 years, 50% were male (n = 55). The median NIHSS at presentation was 18 (range 3-30) and 58.2% received IV tPA prior to MT. The median ASPECT score on plain CT was 8 with average clot length 20.2 ± 14.8 mm (n = 93). The first pass effect (FPE) was seen in 41.8% of cases with modified FPE seen in 59.1%. A 24-hour CT scan (n = 97) showed median ASPECTs of 7. 43.8% of patients achieve mRS ≤ 2 at 90-day mRS (n = 64). CONCLUSION: The Embotrap 3 stent-retriever has a high rate of FPE and final recanalization in this real world cohort of patients.