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Neurons in primary visual cortex (V1) may not only signal current visual input but also relevant contextual information such as reward expectancy and the subject’s spatial position. Such contextual representations need not be restricted to V1 but could participate in a coherent mapping throughout sensory cortices. Here, we show that spiking activity coherently represents a location-specific mapping across auditory cortex (AC) and lateral, secondary visual cortex (V2L) of freely moving rats engaged in a sensory detection task on a figure-8 maze. Single-unit activity of both areas showed extensive similarities in terms of spatial distribution, reliability, and position coding. Importantly, reconstructions of subject position based on spiking activity displayed decoding errors that were correlated between areas. Additionally, we found that head direction, but not locomotor speed or head angular velocity, was an important determinant of activity in AC and V2L. By contrast, variables related to the sensory task cues or to trial correctness and reward were not markedly encoded in AC and V2L. We conclude that sensory cortices participate in coherent, multimodal representations of the subject’s sensory-specific location. These may provide a common reference frame for distributed cortical sensory and motor processes and may support crossmodal predictive processing.

Comparative studies of carpal tunnel release with ultrasound guidance (CTR-US) vs. mini-open CTR (mOCTR) are limited, prompting development of this randomized trial to compare efficacy and safety of these techniques. Patients were randomized (2:1) to CTR-US or mOCTR, treated by experienced hand surgeons (median previous cases: 12 CTR-US; 1000 mOCTR), and followed for 3 months. Among 149 randomized patients, 122 received CTR-US (n = 94) or mOCTR (n = 28). Mean incision length was 6 ± 2 mm in the wrist (CTR-US) vs. 22 ± 7 mm in the palm (mOCTR) (p < 0.001). Median time to return to daily activities (2 vs. 2 days; p = 0.81) and work (3 vs. 4 days; p = 0.61) were similar. Both groups reported statistically significant and clinically important improvements in Boston Carpal Tunnel Questionnaire Symptom Severity and Functional Status Scales, Numeric Pain Scale, and EuroQoL-5 Dimension 5-Level, with no statistical differences between groups. Freedom from wound sensitivity and pain favored CTR-US (61.1% vs. 17.9%; p < 0.001). Adverse event rates were low in each group (2.1% vs. 3.6%; p = 0.55). The efficacy and safety of CTR-US were comparable to mOCTR despite less previous surgical experience with CTR-US. The choice of CTR technique should be determined by shared decision-making between patient and physician. www.clinicaltrials.gov identifier is NCT05405218.

Social learning is a critical adaptation for dealing with different forms of variability. Uncertainty is a severe form of variability where the space of possible decisions or probabilities of associated outcomes are unknown. We identified four theoretically-important sources of uncertainty: temporal environmental variability, payoff ambiguity, selection-set size, and effective lifespan. When these combine, it is nearly impossible to fully learn about the environment. We develop an evolutionary agent-based model to test how each form of uncertainty affects the evolution of social learning. Agents perform one of several behaviors, modeled as a multi-armed bandit, to acquire payoffs. All agents learn about behavioral payoffs individually through an adaptive behavior-choice model that uses a softmax decision rule. Use of vertical and oblique payoff-biased social learning evolved to serve as a scaffold for adaptive individual learning—they are not opposite strategies. Different types of uncertainty had varying effects. Temporal environmental variability suppressed social learning, whereas larger selection-set size promoted social learning, even when the environment changed frequently. Payoff ambiguity and lifespan interacted with other uncertainty parameters. This study begins to explain how social learning can predominate despite highly variable real-world environments when effective individual learning helps individuals recover from learning outdated social information.

Private organizations that produce public goods often receive offers for funding from large donors who seek to influence the nature of the public goods produced. We consider a model in which the potential for large donor influence creates a commitment problem for the organization in the sense that, from an ex ante perspective, the organization sets the price for influence too low given the opportunity cost. Our analysis identifies determinants of the likelihood of large donor influence and assesses various mechanisms that can alleviate or exploit the commitment problem—greater transparency, organization leadership preferences and/or incentives, and targeted small donor campaigns. Finally, we assess how an option to walk back influential large donor contributions or an inability to commit to longer-term agreements with influential donors alters the implications of potential large donor influence. JEL Classifications: D64; L31.

Low back pain is a multidimensional disorder that can originate from a variety of pain generators, including the sacroiliac (SI) joint. Although the Oswestry Disability Index (ODI) is often used in SI joint treatment studies, the effects of the SI joint on functional disability are likely different from those of other low back pain generators. Thus, we developed the Denver SI Joint Questionnaire (DSIJQ) and performed validation testing in patients (n=24) with SI joint-specific pain at baseline, +2 weeks, and +6 months. Psychometric analyses included test-retest reliability, internal consistency, content validity, convergent criterion validity, divergent criterion validity, and responsiveness. The DSIJQ showed good test-retest reliability (intraclass correlation coefficient=0.87), internal consistency (Cronbach's alpha=0.842), content validity (r =0.89; P r =−0.33; P =.12). The DSIJQ was correlated with performance on two physical function tests: Timed Upand-Go ( r =0.53; P =.008) and 5 Minute Walk ( r =−0.52; P =.009). The DSIJQ showed better responsiveness than the ODI (standardized response mean and effect size, 1.14 and 1.45 for DSIJQ and 0.75 and 0.81 for ODI). Overall, the DSIJQ performed well on all psychometrics. Importantly, we validated the DSIJQ with patients' ability to complete two tests of physical functioning. Moreover, the DSIJQ was more sensitive to changes in SI joint disability than the ODI. These psychometrics suggest the DSIJQ is appropriate for evaluating SI joint disability and detecting changes in disability after targeted SI joint treatment. [ Orthopedics . 202x;4x(x):xx–xx.]

OBJECTIVE Oxytocin (OXT) secretion has been shown to be abnormally elevated in patients who develop syndrome of inappropriate secretion of antidiuretic hormone (SIADH)–related hyponatremia after transsphenoidal pituitary surgery (TPS). While OXT was previously reported to increase natriuresis in the kidney, a potential role for this hormone in postoperative sodium balance and dysnatremias has not been studied. The objective of this study was to analyze the correlation between patients’ urinary output of OXT and natremia and natriuresis after TPS. METHODS The authors measured and correlated the urinary output of OXT with natriuresis and natremia in 20 consecutive patients who underwent TPS. RESULTS The ratio of urinary secretion of OXT between days 1 and 4 showed a strong, significant correlation with patient natriuresis at day 7 after pituitary surgery. Concomitantly, patient natremia showed a moderate, inverted correlation with OXT secretion in the urine. CONCLUSIONS Together, these results show for the first time that urinary OXT secretion correlates with patient natriuresis and natremia after pituitary surgery. This observation suggests a notable role for this hormone in sodium balance.

Background: Accurately identifying cognitive changes in Mexican American (MA) adults using the Mini-Mental State Examination (MMSE) requires knowledge of population-based norms for the MMSE, a scale which has widespread use in research settings. Objective: To describe the distribution of MMSE scores in a large cohort of MA adults, assess the impact of MMSE requirements on their clinical trial eligibility, and explore which factors are most strongly associated with their MMSE scores. Methods: Visits between 2004–2021 in the Cameron County Hispanic Cohort were analyzed. Eligible participants were ≥18 years old and of Mexican descent. MMSE distributions before and after stratification by age and years of education (YOE) were assessed, as was the proportion of trial-aged (50–85– year-old) participants with MMSE

We describe three new genera and four new species of small, litter-dwelling millipedes from the states of Oregon and Washington, USA: Miniaria ramifera, n. gen., n. sp., Miniaria richarti, n. gen., n. sp., Tigraria oregonensis, n. gen., n. sp., and Kingaria prattensis, n. gen., n. sp. Some of the unusual characters of these species are discussed, including a new type of sensory array on the third tarsus of males and a newly observed mandibular gland.

We study short-term and medium-term changes in bank risk-taking as a result of supervision, and the associated real effects. For identification, we exploit the European Central Bank’s asset-quality review (AQR) in conjunction with security and credit registers. After the AQR announcement, reviewed banks reduce riskier securities and credit supply, with the greatest effect on riskiest securities. We find negative spillovers on asset prices and firm-level credit availability. Moreover, non-banks with higher exposure to reviewed banks acquire the shed risk. After the AQR compliance, reviewed banks reload riskier securities but not riskier credit, resulting in negative medium-term firm-level real effects. These effects are especially strong for firms with high ex-ante credit risk. Among these non-safe firms, even those with high ex-ante productivity experience negative real effects. Our findings suggest that banks’ liquid assets help them to mask risk from supervisors and risk adjustments banks make in response to supervision have persistent corporate real effects.

Amyloid-related imaging abnormalities (ARIA) is a term introduced in 2010 to encompass a spectrum of MRI findings observed in patients receiving investigational anti-amyloid beta (Aβ) immunotherapies for Alzheimer disease (AD). The entity can be broadly categorized into ARIA-E, characterized by edema and effusion, and ARIA-H, characterized by microhemorrhages and superficial siderosis. ARIA typically occurs early in the treatment course and has a higher incidence in patients who are apolipoprotein E ε4 allele carriers. ARIA-E has an additional dose dependence, with higher incidence in patients receiving higher doses of anti-Aβ immunotherapies. ARIA is often asymptomatic and self-resolving. The recognition of ARIA has implications for patient selection and monitoring for Aβ immunotherapies, and its development can potentially lead to a pause or discontinuation of therapy. The FDA's first approval of an Aβ-targeted mAb for AD treatment in 2021 will lead to such therapy's expanded use beyond the clinical trial setting and to radiologists more commonly encountering ARIA in clinical practice. This review explores the theorized pathophysiologic mechanisms for ARIA, describes the MRI findings and grading schemes for ARIA-E and AREA-H, and summarizes relevant Aβ immunotherapies. Through such knowledge, radiologists can optimally impact the management of patients receiving targeted AD therapies.

For approximately four decades, scientists have known of the existence of several undescribed species of Siren in the southeastern United States Coastal Plain. One of these species, S. reticulata, was recently described, but a small, seepage-dwelling species has remained undescribed until now. To resolve outstanding questions concerning the phylogeny of Siren, we collected sequence and morphometric data from specimens across the range of Siren. We found S. lacertina and S. reticulata to represent strongly supported monophyletic groups, with S. reticulata having a sister relationship to all other Siren. Additionally, we found five distinct mtDNA lineages within what has been recognized as S. intermedia. Siren lacertina and type-locality S. intermedia (lineage A) are sister mtDNA lineages, whereas S. intermedia lineages B and C show a high level of mitogenomic divergence from type-locality S. intermedia. Analyses of two scnDNA loci revealed that S. lacertina is monophyletic but nested with low positional support in a clade including the three S. intermedia mtDNA lineages. Further study is needed to determine whether S. intermedia lineages A, B, and C represent distinct species or incompletely sorted lineages. We restrict the range of S. intermedia to the region from the Escambia and Perdido river drainages of Florida and Alabama eastward through Virginia (the combined ranges of lineages A, B, and C). We also elevate S. i. nettingi (lineage E) to species status and include the larger S. i. texana form in that taxon, generating a species that occurs from the Mobile Bay drainages westward through the Mississippi Basin and southwest into northeastern Mexico. Lastly, we describe a new miniature species, S. sphagnicola, that ranges from the Florida Parishes of Louisiana eastward to the westernmost tributary creeks of Choctawhatchee Bay in the western Florida panhandle.

Providing method descriptions that are more detailed than currently available in typical peer reviewed journals has been identified as an actionable area for improvement. In the biochemical and cell biology space, this need has been met through the creation of new journals focused on detailed protocols and materials sourcing. However, this format is not well suited for capturing instrument validation, detailed imaging protocols, and extensive statistical analysis. Furthermore, the need for additional information must be counterbalanced by the additional time burden placed upon researchers who may be already overtasked. To address these competing issues, this white paper describes protocol templates for positron emission tomography (PET), X-ray computed tomography (CT), and magnetic resonance imaging (MRI) that can be leveraged by the broad community of quantitative imaging experts to write and self-publish protocols in protocols.io. Similar to the Structured Transparent Accessible Reproducible (STAR) or Journal of Visualized Experiments (JoVE) articles, authors are encouraged to publish peer reviewed papers and then to submit more detailed experimental protocols using this template to the online resource. Such protocols should be easy to use, readily accessible, readily searchable, considered open access, enable community feedback, editable, and citable by the author.

Minimal residual disease detection provides critical prognostic predictor of treatment outcome and is the standard of care for B lymphoblastic leukemia. Flow cytometry-based minimal residual disease detection is the most common test modality and has high sensitivity (0.01%) and a rapid turnaround time (24 hours). This article details the leukemia associated immunophenotype analysis approach for flow cytometry-based minimal residual disease detection used at St. Jude Children's Research Hospital and importance of using guide gates and back-gating.

Obstructive sleep apnea (OSA) is a common treatable condition with important health and societal consequences.We aimed to assess annual incidence and prevalence of clinically recognized and geographic clustering of OSA in Alberta, Canada using administrative health data case definitions.We used two administrative health databases in Alberta to identify ICD-9 and ICD-10 diagnostic codes for adults and children ≥ two years old diagnosed with OSA from 2003-2020. We defined OSA using an algorithm that was developed and validated in Alberta: at least three claims or one hospitalization within two years. We mapped residential postal code to 70 sub-regional health authorities (SRHAs). Crude, age group- and sex-specific incidence and prevalence, and age group- and sex-standardized rates were calculated for Alberta and for SRHAs. Spatial scan statistics identified clusters of SRHAs in which OSA cases were higher ("hot spots") or lower ("cold spots") than expected.Between 2003 and 2020, OSA prevalence increased from 0.14% to 4.59%. Annual incidence of OSA increased after 2013. Incidence and prevalence were higher in older adults, and higher in children aged 2-11 compared to 12-17 years. Cluster analysis revealed regional variation in OSA incidence and prevalence over time with no consistent pattern except for cold spots in one large metropolitan centre (Calgary).From 2003-2020 the incidence and prevalence of clinically recognized OSA increased but varied by geography. Administrative health data can be used to guide interventions aimed at improving health service delivery and quality of OSA care.

The publication of the American Academy of Pediatrics report on a “Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents with Obesity” has been met with considerable debate about the merits of taking a more aggressive treatment approach. Supporters of the new guidance argue that the time has come to treat childhood obesity with more intensive behavior therapy along with, as needed, weight loss medications and bariatric surgery. Detractors of the report believe that medicalizing this condition will lead to greater stigma and increase health disparities. Critics of the new guidance favor a “healthy at every size” approach. This editorial examines the reasoning behind these arguments. Given obesity is a complex issue that demands both clinical and societal solutions, this commentary advocates for multi-disciplinary cooperation and understanding in order to achieve an effective balance between prevention and treatment.

Background: Moderate-to-severe hemophilia B is treated with lifelong, continuous coagulation factor IX replacement to prevent bleeding. Gene therapy for hemophilia B aims to establish sustained factor IX activity, thereby protecting against bleeding without burdensome factor IX replacement. Methods: In this open-label, phase 3 study, after a lead-in period (≥6 months) of factor IX prophylaxis, we administered one infusion of adeno-associated virus 5 (AAV5) vector expressing the Padua factor IX variant (etranacogene dezaparvovec; 2×1013 genome copies per kilogram of body weight) to 54 men with hemophilia B (factor IX activity ≤2% of the normal value) regardless of preexisting AAV5 neutralizing antibodies. The primary end point was the annualized bleeding rate, evaluated in a noninferiority analysis comparing the rate during months 7 through 18 after etranacogene dezaparvovec treatment with the rate during the lead-in period. Noninferiority of etranacogene dezaparvovec was defined as an upper limit of the two-sided 95% Wald confidence interval of the annualized bleeding rate ratio that was less than the noninferiority margin of 1.8. Superiority, additional efficacy measures, and safety were also assessed. Results: The annualized bleeding rate decreased from 4.19 (95% confidence interval [CI], 3.22 to 5.45) during the lead-in period to 1.51 (95% CI, 0.81 to 2.82) during months 7 through 18 after treatment, for a rate ratio of 0.36 (95% Wald CI, 0.20 to 0.64; P

Anti-CRISPR proteins are very efficient for inhibiting CRISPR/Cas9-based genome editing tools in both herbaceous and woody plant species.

Relevant to co-clinical trials, the goal of this work was to assess repeatability, reproducibility, and bias of the apparent diffusion coefficient (ADC) for preclinical MRIs using standardized procedures for comparison to performance of clinical MRIs. A temperature-controlled phantom provided an absolute reference standard to measure spatial uniformity of these performance metrics. Seven institutions participated in the study, wherein diffusion-weighted imaging (DWI) data were acquired over multiple days on 10 preclinical scanners, from 3 vendors, at 6 field strengths. Centralized versus site-based analysis was compared to illustrate incremental variance due to processing workflow. At magnet isocenter, short-term (intra-exam) and long-term (multiday) repeatability were excellent at within-system coefficient of variance, wCV [±CI] = 0.73% [0.54%, 1.12%] and 1.26% [0.94%, 1.89%], respectively. The cross-system reproducibility coefficient, RDC [±CI] = 0.188 [0.129, 0.343] µm2/ms, corresponded to 17% [12%, 31%] relative to the reference standard. Absolute bias at isocenter was low (within 4%) for 8 of 10 systems, whereas two high-bias (>10%) scanners were primary contributors to the relatively high RDC. Significant additional variance (>2%) due to site-specific analysis was observed for 2 of 10 systems. Base-level technical bias, repeatability, reproducibility, and spatial uniformity patterns were consistent with human MRIs (scaled for bore size). Well-calibrated preclinical MRI systems are capable of highly repeatable and reproducible ADC measurements.

Computer-extracted tumour characteristics have been incorporated into medical imaging computer-aided diagnosis (CAD) algorithms for decades. With the advent of radiomics, an extension of CAD involving high-throughput computer-extracted quantitative characterization of healthy or pathological structures and processes as captured by medical imaging, interest in such computer-extracted measurements has increased substantially. However, despite the thousands of radiomic studies, the number of settings in which radiomics has been successfully translated into a clinically useful tool or has obtained FDA clearance is comparatively small. This relative dearth might be attributable to factors such as the varying imaging and radiomic feature extraction protocols used from study to study, the numerous potential pitfalls in the analysis of radiomic data, and the lack of studies showing that acting upon a radiomic-based tool leads to a favourable benefit-risk balance for the patient. Several guidelines on specific aspects of radiomic data acquisition and analysis are already available, although a similar roadmap for the overall process of translating radiomics into tools that can be used in clinical care is needed. Herein, we provide 16 criteria for the effective execution of this process in the hopes that they will guide the development of more clinically useful radiomic tests in the future.

The language we use in our scientific communications can either empower or stigmatize the people we study and care for. Clinical Infectious Diseases is committed to prioritizing the use of inclusive, nonstigmatizing language in published manuscripts. We hereby call upon submitting authors, reviewers, and editors to do the same.