Escape from the second dimension: A topological distinction between edge and screw dislocations.

Volterra's definition of dislocations in crystals geometrically distinguishes edge and screw defects according to whether the Burgers vector is perpendicular or parallel to the defect. A homotopy-theoretic analysis of dislocations as topological defects fails to differentiate edge and screw. Here we bridge the gap between the geometric and topological descriptions by demonstrating that there is a topological difference between screw and edge defects. Our construction distinguishes edge and screw based on the disclination-line pairs at the core of smectic dislocations. By exploiting the connection between topology and geometry in the form of Gaussian curvature, this analysis results in an invariant for dislocations in the saddle-splay vector. This construction can be generalized to crystals with triply periodic order.

The importance of accounting method and sampling depth to estimate changes in soil carbon stocks.

BACKGROUND: As interest in the voluntary soil carbon market surges, carbon registries have been developing new soil carbon measurement, reporting, and verification (MRV) protocols. These protocols are inconsistent in their approaches to measuring soil organic carbon (SOC). Two areas of concern include the type of SOC stock accounting method (fixed-depth (FD) vs. equivalent soil mass (ESM)) and sampling depth requirement. Despite evidence that fixed-depth measurements can result in error because of changes in soil bulk density and that sampling to 30 cm neglects a significant portion of the soil profile's SOC stock, most MRV protocols do not specify which sampling method to use and only require sampling to 30 cm. Using data from UC Davis's Century Experiment ("Century") and UW Madison's Wisconsin Integrated Cropping Systems Trial (WICST), we quantify differences in SOC stock changes estimated by FD and ESM over 20 years, investigate how sampling at-depth (> 30 cm) affects SOC stock change estimates, and estimate how crediting outcomes taking an empirical sampling-only crediting approach differ when stocks are calculated using ESM or FD at different depths. RESULTS: We find that FD and ESM estimates of stock change can differ by over 100 percent and that, as expected, much of this difference is associated with changes in bulk density in surface soils (e.g., r = 0.90 for Century maize treatments). This led to substantial differences in crediting outcomes between ESM and FD-based stocks, although many treatments did not receive credits due to declines in SOC stocks over time. While increased variability of soils at depth makes it challenging to accurately quantify stocks across the profile, sampling to 60 cm can capture changes in bulk density, potential SOC redistribution, and a larger proportion of the overall SOC stock. CONCLUSIONS: ESM accounting and sampling to 60 cm (using multiple depth increments) should be considered best practice when quantifying change in SOC stocks in annual, row crop agroecosystems. For carbon markets, the cost of achieving an accurate estimate of SOC stocks that reflect management impacts on soils at-depth should be reflected in the price of carbon credits.

Nephrotic Syndrome in a Child With NPHS2 Mutation.

Steroid resistant nephrotic syndrome (SRNS) accounts for 30% of all cases of nephrotic syndrome (NS) in children and frequently leads to end stage kidney disease (ESKD). About 30% of children with SRNS demonstrate causative mutations in podocyte- associated genes. Early identification of genetic forms of SRNS is critical to avoid potentially harmful immunosuppressive therapy. A 2-year-old male patient with NS and no family history of renal disease did not respond to 4-week steroid treatment. Kidney biopsy demonstrated mesangial proliferative glomerulopathy with basement membrane dysmorphism. Tacrolimus and Lisinopril were added to therapy pending results of genetic testing. Kidney Gene panel showed a NPHS2 c.413G>A (p.Arg138Gln) homozygous pathogenic variant. This missense variant is considered a common pathogenic founder mutation in European populations. A diagnosis of autosomal-recessive form of nonsyndromic SRNS due to NPHS2 causative variant was made. Immunosuppresive therapy was stopped, Lizinopril dose was increased and weekly infusions of Albumin/furosemide were initiated to manage edema. This case demonstrates that early genetic testing in children with SRNS avoids prolonged potentially harmful immunosuppressive therapy, allows for timely genetic family counseling, and allows earlier consideration for future living related donor kidney transplantation.

Patient-reported frailty phenotype (PRFP) vs. International Myeloma Working Group frailty index (IMWG FI) proxy: A comparison between two approaches to measuring frailty.

INTRODUCTION: Frailty assessments may help to identify patients at highest risk for treatment-related toxicity, early treatment discontinuation due to toxicity, and death in Multiple Myeloma. We aimed to compare the patient-reported frailty phenotype (PRFP) and a modified version of the International Myeloma Working Group frailty index (IMWG FI) in terms of their strengths, limitations, and classification of frailty in a cohort of patients with relapsed/refractory multiple myeloma (RRMM). MATERIALS AND METHODS: Data were pooled from six RRMM Phase 3 randomized clinical trials submitted to the Food and Drug Administration for regulatory review between 2010 and 2021. Patients were classified as fit, intermediate fit/pre-frail, or frail using both PRFP and the IMWG FI proxy. Agreement between the two approaches in classification of patient frailty was assessed using weighted Cohen's kappa. A contingency table and Venn diagram were generated to analyze overlap in categorization of patient frailty across the different severity groups. Descriptive statistics were used to summarize and compare the clinical and demographic characteristics of patients categorized as frail by PRFP vs. IMWG FI proxy. RESULTS: Of the 2,750 patients included in this analysis, IMWG FI proxy classified 16.4% (452) patients as frail, 28.1% (772) as intermediate fit/pre-frail, and 55.5% (1,526) as fit. Meanwhile, PRFP classified 21.7% (597) of patients as frail, 24.5% (675) as intermediate fit/pre-frail, and 53.8% (1478) as fit. Fair agreement was observed between PRFP and IMWG FI proxy (weighted Cohen's Kappa = 0.34 [0.31-0.37]). On average, patients who were categorized as frail by IMWG FI proxy were older and had higher Charlson Comorbidity Index scores than patients classified as frail by PRFP. In contrast, patients who were classified as frail by PRFP had worse EORTC QLQ-C30 Physical Functioning subscale summary scores as compared to patients in the IMWG FI proxy frail group (median score of 40 vs. 47 out of 100). DISCUSSION: Our analysis found fair concordance between IMWG FI proxy and PRFP. This demonstrates that while both frailty models measure the same underlying construct, the variables that constitute each approach may result in differing frailty categorizations for the same patient. Further prospective studies are needed to establish and compare the predictive and prognostic abilities of the different frailty indices in MM.

Geometry of focal conics in sessile cholesteric droplets.

Focal conic domains are defects characteristic of layered liquid crystal phases. Their association can build flowers where petals are the ellipses of the Dupin cyclides involved in these defects. We report here the observation of focal conic flowers in cholesteric droplets sessile on a glass surface and surrounded by glycerol. The observation of the droplets in different directions helps to solve the three dimensional architecture of the flower. The effects of the droplet size and of the pitch value are also reported.

On the Proper Treatment of Dynamics in Cognitive Science.

This essay examines the relevance of dynamical ideas for cognitive science. On its own, the mere mathematical idea of a dynamical system is too weak to serve as a scientific theory of anything, and dynamical approaches within cognitive science are too rich and varied to be subsumed under a single "dynamical hypothesis." Instead, after first attempting to dissect the different notions of "dynamics" and "cognition" at play, a more specific theoretical framework for cognitive science broadly construed is sketched. This framework draws upon not only dynamical ideas, but also such contemporaneous perspectives as situatedness, embodiment, ecological psychology, enaction, neuroethology/neuroscience, artificial life, and biogenic approaches. The paper ends with some methodological suggestions for pursuing this theoretical framework.

What promotes smectic order: Applying mean-field theory to the ends.

Not every particle that forms a nematic liquid crystal makes a smectic. The particle tip is critical for this behavior. Ellipsoids do not make a smectic, but spherocylinders do. Similarly, only those N-CB alkylcyanobiphenyls with sufficiently long (N≥8 carbons) alkane tails form smectics. We understand the role of the particle tip in the smectic transition by means of a simple two-dimensional model. We model spherocylinders by "boubas" with rounded tips, and ellipsoids by "kikis" with pointed tips. The N-CB molecules are modeled by a small body with a polymer tail. We find that rounded tips and longer polymer tails lead to a smectic at lower densities by making the space between layers less accessible, destabilizing the nematic.

Current Utilization of Electron Microscopy in the Pediatric Pathology Setting: A Survey by the SPP Practice Committee.

BACKGROUND: Electron microscopy (EM), once an important component in diagnosing pediatric diseases, has experienced a decline in its use. To assess the impact of this, pediatric pathology practices were surveyed regarding EM services. METHODS: The Society of Pediatric Pathology Practice Committee surveyed 113 society members from 74 hospitals. Settings included 36 academic tertiary, 32 free-standing children's, and 6 community hospitals. RESULTS: Over 60% maintained in-house EM services and had more than 2 pathologists interpreting EM while reporting a shortage of EM technologists. Freestanding children's hospitals had the most specimens (100-200 per year) and more diverse specimen types. Hospitals with fewer than 50 yearly specimens often used reference laboratories. Seventeen had terminated all in-house EM services. Challenges included decreasing caseloads due to alternative diagnostic methods, high operating costs, and shortages of EM technologists and EM-proficient pathologists. Kidney, liver, cilia, heart, and muscle biopsies most often required EM. Lung/bronchoalveolar lavage, tumor, skin, gastrointestinal, nerve, platelet, and autopsy samples less commonly needed EM. CONCLUSIONS: The survey revealed challenges in maintaining EM services but demonstrated its sustained value in pediatric pathology. Pediatric pathologists may need to address the centralization of services and training to preserve EM diagnostic proficiency among pathologists who perform ultrastructural interpretations.

What Patients and Caregivers Experience When They Receive Palliative Care: A Study Eliciting Metaphors That Could Shape Public Messaging.

Many patients who could benefit from Palliative Care do not receive services because of lack of awareness or misconceptions. This high level of public unfamiliarity combined with inaccurate beliefs equating Palliative Care with dying calls for public messaging designed to increase public familiarity and correct misconceptions. A barrier to widespread public messaging, however, is the scarcity of messages developed with empirical research in public perceptions of the lived experience of receiving palliative care. In this report, we describe qualitative research aimed at identifying the "deep metaphors" associated with palliative care, to provide an empirical foundation for further creative work. We interviewed 8 patients receiving palliative care and 8 caregivers using a qualitative method, Zaltman Metaphor Elicitation Technique, that is specially designed to reveal unconscious metaphors and socially shared associations that participants held about experiencing palliative care. Study participants likened the onset of serious illness as a massive disruption resulting in stunning losses with far-reaching consequences. What serious illness "took away" from them was a sense of certainty about where their lives were going, and these participants described experiencing (1) shame and embarrassment about what was happening to them; (2) a sense that no one was listening to them; (3) feeling lost and uncertain about what to do, feeling stuck; and (4) losing parts of their identity to illness. What they felt in need of, to counter what had been taken away, was (1) validation for what they were going through; (2) agency to determine their own quality of life and have input into their care; (3) guidance to access a network of resources; and (4) regeneration of their self-worth, resulting in a new version of their identity. This research provides guidance for message developers on frames, language, and visuals for future campaigns designed to create public interest in palliative care.

Expression of Concern: Colossal Density-Driven Resistance Response in the Negative Charge Transfer Insulator MnS_{2} [Phys. Rev. Lett. 127, 016401 (2021)].

This corrects the article DOI: 10.1103/PhysRevLett.127.016401.

Measuring Frailty Using Patient-Reported Outcomes (PRO) Data: A Feasibility Study in Patients with Multiple Myeloma.

PURPOSE: The objective of this retrospective study was to determine the feasibility of measuring frailty using patient responses to relevant EORTC QLQ-C30 items as proxy criteria for the Fried Frailty Phenotype, in a cohort of patients with Relapsed/Refractory Multiple Myeloma (RRMM). METHODS: Data were pooled from nine Phase III randomized clinical trials submitted to the FDA for regulatory review between 2010 and 2021, for the treatment of RRMM. Baseline EORTC QLQ-C30 responses were used to derive a patient-reported frailty phenotype (PRFP), based on the Fried definition of frailty. PRFP was assessed for internal consistency reliability, structural validity, and known groups validity. RESULTS: This study demonstrated the feasibility of adapting patient responses to relevant EORTC QLQ-C30 items to serve as proxy Fried frailty criteria. Selected items were well correlated with one another and PRFP as a whole demonstrated adequate internal consistency reliability and structural validity. Known groups analysis demonstrated that PRFP could be used to detect distinct comorbidity levels and distinguish between different functional profiles, with frail patients reporting more difficulty in walking about, washing/dressing, and doing usual activities, as compared to their pre-frail and fit counterparts. Among the 4928 patients included in this study, PRFP classified 2729 (55.4%) patients as fit, 1209 (24.5%) as pre-frail, and 990 (20.1%) as frail. CONCLUSION: Constructing a frailty scale from existing PRO items commonly collected in cancer trials may be a patient-centric and practical approach to measuring frailty. Additional psychometric evaluation and research is warranted to further explore the utility of such an approach.

The theoretical foundations of enaction: Precariousness.

Enaction is an increasingly influential approach to cognition that grew out of Maturana and Varela's earlier work on autopoiesis and the biology of cognition. As with any relatively new scientific discipline, the enactive approach would benefit greatly from a careful analysis of its theoretical foundations. Here we initiate such an analysis for one of the core concepts of enaction, precariousness. Specifically, we consider three types of fragility: systemic, processual and thermodynamic. Using a glider in the Game of Life as a toy model, we illustrate each of these fragilities and examine the relationships between them. We also argue that each type of fragility is characterized by which aspects of a system are hardwired into its definition from the outset and which aspects are emergent and hence vulnerable to disintegration without ongoing maintenance.

Phthalates cause a low-renin phenotype commonly found in premature infants with idiopathic neonatal hypertension.

Since the 1970s, when the initial reports of neonatal hypertension related to renal artery thromboembolism were published, other secondary causes of neonatal hypertension have been reported. Those infants with no identifiable cause of hypertension were labeled with a variety of terms. Herein, we describe such infants as having idiopathic neonatal hypertension (INH). Most, but not all, of these hypertensive infants were noted to have bronchopulmonary dysplasia (BPD). More recently, reports described common clinical characteristics seen in INH patients, whether or not they had BPD. This phenotype includes low plasma renin activity, presentation near 40 weeks postmenstrual age, and a favorable response to treatment with spironolactone. A small prospective study in INH patents showed evidence of mineralocorticoid receptor activation due to inhibition of 11ß-HSD2, the enzyme that converts cortisol to the less potent mineralocorticoid-cortisone. Meanwhile, phthalate metabolites have been shown to inhibit 11ß-HSD2 in human microsomes. Premature infants can come in contact with exceptionally large phthalate exposures, especially those infants with BPD. This work describes a common low-renin phenotype, commonly seen in patients categorized as having INH. Further, we review the evidence that hypertension in INH patients with the low-renin phenotype may be mediated by phthalate-associated inhibition of 11ß-HSD2. Lastly, we review the implications of these findings regarding identification, treatment, and prevention of the low-renin hypertension phenotype seen in premature infants categorized as having INH.

Natural Shaping of Acellular Dermal Matrices for Implant-Based Breast Reconstruction via Expansile Kirigami.

To complete a successful and aesthetic breast reconstruction for breast cancer survivors, tissue reinforcing acellular dermal matrices (ADMs) are widely utilized to create slings/pockets to keep breast implants or autologous tissue transfer secured against the chest wall in the desired location. However, ADM sheets are 2D and cannot completely cover the entire implant without wrinkles. Here, guided by finite element modeling, a kirigami strategy is presented to cut the ADM sheets with locally and precisely controlled stretchability, curvature, and elasticity. Upon expansion, a single kirigami ADM sheet can conformably wrap the implant regardless of the shape and size, forming a natural teardrop shape; contour cuts prescribe the topographical height and fractal cuts in the center ensures horizontal expandability and thus conformability. This kirigami ADM can provide support to the reconstructed breast in the desired regions, potentially offering optimal outcomes and patient-specific reconstruction, while minimizing operative time and cost.

Security breach: peripheral nerves provide unrestricted access for toxin delivery into the central nervous system.

We explore the hypothesis that a potential explanation for the initiation of motor neuron disease is an unappreciated vulnerability in central nervous system defense, the direct delivery of neurotoxins into motor neurons via peripheral nerve retrograde transport. This further suggests a mechanism for focal initiation of neuro-degenerative diseases in general, with subsequent spread by network degeneration as suggested by the Frost-Diamond hypothesis. We propose this vulnerability may be a byproduct of vertebrate evolution in a benign aquatic environment, where external surfaces were not exposed to concentrated neurotoxins.

Callogobius williamsi, a new species of goby (Teleostei: Gobiidae) from the Marquesas Islands, with notes on the status of all nominal Callogobius species.

Callogobius williamsi new species is described from the 32.9 mm SL holotype and 29 paratypes (6.932.5 mm SL) from the Marquesas Islands, South Pacific Ocean. Callogobius williamsi is distinguished from all other known Callogobius species by the following combination of characters: scales mostly cycloid, ctenoid scales, if present, restricted to the mid-lateral caudal peduncle, 2326 (mode 25) scales in lateral series, preopercular papillae row (Row 20) absent, and the interorbital canal with pores B, D, and F present. Callogobius williamsi belongs to a group of 23 nominal species (the hasseltii group) that are hypothesized to be monophyletic based on the shared presence of narrow and closely spaced dorsal processes of the cleithrum and an elongate caudal fin (greater than head length in specimens over 20 mm SL). Following the species description is a discussion of the status of all nominal species of Callogobius including a table that provides provisional status for all species correctly assigned to the genus.

Ratchetlike motion of helical bilayers induced by boundary constraints.

We show that application of boundary constraints generates unusual folding behaviors in responsive (swellable) helical bilayer strips. Unlike the smooth folding trajectories typical of free helical bilayers, the boundary-constrained bilayers exhibit intermittent folding behaviors characterized by rapid, steplike movements. We experimentally study bilayer strips as they swell and fold, and we propose a simple model to explain the emergence of ratchetlike behavior. Experiments and model predictions are then compared to simulations, which enable calculation of elastic energy during swelling. We investigate the dependence of this steplike behavior as a function of elastic boundary condition strength, strip length, and strip shape; interestingly, "V-shape" strips with the same boundary conditions fold smoothly.