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Purpose: Removal of clinically benign eyelid margin lesions is frequently desired for cosmetic concerns. Although surgical excision remains the standard therapy for such lesions, it carries the risk of unfavorable outcomes. Hence, this study aimed to evaluate a more aesthetic technique entailing a posterior lamellar wedge resection of lower eyelid margin lesions through an infraciliary incision. Methods: A retrospective review of patients who underwent posterior lamellar wedge resection for benign lower eyelid margin lesions between May 2017 and June 2022 was performed. Patient satisfaction using the visual analog score (VAS) and cosmetic outcomes using the Strasser score. Results: Forty-two patients met the inclusion criteria (61.9% female, mean age: 46.8 years). Nevus was the most frequent histologic diagnosis (57.1%). Furthermore, 66.7% of lesions extended to the back of the lid margin. The mean defect size was 5.8 mm (range: 3.5-8 mm). The mean follow-up interval was 24.1 months (range: 6-60 months). Thirty-two (76.2%) eyelids had scores indicating an excellent result, and 10 (23.8%) patients had a good result. The mean patient satisfaction VAS score for the eyelid appearance was 96 (range: 70-100). There were no cases of recurrence of resected lesions. No further surgery was performed on the operated eyelid for any reason during the follow-up period. Conclusion: Posterior lamellar wedge resection for lower eyelid margin lesions was associated with excellent cosmetic outcomes, high patient satisfaction, and minimal adverse events. Keywords: Eyelid margin lesion, infraciliary incision, lower eyelid, posterior wedge resection, Author(s): Mostafa M Diab (corresponding author) [1]; Richard C Allen [2]; Ahmed A Ismail [1]; Ahmed T S Saif [1] Lower eyelid margin lesions are frequently encountered in everyday ophthalmic [...]

Having been in business with his brother Simon for several years as the independent 8-bit developer and publisher Software Invasion, a seismic change came about at the end of the [...]

In the late-Eighties and early Nineties, Anthony Taglione and Peter James collaborated on successful fantasy RPGs Bloodwych and Legend, but computer hardware and software was moving on at a rapid [...]

TABLE OF CONTENTS I. CONDITIONAL RELEASE AS A FORM OF OUTPATIENT COMMITMENT A. Policies and Recommendations for Outpatient Commitment B. State Laws Governing Conditional Release from Involuntary Psychiatric Hospitalization II. [...], This article takes up the question of how the right to refuse treatment operates in the context of conditional release from inpatient psychiatric commitment. Part One explores the practice of conditional release from inpatient psychiatric care as a form of outpatient commitment and describes the range of substantive and procedural approaches that are used to structure these step-down arrangements. Part Two then takes up the legal and policy questions associated with the right to grant or withhold consent to medication in the context of psychiatric treatment. Part Three concludes by considering how the doctrines described in Part Two map onto the practices set out in Part One and offers some suggestions for reconciling the competing interests at play.

Over the past decade or so, corporate reporting has broadened to cover issues not addressed in quarterly or annual GAAP financial reports. At present, such reporting, often called Corporate Sustainability [...]

TABLE OF CONTENTS I. Introduction 580 II. The Need for a Rule Barring Retroactive Disallowance 584 III. Relevant Court and Board Precedent 588 A. The 1971 Court of Claims Decision [...]

Contents I. Introduction II. Opioids A. The Chemistry of Opioids B. Marketing Practices Distributors and Retail Pharmacies C. The Current Opioid Addiction Epidemic III. Litigation Prior to 2014 IV. The [...]

Objective: To evaluate the quality of a multiyear linkage between the Colorado all-payer claims database (APCD) and the Colorado Central Cancer Registry. Data sources: Secondary 2012-2017 data from the APCD and the Colorado Cancer Registry. Study design: Descriptive analysis of the proportion of cases captured by the linkage in relation to the cases reported by the registry. Data collection/extraction methods: We used probabilistic linkage to combine records from both data sources for all patients diagnosed with cancer. Results: We successfully linked 93% of the 146,884 patients in the registry. Approximately 63% of linked patients were perfect matches on five identifiers. Of partial matches, 81.6% were matched on four identifiers with missing or partial Social Security Numbers. The linkage rate was lower for uninsured patients at diagnosis (74.7%) or patients with private plans (89.4%) but close to 100% for Medicare and Medicaid enrollees. Most of the 29% of patients who did not have claims at the time of diagnosis were covered by private plans that may not submit claims. Conclusions: APCD-registry linkages are a promising source of data to conduct population-based research from multiple payers. However, not all payers submit claims, and the quality of the data may vary by state. KEYWORDS all-payer claims databases, cancer, linkage, longitudinal, registry What is known on this topic * Health services research on cancer care and outcomes has benefited from linkages between claims databases and cancer registries, but these linkages are limited to a single payer, health system, or population. * Many states have developed all-payer claims databases, but each state has different rules regarding claims submission and not all payers are required to submit claims. * The quality of all-payer claims databases for cancer health services research is unknown. What this study adds * We linked most patients (93.0%) in the Colorado Cancer Registry with the Colorado all-payer claims databases, with high linkage rates of 98.6% for Medicare and 99.2% for Medicaid, and similar linkages rates by race and urban/rural residence (89.3%-94.8%). * Although we were able to link 93% of patients in the registry, nearly 30% of patients did not have claims at the time of diagnosis, either due to uninsurance or coverage from private plans that do not submit claims. * Even though nearly 30% of linked patients did not have claims data at the time of diagnosis, claims available in the linkage after diagnosis could be valuable in some study designs (e.g., survivorship studies) and baseline characteristics for these patients are available from the registry., 1 | INTRODUCTION Cancer health services research has benefited from the availability of claims data linked to cancer registry data; the most well-known example is Surveillance, Epidemiology, and End Results [...]

The brain helps us survive by forming internal representations of the external world1,2. Excitatory cortical neurons are often precisely tuned to specific external stimuli3,4. However, inhibitory neurons, such as parvalbumin-positive (PV) interneurons, are generally less selective5. PV interneurons differ from excitatory neurons in their neurotransmitter receptor subtypes, including AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs)6,7. Excitatory neurons express calcium-impermeable AMPARs that contain the GluA2 subunit (encoded by GRIA2), whereas PV interneurons express receptors that lack the GluA2 subunit and are calcium-permeable (CP-AMPARs). Here we demonstrate a causal relationship between CP-AMPAR expression and the low feature selectivity of PV interneurons. We find low expression stoichiometry of GRIA2mRNA relative to other subunits in PV interneurons that is conserved across ferrets, rodents, marmosets and humans, and causes abundant CP-AMPAR expression. Replacing CP-AMPARs in PV interneurons with calcium-impermeable AMPARs increased their orientation selectivity in the visual cortex. Manipulations to induce sparse CP-AMPAR expression demonstrated that this increase was cell-autonomous and could occur with changes beyond development. Notably, excitatory–PV interneuron connectivity rates and unitary synaptic strength were unaltered by CP-AMPAR removal, which suggested that the selectivity of PV interneurons can be altered without markedly changing connectivity. In Gria2-knockout mice, in which all AMPARs are calcium-permeable, excitatory neurons showed significantly degraded orientation selectivity, which suggested that CP-AMPARs are sufficient to drive lower selectivity regardless of cell type. Moreover, hippocampal PV interneurons, which usually exhibit low spatial tuning, became more spatially selective after removing CP-AMPARs, which indicated that CP-AMPARs suppress the feature selectivity of PV interneurons independent of modality. These results reveal a new role of CP-AMPARs in maintaining low-selectivity sensory representation in PV interneurons and implicate a conserved molecular mechanism that distinguishes this cell type in the neocortex.

Objective: The severity of atrial fibrillation (AF) can be assessed from intra-operative epicardial measurements (high-resolution electrograms), using metrics such as conduction block (CB) and continuous conduction delay and block (cCDCB). These features capture differences in conduction velocity and wavefront propagation, but ignore complementary properties such as the morphology of the action potentials. In this work, we focus on such complementary properties, and derive features to detect variations in the atrial potential waveforms. Methods: We show that the spatial variation of atrial potential morphology during a single beat may be described by changes in the singular values of the epicardial measurement matrix. The method is non-parametric and requires little preprocessing. A corresponding singular value map points at areas subject to fractionation and block. Further, we developed an experiment where we simultaneously measure electrograms (EGMs) and a multi-lead ECG. Results: The captured data showed that the normalized singular values of the heartbeats during AF are higher than during SR, and that this difference is more pronounced for the (non-invasive) ECG data than for the EGM data, if the electrodes are positioned at favorable locations. Conclusion: Overall, the singular value-based features are a useful indicator to detect and evaluate AF. Significance: The proposed method might be beneficial for identifying electropathological regions in the tissue without estimating the local activation time.

Minnesota acute graft versus host disease (AGVHD) risk score is a validated tool to stratify newly-diagnosed patients into standard-risk (SR) and high-risk (HR) groups with ~85% having SR AGVHD. We aimed to identify factors for further risk-stratification within Minnesota SR patients. A single-center, retrospective analysis of consecutive patients between 1/2010 and 12/2014 was performed. Patients who developed AGVHD within 100 days and treated with systemic corticosteroids were included (N= 416), 356 (86%) of which were Minnesota SR and 60 (14%) had HR AGVHD. Isolated upper gastrointestinal (GI) AGVHD patients had significantly better day 28 and 56 CR/PR rates (90% vs. 72%, p= 0.004) and (83% vs 66%, p= 0.01), respectively, and lower 1-year non-relapse mortality (NRM; 10% vs. 22%; HR 0.4, p= 0.03). Lower GI AGVHD had less favorable outcomes with 1-year NRM of 40% (HR 2.1, p= 0.001), although CR/PR rates were not statistically different. In multivariate analysis, lower GI involvement (HR 2.6, p< 0.001), age ≥ 50 (HR 2.9, p< 0.001) and HCT-CI > 3 (HR 2.1, p= 0.002) predicted for 1-year NRM. Heterogeneity within Minnesota SR patients requires consideration in clinical trials, as distinct outcomes are observed in those with isolated upper GI and lower GI AGVHD, highlighting the importance of stratification in clinical trial design.

The 78-kDa glucose-regulated protein (GRP78) expressed on the cell surface (csGRP78) has been reported to regulate tissue factor (TF) procoagulant activity (PCA) in lesion-resident endothelial cells (ECs), which is further enhanced by circulating anti-GRP78 autoantibodies that bind to the Leu98-Leu115epitope in GRP78.

Native lipid bilayer mimetics, including those that use amphiphilic polymers, are important for the effective study of membrane-bound peptides and proteins. Copolymers of vinyl ether monomers and maleic anhydride were developed with controlled molecular weights and hydrophobicity through reversible addition–fragmentation chain-transfer polymerization. After polymerization, the maleic anhydride units can be hydrolyzed, giving dicarboxylates. The vinyl ether and maleic anhydride copolymerized in a close to alternating manner, giving essentially alternating hydrophilic maleic acid units and hydrophobic vinyl ether units along the backbone after hydrolysis. The vinyl ether monomers and maleic acid polymers self-assembled with lipids, giving vinyl ether maleic acid lipid particles (VEMALPs) with tunable sizes controlled by either the vinyl ether hydrophobicity or the polymer molecular weight. These VEMALPs were able to support membrane-bound proteins and peptides, creating a new class of lipid bilayer mimetics.

The propensity of a surface to nucleate ice or bind to ice is governed by its ice-philicity─its relative preference for ice over liquid water. However, the relationship between the features of a surface and its ice-philicity is not well understood, and for surfaces with chemical or topographical heterogeneity, such as proteins, their ice-philicity is not even well-defined. In the analogous problem of surface hydrophobicity, it has been shown that hydrophobic surfaces display enhanced low water-density (vapor-like) fluctuations in their vicinity. To interrogate whether enhanced ice-like fluctuations are similarly observed near ice-philic surfaces, here we use molecular simulations and enhanced sampling techniques. Using a family of model surfaces for which the wetting coefficient, k, has previously been characterized, we show that the free energy of observing rare interfacial ice-density fluctuations decreases monotonically with increasing k. By utilizing this connection, we investigate a set of fcc systems and find that the (110) surface is more ice-philic than the (111) or (100) surfaces. By additionally analyzing the structure of interfacial ice, we find that all surfaces prefer to bind to the basal plane of ice, and the topographical complementarity of the (110) surface to the basal plane explains its higher ice-philicity. Using enhanced interfacial ice-like fluctuations as a measure of surface ice-philicity, we then characterize the ice-philicity of chemically heterogeneous and topologically complex systems. In particular, we study the spruce budworm antifreeze protein (sbwAFP), which binds to ice using a known ice-binding site (IBS) and resists engulfment using nonbinding sites of the protein (NBSs). We find that the IBS displays enhanced interfacial ice-density fluctuations and is therefore more ice-philic than the two NBSs studied. We also find the two NBSs are similarly ice-phobic. By establishing a connection between interfacial ice-like fluctuations and surface ice-philicity, our findings thus provide a way to characterize the ice-philicity of heterogeneous surfaces.

ABSTRACTOphiostoma haidanensisis described as a new species of the Ophiostoma piceaecomplex isolated from yellow-cedar (Callitropsis nootkatensis(D. Don) Oerst. ex D.P. Little) sapwood in the Haida Gwaii island archipelago and the North Coast of British Columbia, Canada. The fungus is characterized by the production of a typical sporothrix-like asexual morph but is distinguished morphologically from other members of the O. piceaespecies complex by its large, multiseptate primary conidia. Phylogenetic analysis of DNA sequences from the nuc rDNA internal transcribed spacer region ITS1-5.8S-ITS2 (ITS) and the β-tubulin (BTUB) and translation elongation factor 1-α (TEF1) genes supports the inclusion of O. haidensisas a distinct member within the O. piceaecomplex. To our knowledge, this is the first report of a blue stain fungus infecting yellow-cedar, an ecologically, culturally, and economically important conifer naturally distributed along the coastal forests of the Pacific Northwest in North America.

The publication of Benjamin Franklin’s collected works has a long and complex history. William Temple Franklin, his grandson, was bequeathed his papers in 1790, but it took until 1815 until he began work on editing them, and it wasn’t until 1818 that the first volume in the series was published. Temple has been much maligned for these delays and for the supposed poor quality of his work. This article rectifies that by looking in detail at the circumstances Temple faced, including the details of his contract with publisher Henry Colburn, the various stages of preparation for the volumes, and the search for a translator for the French edition. Despite the errors and omissions in Temple’s London and Paris editions, his volumes were the most complete to be published until considerably later in the century and are still drawn on by modern editors.

Aim: An evidence gap exists on sex and gender differences in drowning with previous research neglecting females. Drowning studies have largely focused on accidental drowning and submersion, excluding other classifications such as intentional, water transport-related, and undetermined drowning. This study examined all external causes of drowning deaths over a 13-year period in Australia disaggregated by sex. Drowning deaths were compared by sex with drowning classification, year, month, age, place of death, Indigenous status, socioeconomic, and visitor status. Subject and methods: This retrospective total population study included all females and males who died from drowning in Australia from 2006 to 2019. Data was extracted from the Australian Bureau of Statistics Cause of Death Unit Record Files. Australian population data were extracted to calculate the crude death rate and relative risk for drowning. Results: There were 4007 drowning deaths recorded, and females represented 25.2% of drowning fatalities. Females were less likely than males to drown, including by drowning classification, year, month, state, remoteness and visitor status, age, socioeconomic, and Indigenous status. The highest proportion of female drowning deaths were from intentional drowning, fall into swimming pools, and in natural water. Drowning deaths among females increased as age increased. Conclusion: There is a clear need for improved disaggregation of sex and gender in drowning research. Without the detailed exploration of females in drowning statistics there will be limited knowledge translation specific to females. The development of drowning prevention strategies targeted to females is required to reduce the incidence and risk of drowning.

Objective. Physical inactivity is the fourth-leading cause of global mortality and is prevalent among people with lower extremity osteoarthritis. Lower extremity osteoarthritis is the most common arthritis type afflicting older adults, and total joint arthroplasty (TJA) performed to address the condition is Medicare&apos;s largest annual expense. Despite TJA intervention to address the disabling effects of osteoarthritis, physical activity (PA) level remains stable 6 months after TJA; however, the effect of TJA on long-term PA ([greater than or equal to]2 y) in a representative sample of older adults is unknown. The purpose of this study was to test the hypothesis that PA would remain stable in the long term. Methods. In this longitudinal observational study, a probability-weighted difference-in-differences analysis was conducted to observe the predictive margins of nontraumatic hip or knee TJA on levels of vigorous and moderate PA after 2 years. A combined Health and Retirement Study data set of community-dwelling adults who were >55 years old, had symptomatic osteoarthritis, and were in need of TJA between 2008 and 2018 (N = 4652) was used. Results. TJA was not associated with vigorous PA ([delta] = 2.37; SE = 5.23) or moderate PA ([delta] = -2.84; SE = 7.76) after 2 years. Conclusion. TJA was not associated with increased long-term PA in older adults with osteoarthritis. Impact. Physical therapists should not assume that there will be a natural increase in PA after functional recovery from TJA procedures. Older adults with lower extremity osteoarthritis may benefit from PA screening and promotion practices in physical therapy services. Lay Summary. Receiving a total joint replacement does not lead to increased physical activity levels 2 years after surgery. Keywords: Physical Activity, Preventive Health Services, Total Joint Arthroplasty, Introduction Lower extremity (hip or knee) osteoarthritis is the most prevalent joint disorder, a leading cause of chronic pain and disability in older adults, and a significant barrier to physical [...]

AUGUST WILSON: A Life Patti Hartigan Read by Dion Graham, Patti Hartigan [Afterword] This biography of playwright and poet August Wilson contains both narrative and brief passages from some of [...]

OATH AND HONOR: A Memoir and a Warning Liz Cheney Read by Liz Cheney This memoir about the investigation into the Jan. 6, 2021, assault on the Capitol combines an [...]

Richard C. Hottelet was born in Brooklyn, New York, in 1917, to German-immigrant parents who spoke no English at home. After he graduated from Brooklyn College in 1937, Hottelet, who [...]

Further research is needed to help improve both the standard of care and the outcome for patients with treatment-resistant depression. A particularly critical evidence gap exists with respect to whether pharmacological or non-pharmacological augmentation is superior to antidepressant switch, or vice-versa. The objective of this study was to compare the effectiveness of augmentation with aripiprazole or repetitive transcranial magnetic stimulation versus switching to the antidepressant venlafaxine XR (or duloxetine for those not eligible to receive venlafaxine) for treatment-resistant depression. In this multi-site, 8-week, randomized, open-label study, 278 subjects (196 females and 82 males, mean age 45.6 years (SD 15.3)) with treatment-resistant depression were assigned in a 1:1:1 fashion to treatment with either of these three interventions; 235 subjects completed the study. 260 randomized subjects with at least one post-baseline Montgomery-Asberg Depression Rating (MADRS) assessment were included in the analysis. Repetitive transcranial magnetic stimulation (score change (standard error (se)) = −17.39 (1.3) (p= 0.015) but not aripiprazole augmentation (score change (se) = −14.9 (1.1) (p= 0.069) was superior to switch (score change (se) = −13.22 (1.1)) on the MADRS. Aripiprazole (mean change (se) = −37.79 (2.9) (p= 0.003) but not repetitive transcranial magnetic stimulation augmentation (mean change (se) = −42.96 (3.6) (p= 0.031) was superior to switch (mean change (se) = −34.45 (3.0)) on the symptoms of depression questionnaire. Repetitive transcranial magnetic stimulation augmentation was shown to be more effective than switching antidepressants in treatment-resistant depression on the study primary measure. In light of these findings, clinicians should consider repetitive transcranial magnetic stimulation augmentation early-on for treatment-resistant depression.

This article discusses the history of 221b Software Development, a video game development company based in Sheffield, UK, during the late 1980s and early 1990s. The company was founded by David Vout, Nick Kimberley, and Jason Heggie, and they worked on various projects for publishers such as Gremlin Graphics, Alternative Software, and Hi-Tec. Despite their success in producing licensed games like HeroQuest and Predator 2, financial difficulties and a lack of understanding of the industry's direction led to the closure of 221b. The article also includes interviews with former members of the company, who went on to work in various roles within the gaming industry. [Extracted from the article]