A randomized double-blind pilot study to evaluate the efficacy, safety, and tolerability of intravenous iron versus oral iron for the treatment of restless legs syndrome in patients with iron deficiency anemia.

Restless legs syndrome (RLS) is a neurological disorder that can have a profound effect on sleep and quality of life. Idiopathic RLS is associated with brain iron insufficiency despite normal peripheral iron stores. There is, however, a five- to six-fold increase in prevalence of RLS in patients with iron deficiency anemia (IDA). Several open-label trials have demonstrated symptomatic improvement in RLS following treatment of IDA using oral or intravenous iron supplementation. To date, there have been no randomized double-blind controlled trials of intravenous iron compared with oral iron for the treatment of RLS patients with IDA. In the current study, oral ferrous sulfate and ferumoxytol were compared for efficacy and speed of response for treatment of RLS occurring in patients with IDA. The planned recruitment for this study was 70 patients with RLS and IDA, to be randomly assigned 1:1 to oral or intravenous iron, using double-blind, double-dummy procedures. At Week 6, the primary outcomes of Clinical Global Impression-Improvement score and change from baseline in the International Restless Legs Syndrome Study Group rating scale score were assessed. Due to challenges, performing the clinical trial during the COVID-19 pandemic, final-week data were found missing for 30 patients. As a result, in order to maintain the prespecified statistical analysis, an additional 30 patients were recruited. Both IV and oral iron were associated with a marked improvement in RLS symptoms, with no statistically significant difference between treatment groups. No serious adverse events were observed in either treatment group.

PCSK6 and Survival in Idiopathic Pulmonary Fibrosis.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by limited treatment options and high mortality. A better understanding of the molecular drivers of IPF progression is needed. Objectives: To identify and validate molecular determinants of IPF survival. Methods: A staged genome-wide association study was performed using paired genomic and survival data. Stage I cases were drawn from centers across the United States and Europe and stage II cases from Vanderbilt University. Cox proportional hazards regression was used to identify gene variants associated with differential transplantation-free survival (TFS). Stage I variants with nominal significance (P < 5 × 10-5) were advanced for stage II testing and meta-analyzed to identify those reaching genome-wide significance (P < 5 × 10-8). Downstream analyses were performed for genes and proteins associated with variants reaching genome-wide significance. Measurements and Main Results: After quality controls, 1,481 stage I cases and 397 stage II cases were included in the analysis. After filtering, 9,075,629 variants were tested in stage I, with 158 meeting advancement criteria. Four variants associated with TFS with consistent effect direction were identified in stage II, including one in an intron of PCSK6 (proprotein convertase subtilisin/kexin type 6) reaching genome-wide significance (hazard ratio, 4.11 [95% confidence interval, 2.54-6.67]; P = 9.45 × 10-9). PCSK6 protein was highly expressed in IPF lung parenchyma. PCSK6 lung staining intensity, peripheral blood gene expression, and plasma concentration were associated with reduced TFS. Conclusions: We identified four novel variants associated with IPF survival, including one in PCSK6 that reached genome-wide significance. Downstream analyses suggested that PCSK6 protein plays a potentially important role in IPF progression.

A Polygenic Risk Score for Idiopathic Pulmonary Fibrosis and Interstitial Lung Abnormalities.

Rationale: In addition to rare genetic variants and the MUC5B locus, common genetic variants contribute to idiopathic pulmonary fibrosis (IPF) risk. The predictive power of common variants outside the MUC5B locus for IPF and interstitial lung abnormalities (ILAs) is unknown. Objectives: We tested the predictive value of IPF polygenic risk scores (PRSs) with and without the MUC5B region on IPF, ILA, and ILA progression. Methods: We developed PRSs that included (PRS-M5B) and excluded (PRS-NO-M5B) the MUC5B region (500-kb window around rs35705950-T) using an IPF genome-wide association study. We assessed PRS associations with area under the receiver operating characteristic curve (AUC) metrics for IPF, ILA, and ILA progression. Measurements and Main Results: We included 14,650 participants (1,970 IPF; 1,068 ILA) from six multi-ancestry population-based and case-control cohorts. In cases excluded from genome-wide association study, the PRS-M5B (odds ratio [OR] per SD of the score, 3.1; P = 7.1 × 10-95) and PRS-NO-M5B (OR per SD, 2.8; P = 2.5 × 10-87) were associated with IPF. Participants in the top PRS-NO-M5B quintile had ∼sevenfold odds for IPF compared with those in the first quintile. A clinical model predicted IPF (AUC, 0.61); rs35705950-T and PRS-NO-M5B demonstrated higher AUCs (0.73 and 0.7, respectively), and adding both genetic predictors to a clinical model yielded the highest performance (AUC, 0.81). The PRS-NO-M5B was associated with ILA (OR, 1.25) and ILA progression (OR, 1.16) in European ancestry participants. Conclusions: A common genetic variant risk score complements the MUC5B variant to identify individuals at high risk of interstitial lung abnormalities and pulmonary fibrosis.

Residual Lung Abnormalities after COVID-19 Hospitalization: Interim Analysis of the UKILD Post-COVID-19 Study.

Rationale: Shared symptoms and genetic architecture between coronavirus disease (COVID-19) and lung fibrosis suggest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to progressive lung damage. Objectives: The UK Interstitial Lung Disease Consortium (UKILD) post-COVID-19 study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 on the basis of risk strata. Methods: The PHOSP-COVID-19 (Post-Hospitalization COVID-19) study was used to capture routine and research follow-up within 240 days from discharge. Thoracic computed tomography linked by PHOSP-COVID-19 identifiers was scored for the percentage of residual lung abnormalities (ground-glass opacities and reticulations). Risk factors in linked computed tomography were estimated with Bayesian binomial regression, and risk strata were generated. Numbers within strata were used to estimate posthospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol-driven research follow-up. Measurements and Main Results: The interim cohort comprised 3,700 people. Of 209 subjects with linked computed tomography (median, 119 d; interquartile range, 83-155), 166 people (79.4%) had more than 10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (risk ratio [RR], 1.21; 95% credible interval [CrI], 1.05-1.40), percent predicted DlCO less than 80% (RR, 1.25; 95% CrI, 1.00-1.56), and severe admission requiring ventilation support (RR, 1.27; 95% CrI, 1.07-1.55). In the remaining 3,491 people, moderate to very high risk of residual lung abnormalities was classified at 7.8%, and posthospitalization prevalence was estimated at 8.5% (95% CrI, 7.6-9.5), rising to 11.7% (95% CrI, 10.3-13.1) in the sensitivity analysis. Conclusions: Residual lung abnormalities were estimated in up to 11% of people discharged after COVID-19-related hospitalization. Health services should monitor at-risk individuals to elucidate long-term functional implications.

Clinical characteristics and surgical outcomes of transcutaneous versus transconjunctival excision of Wolfring gland ductal cysts.

PURPOSE: To analyze the clinicopathological characteristics and surgical outcomes of patients with Wolfring gland ductal cysts (WGDCs). METHODS: A retrospective, consecutive, interventional comparative case series was performed over a period of 7 years. Data on demographic and clinical characteristics, pathological findings and outcomes of surgically excised cysts were collected. A comparison between the transconjunctival and transcutaneous approaches was also assessed. RESULTS: Forty-eight patients (48 eyelids) were included in the final analysis. The most common presenting symptom was painless eyelid swelling (81.3%). The median symptom duration was 11.5 months (IQR, 18.25). The upper eyelid was involved in 31 (64.6%) patients, 29/31 of whom had cysts in a medial or centromedial location. Forty-five (93.8%) cysts were bluish gray and transilluminable with clear contents on lid eversion and a median largest dimension of 22 mm (IQR, 8). A transverse conjunctival fibrotic band was observed along the proximal tarsal border in the cyst area in all patients. Signs of chronic trachoma were noted in 38 (79.2%) patients. Preoperative significant ptosis was present in 28/31 (90.3%) of the upper eyelid cysts. Thirty cysts (62.5%) were excised through the skin, and 18 cysts (37.5%) were excised transconjunctivally. Intraoperative cyst rupture, the need for conjunctival grafting and postoperative residual upper lid ptosis were significantly greater in the transconjunctival group (p = 0.009, p < 0.001, and p = 0.016, respectively). CONCLUSION: The present study highlights the clinicopathological characteristics of a relatively large series of surgically excised WGDCs. Transcutaneous excision of WGDCs has proven to be an effective treatment with fewer adverse sequelae than the transconjunctival approach.

Exploring techniques for encoding spoken instructions in working memory: a comparison of verbal rehearsal, motor imagery, self-enactment and action observation.

Encoding and recalling spoken instructions is subject to working memory capacity limits. Previous research suggests action-based encoding facilitates instruction recall, but has not directly compared benefits across different types of action-based techniques. The current study addressed this in two experiments with young adults. In Experiment 1, participants listened to instructional sequences containing four action-object pairs, and encoded these instructions using either a motor imagery or verbal rehearsal technique, followed by recall via oral repetition or enactment. Memory for instructions was better when participants used a motor imagery technique during encoding, and when recalling the instructions by enactment. The advantage of using a motor imagery technique was present in both verbal and enacted recall. In Experiment 2, participants encoded spoken instructions whilst implementing one of four techniques (verbal rehearsal, motor imagery, observation of others' actions or self-enactment), and then recalled the instructions by oral repetition or enactment. For both verbal and enacted recall, memory for instructions was least accurate in the rehearsal condition, while the other encoding conditions did not differ from each other. These novel findings indicate similar benefits of imagining, observation and execution of actions in encoding spoken instructions, and enrich current understanding of action-based benefits in working memory.

A swinging upper eyelid approach for excision of lacrimal gland masses.

PURPOSE: To describe a novel transconjunctival technique for excision of well-defined masses of the orbital lobe of the lacrimal gland. METHODS: Case series of three patients undergoing excision of a well-defined mass of the orbital lobe of lacrimal gland using a swinging upper eyelid flap. This technique entails a supratarsal conjunctival incision combined with lateral canthotomy and superior cantholysis. RESULTS: Complete removal of the mass without visible scars was achieved in all cases. There were no complications related to this approach. CONCLUSION: The swinging upper eyelid approach produces a wide exposure of the superolateral orbit. It allows safe removal of large lacrimal gland masses without the need for bone removal, while affording acceptable cosmesis.

Age and number of lesions predict chalazion recurrence.

PURPOSE: Periocular lesions in pediatric patients usually require general anesthesia for surgical intervention. The US Food and Drug Administration (FDA) warns against multiple exposures to anesthesia in children younger than 3 years due to the increased risk of learning disabilities in this population. This study aimed to evaluate risk factors associated with chalazion recurrence after surgery. METHODS: A retrospective chart review over a five-year period identified 649 patients at our institution undergoing surgical intervention for chalazion. The primary outcomes examined were as follows: (1) return to the operating room for additional surgical intervention and (2) recurrence of chalazion during convalescence from surgery and follow-up. RESULTS: Fewer than one-third of patients suffered a recurrence after surgery. Multivariate logistic regression found younger age (p = 0.01), female sex (p = 0.01), and a greater number of chalazia drained (p < 0.001) were significantly correlated with recurrence of chalazia after surgery. CONCLUSIONS: Patients presenting at a younger age and with a greater number of chalazion were statistically more likely to have a recurrence of chalazion after surgery. Given recurrence is more likely in younger children, reconciling this with the risk-benefit ratio with regard to FDA guidelines on anesthesia in children under three years is a critical consideration for ophthalmologists.

Reassessing the association of MUC5B with survival in idiopathic pulmonary fibrosis.

A variant in the mucin 5B gene (MUC5B) is strongly associated with the risk of idiopathic pulmonary fibrosis. However, the same variant is associated with increased survival time. Previous work suggested that this may be explained by index event bias, with the true effect being to decrease survival. Here, we reassessed this claim using more recent methods and datasets. We found that the statistical assumptions of the previous analysis did not hold, and instead, we applied recent methods of corrected weighted least squares, MR-RAPS and Slope-hunter to both the previous data and an updated consortium meta-analysis. However, these analyses did not yield robust evidence for increased or decreased survival. In simulations of a true effect of decreased survival, we did not observe any realistic scenario in which index event bias led to an observed effect of increased survival. We therefore regard as unsafe the claim that MUC5B has a true effect of decreased survival. Alternative explanations should be sought to explain the observed association with increased survival.

The causal relationship between gastro-oesophageal reflux disease and idiopathic pulmonary fibrosis: a bidirectional two-sample Mendelian randomisation study.

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is associated with idiopathic pulmonary fibrosis (IPF) in observational studies. It is not known if this association arises because GORD causes IPF or because IPF causes GORD, or because of confounding by factors, such as smoking, associated with both GORD and IPF. We used bidirectional Mendelian randomisation (MR), where genetic variants are used as instrumental variables to address issues of confounding and reverse causation, to examine how, if at all, GORD and IPF are causally related. METHODS: A bidirectional two-sample MR was performed to estimate the causal effect of GORD on IPF risk and of IPF on GORD risk, using genetic data from the largest GORD (78 707 cases and 288 734 controls) and IPF (4125 cases and 20 464 controls) genome-wide association meta-analyses currently available. RESULTS: GORD increased the risk of IPF, with an OR of 1.6 (95% CI 1.04-2.49; p=0.032). There was no evidence of a causal effect of IPF on the risk of GORD, with an OR of 0.999 (95% CI 0.997-1.000; p=0.245). CONCLUSIONS: We found that GORD increases the risk of IPF, but found no evidence that IPF increases the risk of GORD. GORD should be considered in future studies of IPF risk and interest in it as a potential therapeutic target should be renewed. The mechanisms underlying the effect of GORD on IPF should also be investigated.

Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection.

BACKGROUND: Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment. METHODS: We conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (p<5×10-8) were investigated in additional independent studies, were fine-mapped and putative causal genes identified by gene expression analysis. GWASs of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease among the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWASs). RESULTS: From a GWAS of 9714 cases and 48 471 controls, we identified six novel genome-wide significant signals for chronic sputum production including signals in the human leukocyte antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and FUT2 locus. The four common variant associations were supported by independent studies with a combined sample size of up to 2203 cases and 17 627 controls. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations including blood cell traits, liver biomarkers, infections, gastrointestinal and thyroid-associated diseases, and respiratory disease. CONCLUSIONS: Novel signals at the FUT2 and mucin loci suggest that mucin fucosylation may be a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention.

Negative interactions and virulence differences drive the dynamics in multispecies bacterial infections.

Bacterial infections are often polymicrobial, leading to intricate pathogen-pathogen and pathogen-host interactions. There is increasing interest in studying the molecular basis of pathogen interactions and how such mechanisms impact host morbidity. However, much less is known about the ecological dynamics between pathogens and how they affect virulence and host survival. Here we address these open issues by co-infecting larvae of the insect model host Galleria mellonella with one, two, three or four bacterial species, all of which are opportunistic human pathogens. We found that host mortality was always determined by the most virulent species regardless of the number of species and pathogen combinations injected. In certain combinations, the more virulent pathogen simply outgrew the less virulent pathogen. In other combinations, we found evidence for negative interactions between pathogens inside the host, whereby the more virulent pathogen typically won a competition. Taken together, our findings reveal positive associations between a pathogen's growth inside the host, its competitiveness towards other pathogens and its virulence. Beyond being generalizable across species combinations, our findings predict that treatments against polymicrobial infections should first target the most virulent species to reduce host morbidity, a prediction we validated experimentally.

Does repetitive transcranial magnetic stimulation improve cognitive function in age-related neurodegenerative diseases? A systematic review and meta-analysis.

OBJECTIVE: High-frequency, repetitive transcranial magnetic stimulation (rTMS) targeted over the dorsolateral prefrontal cortex (DLPFC) is widely used in research to promote neuroplasticity and cognitive enhancement. RTMS is a promising intervention to tackle cognitive decline in people with age-related neurodegenerative diseases. However, there is currently no systematic evidence examining the effects of DLPFC-targeted, high-frequency rTMS on cognitive function in this population. The aim of this systematic review was to evaluate the efficacy and moderators of this treatment intervention. METHODS: A comprehensive literature search of five electronic databases was performed to identify articles published before October, 2022. Following PRISMA guidelines, the identified articles were screened, data was extracted, and the methodological quality was assessed using the Cochrane tool, Risk of Bias 2. Meta-analyses were performed using R Studio (v.4.1.2). RESULTS: Sixteen studies involving 474 participants met the inclusion criteria, of which 8 studies measured global cognitive function. The results from the random-effects meta-analysis showed rTMS significantly improved global cognitive function relative to control groups shown by a large, significant effect size (g = 1.39, 95% CI, 0.34-2.43; p = 0.017). No significant effects were found between subgroups or for individual cognitive domains. CONCLUSIONS: High-frequency rTMS, targeted over the DLPFC, appears to improve global cognitive function in people with age-related neurodegenerative diseases. However, these results should be interpreted with caution due to the small number of studies included, and high between-study heterogeneity.

Hanging on the telephone: Maintaining visuospatial bootstrapping over time in working memory.

Visuospatial bootstrapping (VSB) refers to the phenomenon in which performance on a verbal working memory task can be enhanced by presenting the verbal material within a familiar visuospatial configuration. This effect is part of a broader literature concerning how working memory is influenced by use of multimodal codes and contributions from long-term memory. The present study aimed to establish whether the VSB effect extends over a brief (5-s) delay period, and to explore the possible mechanisms operating during retention. The VSB effect, as indicated by a verbal recall advantage for digit sequences presented within a familiar visuospatial configuration (modelled on the T-9 keypad) relative to a single-location display, was observed across four experiments. The presence and size of this effect changed with the type of concurrent task activity applied during the delay. Articulatory suppression (Experiment 1) increased the visuospatial display advantage, while spatial tapping (Experiment 2) and a visuospatial judgment task (Experiment 3) both removed it. Finally, manipulation of the attentional demands placed by a verbal task also reduced (but did not abolish) this effect (Experiment 4). This pattern of findings demonstrates how provision of familiar visuospatial information at encoding can continue to support verbal working memory over time, with varying demands on modality-specific and general processing resources.

Intentional and incidental odour-colour binding in working memory.

The question of how features are bound together in working memory has become a topic of much research in recent years. However, this is typically focused on visual and/or auditory stimuli. The purpose of this study is to apply established feature binding procedures to investigate odour binding in working memory. Across three experiments, memory for intentionally and incidentally formed odour-colour pairings was tested. Experiment 1 showed that following explicit instruction to remember the odour-colour combinations, young adults can recall lists of 3-pairings at levels above that of chance and exhibit a recency advantage for the last pairing. In Experiment 2 participants were asked to prioritise the first pairing in the list or treat all pairings equally. We observed only limited evidence of prioritisation affecting the serial position function. Experiment 3 explored incidental odour-colour binding. Using a yes/no recognition procedure, accuracy did not differ for positive test probes presented in the same (bound) or different (unbound) colour to encoding. This study is one of the first to examine odour-colour binding in working memory and, taking the evidence together, suggests that odour-colour bindings can be formed in working memory; however, functionality may be limited compared to that of visual feature binding.

The Overweight and Obese Patient in Oculofacial Plastic Surgery: A Narrative Review.

PURPOSE: The oculofacial plastic surgeon will more frequently encounter challenges related to overweight and obese patients as the incidence rises. There is a paucity of data in the oculofacial plastic surgical literature regarding this topic. The goal of this review is to detail the role obesity plays in the perioperative course and the considerations for a surgeon treating this patient population. METHODS: The authors conducted a computerized search using PubMed, Embase, and Google Scholar. The search terms used were "(obesity OR overweight) AND surgery," "(obesity OR overweight) AND oculoplastic," "(obesity OR overweight) AND oculofacial," "(obesity OR overweight) AND 'facial plastic surgery', " "(obesity OR overweight) AND 'bariatric surgery', " "(obesity OR overweight) AND (pre-operative OR post-operative OR intraoperative," " (obesity OR overweight) AND complications," "(obesity OR overweight) AND (facial plastic surgery) AND complications)," "(obesity OR overweight) AND eyelid," "(obesity OR overweight) AND (nasolacrimal OR 'nasolacrimal duct')," "(obesity OR overweight) AND IIH," "(obesity OR overweight) AND exophthalmos." RESULTS: A total of 127 articles, published from 1952 to 2022 in the English language or with English translations were included. Articles published earlier than 2000 were cited for foundational knowledge. References cited in the identified articles were also used to gather further data for the review. CONCLUSIONS: Overweight and obese patients pose specific challenges that the oculofacial plastic surgeon should be aware of to better optimize patient outcomes. Multiple comorbidities, poor wound healing, and nutritional deficits all contribute to the complications experienced in this patient population. Further investigation on overweight and obese patients is needed.

Toward Structural Health Monitoring with the MyShake Smartphone Network.

The field of structural health monitoring (SHM) faces a fundamental challenge related to accessibility. While analytical and empirical models and laboratory tests can provide engineers with an estimate of a structure's expected behavior under various loads, measurements of actual buildings require the installation and maintenance of sensors to collect observations. This is costly in terms of power and resources. MyShake, the free seismology smartphone app, aims to advance SHM by leveraging the presence of accelerometers in all smartphones and the wide usage of smartphones globally. MyShake records acceleration waveforms during earthquakes. Because phones are most typically located in buildings, a waveform recorded by MyShake contains response information from the structure in which the phone is located. This represents a free, potentially ubiquitous method of conducting critical structural measurements. In this work, we present preliminary findings that demonstrate the efficacy of smartphones for extracting the fundamental frequency of buildings, benchmarked against traditional accelerometers in a shake table test. Additionally, we present seven proof-of-concept examples of data collected by anonymous and privately owned smartphones running the MyShake app in real buildings, and assess the fundamental frequencies we measure. In all cases, the measured fundamental frequency is found to be reasonable and within an expected range in comparison with several commonly used empirical equations. For one irregularly shaped building, three separate measurements made over the course of four months fall within 7% of each other, validating the accuracy of MyShake measurements and illustrating how repeat observations can improve the robustness of the structural health catalog we aim to build.

Targeted therapy and immunotherapy for orbital and periorbital tumors: a major review.

Traditionally, for patients who are poor candidates for surgery and/or radiotherapy, palliative chemotherapy is often offered but with significant toxic side effects. However, recent advancements in our understanding of tumor biology and molecular genetics have brought new understanding to the molecular pathways of certain tumors and cancers. This has ushered in a new era of precision medicine specific to a tumor or cancer treatment pathway (targeted therapy) or directed to host-tumor responses (immunotherapy). This article will focus on recent updates in the application of available targeted and immunotherapy for managing orbital and periorbital tumors and tumor-like conditions, which include cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, cutaneous melanoma, Merkel cell carcinoma, sebaceous gland carcinoma, solitary fibrous tumor, dermatofibrosarcoma protuberans, orbital meningioma, neurofibromatosis, Langerhans cell histiocytosis, ocular adnexal lymphoma, orbital lymphatic malformation, and adenoid cystic carcinoma.

Intact high-resolution working memory binding in a patient with developmental amnesia and selective hippocampal damage.

Debate continues regarding the possible role of the hippocampus across short-term and working memory tasks. The current study examined the possibility of a hippocampal contribution to precise, high-resolution cognition and conjunctive memory. We administered visual working memory tasks featuring a continuous response component to a well-established developmental amnesic patient with relatively selective bilateral hippocampal damage (Jon) and healthy controls. The patient was able to produce highly accurate response judgments regarding conjunctions of color and orientation or color and location, using simultaneous or sequential presentation of stimuli, with no evidence of any impairment in working memory binding, categorical accuracy, or continuous precision. These findings indicate that hippocampal damage does not necessarily lead to deficits in high-resolution cognitive performance, even when the damage is severe and bilateral.

Ethical review of COVID-19 vaccination requirements for transplant center staff and patients.

Transplant centers seeking to increase coronavirus disease 2019 (COVID-19) vaccine coverage may consider requiring vaccination for healthcare workers or for candidates. The authors summarize current data to inform an ethical analysis of the harms, benefits, and individual and societal impact of mandatory vaccination, concluding that vaccine requirements for healthcare workers and transplant candidates are ethically justified by beneficence, net utility, and fiduciary duty to patients and public health. Implementation strategies should mitigate concerns about respect for autonomy and transparency for both groups. We clarify how the same arguments might be applied to related questions of caregiver vaccination, allocation of other healthcare resources, and mandates for non-COVID-19 vaccines. Finally, we call for effort to achieve global equity in vaccination as soon as possible.