Roles and interplay of reinforcement-based and error-based processes during reaching and gait in neurotypical adults and individuals with Parkinson's disease.

From a game of darts to neurorehabilitation, the ability to explore and fine tune our movements is critical for success. Past work has shown that exploratory motor behaviour in response to reinforcement (reward) feedback is closely linked with the basal ganglia, while movement corrections in response to error feedback is commonly attributed to the cerebellum. While our past work has shown these processes are dissociable during adaptation, it is unknown how they uniquely impact exploratory behaviour. Moreover, converging neuroanatomical evidence shows direct and indirect connections between the basal ganglia and cerebellum, suggesting that there is an interaction between reinforcement-based and error-based neural processes. Here we examine the unique roles and interaction between reinforcement-based and error-based processes on sensorimotor exploration in a neurotypical population. We also recruited individuals with Parkinson's disease to gain mechanistic insight into the role of the basal ganglia and associated reinforcement pathways in sensorimotor exploration. Across three reaching experiments, participants were given either reinforcement feedback, error feedback, or simultaneously both reinforcement & error feedback during a sensorimotor task that encouraged exploration. Our reaching results, a re-analysis of a previous gait experiment, and our model suggests that in isolation, reinforcement-based and error-based processes respectively boost and suppress exploration. When acting in concert, we found that reinforcement-based and error-based processes interact by mutually opposing one another. Finally, we found that those with Parkinson's disease had decreased exploration when receiving reinforcement feedback, supporting the notion that compromised reinforcement-based processes reduces the ability to explore new motor actions. Understanding the unique and interacting roles of reinforcement-based and error-based processes may help to inform neurorehabilitation paradigms where it is important to discover new and successful motor actions.

Lumbar Fusion Surgical Prophylaxis Using Cefazolin vs. Vancomycin in the Penicillin-Allergic Patient.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To compare peri- and postoperative infection rates among patients with mild to moderate penicillin allergies who receive cefazolin vs vancomycin as prophylaxis for lumbar fusion. Additionally, we sought to determine if patients receiving cefazolin exhibited any clinical symptoms suggestive of drug-induced hypersensitivity reactions, and to compare those rates to patients who received vancomycin. SUMMARY OF BACKGROUND DATA: Cefazolin has been historically linked to hypersensitivity reactions in penicillin-allergic patients due to cross-reactivity. As a result, vancomycin is often given to these patients instead. To our knowledge, no studies have directly compared these two antibiotics in penicillin-allergic patients undergoing lumbar fusion. METHODS: Patients with mild to moderate documented penicillin allergies who underwent lumbar fusion from 2017-2022 and received prophylactic cefazolin or vancomycin were studied. Demographic, surgical information, and hospital length of stay (LOS) were recorded. We identified drug sensitivity reactions, in hospital infections, 90-day readmissions related to infectious etiologies and need for irrigation and debridement (I&D) to treat a surgical site infection. RESULTS: 222 patients received cefazolin, while 180 received vancomycin. Patients receiving vancomycin had more medical comorbidities, while patients receiving cefazolin had slightly more levels fused. No significant differences existed between cohorts in postoperative infection rate. One patient given cefazolin developed a mild drug-induced skin reaction that was treated with topical steroids. No significant differences existed between cohorts in 90-day readmissions or need for I&D surgery. On bivariate analysis, patients given cefazolin had a longer LOS but this was attributed to confounding variables on multivariate analysis. CONCLUSIONS: Cefazolin and vancomycin are comparable at preventing postoperative infections among patients with mild to moderate documented reactions to penicillin. Our findings also suggest that penicillin-allergic patients are not at higher risk of developing drug-related hypersensitivity reactions in response to cefazolin exposure when compared to those who received vancomycin.

Reporting bias, not external focus: A robust Bayesian meta-analysis and systematic review of the external focus of attention literature.

Evidence has ostensibly been accumulating over the past 2 decades suggesting that an external focus on the intended movement effect (e.g., on the golf club during a swing) is superior to an internal focus on body movements (e.g., on your arms during a swing) for skill acquisition. Seven previous meta-studies have all reported evidence of external focus superiority. The most comprehensive of these concluded that an external focus enhances motor skill retention, transfer, and performance and leads to reduced eletromyographic activity during performance and that more distal external foci are superior to proximal external foci for performance. Here, we reanalyzed these data using robust Bayesian meta-analyses that included several plausible models of publication bias. We found moderate to strong evidence of publication bias for all analyses. After correcting for publication bias, estimated mean effects were negligible: g = 0.01 (performance), g = 0.15 (retention), g = 0.09 (transfer), g = 0.06 (electromyography), and g = -0.01 (distance effect). Bayes factors indicated data favored the null for each analysis, ranging from BF01 = 1.3 (retention) to 5.75 (performance). We found clear evidence of heterogeneity in each analysis, suggesting the impact of attentional focus depends on yet unknown contextual factors. Our results contradict the existing consensus that an external focus is always more effective than an internal focus. Instead, focus of attention appears to have a variety of effects that we cannot account for, and, on average, those effects are small to nil. These results parallel previous metascience suggesting publication bias has obfuscated the motor learning literature. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A conceptual model for assessing the risk of unidentified pain.

Untreated or undertreated pain is well established as a significant problem, but unidentified pain is a distinct construct that still needs to be clearly modeled or fully described. This paper aims to develop a conceptual model of unidentified pain in humans with the goal of future development of an unidentified pain risk tool. A multi-phase process was employed consisting sequentially of 1) brainstorming followed by consensus building, 2) peer-review and publication of an integrative theoretical review protocol for "unidentified pain," 3) conduct of the integrative review, and 4) a repeated brainstorming session to identify areas of risk for unidentified pain to produce a conceptual model. Brainstorming led to a consensus on "unidentified pain" as the concept of interest, followed by developing a review protocol. Twenty-four abstracts were reviewed after database searches, and four articles were included for full-text review. Three pain risk areas (hazards) were identified: cognition/communication problems, being alone or in the absence of a surrogate/proxy report, and the presence of known painful conditions or treatments and a conceptual model was developed. The hazards are posited to have the potential to both interact and be cumulative, increasing the risk for unidentified pain. There is currently no risk tool for assessing unidentified pain. The development of this conceptual model will be used for future development and psychometric testing of a tool to recognize the risk for unidentified pain in humans. PERSPECTIVE: This focus article describes the development a conceptual model for the concept of unidentified pain in humans. This pain may occur in individuals who experience one or more interactive and cumulative hazards: cognition/communication problems, being alone, absence of a surrogate/proxy report, or presence of known painful conditions or treatments.

Shared neutrophil and T cell dysfunction is accompanied by a distinct interferon signature during severe febrile illnesses in children.

Severe febrile illnesses in children encompass life-threatening organ dysfunction caused by diverse pathogens and other severe inflammatory syndromes. A comparative approach to these illnesses may identify shared and distinct features of host immune dysfunction amenable to immunomodulation. Here, using immunophenotyping with mass cytometry and cell stimulation experiments, we illustrate trajectories of immune dysfunction in 74 children with multi-system inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2, 30 with bacterial infection, 16 with viral infection, 8 with Kawasaki disease, and 42 controls. We explore these findings in a secondary cohort of 500 children with these illnesses and 134 controls. We show that neutrophil activation and apoptosis are prominent in multi-system inflammatory syndrome, and that this is partially shared with bacterial infection. We show that memory T cells from patients with multi-system inflammatory syndrome and bacterial infection are exhausted. In contrast, we show viral infection to be characterized by a distinct signature of decreased interferon signaling and lower interferon receptor gene expression. Improved understanding of immune dysfunction may improve approaches to immunomodulator therapy in severe febrile illnesses in children.

Medial Patellofemoral Ligament Reconstruction Improves Patella Alta.

BACKGROUND: Patellofemoral instability (PFI) is a common problem with various anatomic risk factors identified, including patella alta as one of the most powerful predictors. Given that the medial patellofemoral ligament (MPFL) is the primary soft tissue stabilizer of the patella, a common procedure to treat recurrent patellar instability is MPFL reconstruction. The aim of this study is to examine the relationship between MPFL reconstruction and patellar height. We hypothesize that after reconstruction, patellar instability patients would have demonstrable reduction in patella height and patella alta correction. METHODS: Patient records were queried for patients who underwent MPFL reconstruction for recurrent patellar instability. Patient and operative demographics were collected. We measured Insall-Salvati ratio (ISR), Caton Deschamps index (CDI), and Blackburne-Peel ratio (BPR) in all patients at various time points. The height indices were compared across the preoperative, immediately postoperative, and 6-month time points in a pairwise fashion using paired-sample t-tests. Further subgroup analysis of patients (n=27) with elevated preoperative Caton Deschamps Index (defined as >1.3) was completed. RESULTS: The final cohort was 103 patients. There was a significant difference between pre- and postoperative ISR (P<0.001) and at 6-month follow up (P<0.001), between preoperative CDI and the 6-month follow-up (P<0.0010), and between the postoperative and preoperative CDI (P<0.001). There was also a difference between preoperative and postoperative BPR (P<0.001), as well as between the preoperative and 6-month follow-up BPR (P=0.002). Twenty-seven patients had an initial CDI greater than 1.3. Differences were observed between pre- and postoperative mean CDI (P=0.001) and at 6-month follow-up (P=0.006), between both postoperative and 6-month ISR (both P<0.001), and preoperative mean BPR and the postoperative (P=0.004) and 6-month mean BPR (P=0.027). CONCLUSIONS: Patients with pre-existing patella alta and recurrent patella dislocations who undergo isolated MPFL reconstruction have decreased patella alta at their 6-month follow-up as measured by ISR, CDI, and BPR. Patients without patella alta do not demonstrate statistically significant differences after their MPFL reconstruction. LEVEL OF EVIDENCE: III (retrospective comparative study).

Surgeon- and hospital-level variation in wait times for scheduled non-urgent surgery in Ontario, Canada: A cross-sectional population-based study.

BACKGROUND: Canadian health systems fare poorly in providing timely access to elective surgical care, which is crucial for quality, trust, and satisfaction. METHODS: We conducted a cross-sectional analysis of surgical wait times for adults receiving non-urgent cataract surgery, knee arthroplasty, hip arthroplasty, gallbladder surgery, and non-cancer uterine surgery in Ontario, Canada, between 2013 and 2019. We obtained data from the Wait Times Information System (WTIS) database. Inter- and intra-hospital and surgeon variations in wait time were described graphically with caterpillar plots. We used non-nested 3-level hierarchical random effects models to estimate variation partition coefficients, quantifying the proportion of wait time variance attributable to surgeons and hospitals. RESULTS: A total of 942,605 procedures at 107 healthcare facilities, conducted by 1,834 surgeons, were included in the analysis. We observed significant intra- and inter-provider variations in wait times across all five surgical procedures. Inter-facility median wait time varied between six-fold for gallbladder surgery and 15-fold for knee arthroplasty. Inter-surgeon variation was more pronounced, ranging from a 17-fold median wait time difference for cataract surgery to a 216-fold difference for non-cancer uterine surgery. The proportion of variation in wait times attributable to facilities ranged from 6.2% for gallbladder surgery to 23.0% for cataract surgery. In comparison, surgeon-related variation ranged from 16.0% for non-cancer uterine surgery to 28.0% for cataract surgery. IMPLICATIONS: There is extreme variability in surgical wait times for five common, high-volume, non-urgent surgical procedures. Strategies to address surgical wait times must address the variation between service providers through better coordination of supply and demand. Approaches such as single-entry models could improve surgical system performance.

The burden and contemporary epidemiology of sepsis in children.

Sepsis is a dysregulated host response to infection that leads to life-threatening organ dysfunction. Half of the 50 million people affected by sepsis globally every year are neonates and children younger than 19 years. This burden on the paediatric population translates into a disproportionate impact on global child health in terms of years of life lost, morbidity, and lost opportunities for children to reach their developmental potential. This Series on paediatric sepsis presents the current state of diagnosis and treatment of sepsis in children, and maps the challenges in alleviating the burden on children, their families, and society. Drawing on diverse experience and multidisciplinary expertise, we offer a roadmap to improving outcomes for children with sepsis. This first paper of the Series is a narrative review of the burden of paediatric sepsis from low-income to high-income settings. Advances towards improved operationalisation of paediatric sepsis across all age groups have facilitated more standardised assessment of the Global Burden of Disease estimates of the impact of sepsis on child health, and these estimates are expected to gain further precision with the roll out of the new Phoenix criteria for sepsis. Sepsis remains one of the leading causes of childhood morbidity and mortality, with immense direct and indirect societal costs. Although substantial regional differences persist in relation to incidence, microbiological epidemiology, and outcomes, these cannot be explained by differences in income level alone. Recent insights into post-discharge sequelae after paediatric sepsis, ranging from late mortality and persistent neurodevelopmental impairment to reduced health-related quality of life, show how common post-sepsis syndrome is in children. Targeting sepsis as a key contributor to poor health outcomes in children is therefore an essential component of efforts to meet the Sustainable Development Goals.

Susceptibility to childhood sepsis, contemporary management, and future directions.

Sepsis disproportionally affects children across all health-care settings and is one of the leading causes of morbidity and mortality in neonatal and paediatric age groups. As shown in the first paper in this Series, the age-specific incidence of sepsis is highest during the first years of life, before approaching adult incidence rates during adolescence. In the second paper in this Series, we focus on the unique susceptibility of paediatric patients to sepsis and how the underlying dysregulated host response relates to developmental aspects of children's immune system, genetic, perinatal, and environmental factors, and comorbidities and socioeconomic determinants of health, which often differ between children and adults. State-of-the-art clinical management of paediatric sepsis is organised around three treatment pillars-diagnosis, early resuscitation, and titration of advanced care-and we examine available treatment guidelines and the limitations of their supporting evidence. Serious evidence gaps remain in key areas of paediatric sepsis care, especially surrounding recognition, common interventions, and survivor support, and to this end we offer a research roadmap for the next decade that could accelerate targeted diagnostics and personalised use of immunomodulation. However, improving outcomes for children with sepsis relies fundamentally on systematic quality improvement in both recognition and treatment, which is the theme of the third paper in this Series. Digital health, as shown in the fourth and final paper of this Series, holds promising potential in breaking down the barriers that hinder progress in paediatric sepsis care and, ultimately, global child health.

Postoperative opioid consumption patterns diverge between propensity matched patients undergoing traumatic and elective cervical spine fusion.

BACKGROUND CONTEXT: Prolonged opioid therapy following spine surgery is an ongoing postoperative concern. While prior studies have investigated postoperative opioid use patterns in the elective cervical surgery patient population, to our knowledge, opioid use patterns in patients undergoing surgery for traumatic cervical spine injuries have not been elucidated. PURPOSE: The purpose of this study was to compare opioid use and prescription patterns in the postoperative pain management of patients undergoing traumatic and elective cervical spine fusion surgery. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Adult patients with traumatic cervical injuries who underwent primary anterior cervical discectomy and fusion (ACDF) or posterior cervical decompression and fusion (PCDF) during their initial hospital admission. The propensity matched, control group consisted of adult elective cervical fusion patients who underwent primary ACDF or PCDF. OUTCOME MEASURES: Demographic data, surgical characteristics, spinal disease diagnosis, location of cervical injury, procedure type, operative levels fused, and Prescription Drug Monitoring Program (PDMP) data. PDMP data included the number of opioid prescriptions filled, preoperative opioid use, postoperative opioid use, and use of perioperative benzodiazepines, muscle relaxants, or gabapentin. Opioid consumption data was collected in morphine milligram equivalents (MME) and standardized per day. METHODS: A 1:1 propensity match was performed to match traumatic injury patients undergoing cervical fusion surgery with elective cervical fusion patients. Traumatic injury patients were matched based on age, sex, CCI, procedure type, and cervical levels fused. Pre- and postoperative opioid, benzodiazepine, muscle relaxant, and gabapentin use were assessed for the traumatic injury and elective patients. T- or Mann-Whitney U tests were used to compare continuous data and Chi-Squared or Fisher's Exact were used to compare categorical data. Multivariate stepwise regression using MME per day 0 - 30 days following surgery as the dependent outcome was performed to further evaluate associations with postoperative opioid use. RESULTS: A total of 48 patients underwent fusion surgery for a traumatic cervical spine injury and 48 elective cervical fusion with complete PDMP data were assessed. Elective patients were found to fill more prescriptions (3.19 vs 0.65, p=.023) and take more morphine milligram equivalents (MME) per day (0.60 vs 0.04, p=.014) within 1 year prior to surgery in comparison to traumatic patients. Elective patients were also more likely to use opioids (29.2% vs 10.4%, p=.040) and take more MMEs per day (0.70 vs 0.05, p=.004) within 30 days prior to surgery. Within 30 days postoperatively, elective patients used opioids more frequently (89.6% vs 52.1%, p<.001) and took more MMEs per day (3.73 vs 1.71, p<.001) than traumatic injury patients. Multivariate stepwise regression demonstrated preoperative opioid use (Estimate: 1.87, p=.013) to be correlated with higher postoperative MME per day within 30 days of surgery. Surgery after traumatic injury was correlated with lower postoperative MME use per day within 30 days of surgery (Estimate: -1.63 p=.022). CONCLUSION: Cervical fusion patients with a history of traumatic spine injury consume fewer opioids in the early postoperative period in comparison to elective cervical fusion patients, however both cohorts consumed a similar amount after the initial 30-day postoperative period. Preoperative opioid use was also a risk factor for higher consumption in the short-term postoperative period. These results may aid physicians in further understanding patients' postoperative care needs based on presenting injury characteristics and highlights the need for enhanced follow-up care for traumatic cervical spine injury patients after fusion surgery.

The Role of L1PA in Patient-reported Outcomes in Patients Undergoing Single-level Lumbar Fusion for Degenerative Spondylolisthesis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine whether the L1 pelvic angle (L1PA) can be used to predict quality of life outcomes for adults one year after L4-L5 fusion to treat degenerative spondylolisthesis. SUMMARY OF BACKGROUND DATA: L1PA is beneficial in the evaluation of preoperative and postoperative quality of life outcomes in patients undergoing surgery for spinal deformity. No studies have examined its utility in surgical patients with degenerative spinal disease. METHODS: Patients undergoing L4-L5 posterolateral decompression and fusion or transforaminal lumbar interbody fusion for degenerative lumbar spondylolisthesis were grouped by preoperative and postoperative L1PA, and further stratified by cut offs of >7.2° and <7.2° based on previous literature. We also stratified patients by presence of an ideal calculated L1PA, defined as (0.5×Pelvic incidence) -21 +/-5°, as proposed by prior literature. Preoperative, one-year postoperative and Δ (postoperative minus preoperative) patient-reported outcome measures (PROMs) and radiographic measurements were collected. RESULTS: Twenty-four patients were identified with preoperative L1PAs <7.2° and 132 with L1PAs >7.2°. Eighteen patients were identified with postoperative L1PAs <7.2° and 138 with L1PAs>7.2°. Sixty-five and fifty-seven patients were identified as having ideal calculated preoperative and postoperative L1PAs, respectively. When using absolute cutoffs, L1PA correlated with pelvic tilt, pelvic incidence, and pelvic incidence-lumbar lordosis mismatch (PI-LL). When using calculated L1PAs, L1PA correlated with lumbar lordosis, PI-LL, pelvic tilt and sacral slope. With respect to PROMs, no statistically significant differences existed between cohorts both preoperatively and at one-year postoperatively on either univariate and multivariate analyses. CONCLUSION: L1PA may be a helpful radiographic consideration that translates to clinically relevant outcomes in spinal deformity. However, it does not appear as predictive of patient outcomes after single-level fusion for patients with L4-L5 degenerative spondylolisthesis. Further studies are warranted to investigate the role of L1PA in degenerative spine patients.

Evaluation of Acute and Convalescent Antibody Concentration Against Pneumococcal Capsular Polysaccharides for the Diagnosis of Pneumococcal Infection in Children with Community-Acquired Pneumonia.

We evaluated whether the quantification of IgG to pneumococcal capsular polysaccharides is an accurate diagnostic test for pneumococcal infection in children with pneumonia in Nepal. Children with pneumococcal pneumonia did not have higher convalescent, or higher fold change, IgG to pneumococcal polysaccharides than children with other causes of pneumonia. Caution is needed in interpreting antibody responses in pneumococcal infections.

Exploiting Vector Pattern Diversity of Molecular Scaffolds for Cheminformatics Tasks in Drug Discovery.

Chemical diversity is challenging to describe objectively. Despite this, various notions of chemical diversity are used throughout the medicinal chemistry optimization process in drug discovery. In this work, we show the usefulness of considering exploited vectors during different phases of the drug design process to provide a quantitative and objective description of chemical diversity. We have developed a concise and fast approach to enumerate and analyze the exploited vector patterns (EVPs) of molecular compound series, which can then be used in archetypal compound selection tasks, from hit matter identification to hit expansion and lead optimization. We first show that EVPs can be used to assess the progressibility of compounds in a fragment library design exercise. By considering EVPs, we then show how a set of compounds can be prioritized for hit expansion using EVP-based, customizable diversity sampling approaches, reducing the time taken and mitigating human biases. We also show that EVPs are a useful tool to analyze SAR data, offering the chance to uncover correlations between different vectors without predetermining the molecular scaffold structures. The codes used to perform these tasks are presented as easy-to-use Jupyter notebooks, which can be readily adapted for further related tasks.

In-hospital mortality trends after surgery for traumatic thoracolumbar injury: A national inpatient sample database study.

Introduction: Given the increasing incidence of traumatic thoracolumbar injuries in recent years, studies have sought to investigate potential risk factors for outcomes in these patients. Research question: The aim of this study was to investigate trends and risk factors for in-hospital mortality after fusion for traumatic thoracolumbar injury. Materials and methods: Patients undergoing thoracolumbar fusion after traumatic injury were queried from the National Inpatient Sample (NIS) from 2012 to 2017. Analysis was performed to identify risk factors for inpatient mortality after surgery. Results: Patients in 2017 were on average older (51.0 vs. 48.5, P = 0.004), had more admitting diagnoses (15.5 vs. 10.7, p < 0.001), were less likely to be White (75.8% vs. 81.2%, p = 0.006), were from a ZIP code with a higher median income quartile (Quartile 1: 31.4% vs. 28.6%, p = 0.011), and were more likely to have Medicare as a primary payer (22.9% vs. 30.1%, p < 0.001). Bivariate analysis of demographics and surgical characteristics demonstrated that patients in the in-hospital mortality group (n = 90) were older (70.2 vs. 49.6, p < 0.001), more likely to be male (74.4% vs. 62.8%, p = 0.031), had a great number of admitted diagnoses (21.3 vs. 12.7, p < 0.001), and were more likely to be insured by Medicare (70.0% vs. 27.0%, p < 0.001). Multivariate regression analysis found age (OR 1.06, p < 0.001) and Black race (OR 3.71, p = 0.007) were independently associated with in-hospital mortality. Conclusion: Our study of nationwide, traumatic thoracolumbar fusion procedures from 2012 to 2017 in the NIS database found older, black patients were at increased risk for in-hospital mortality after surgery.

Optically Transparent Lead Halide Perovskite Polycrystalline Ceramics.

We utilize room-temperature uniaxial pressing at applied loads achievable with low-cost, laboratory-scale presses to fabricate freestanding CH3NH3PbX3 (X- = Br-, Cl-) polycrystalline ceramics with millimeter thicknesses and optical transparency up to ∼70% in the infrared. As-fabricated perovskite ceramics can be produced with desirable form factors (i.e., size, shape, and thickness) and high-quality surfaces without any postprocessing (e.g., cutting or polishing). This method should be broadly applicable to a large swath of metal halide perovskites, not just the compositions shown here. In addition to fabrication, we analyze microstructure-optical property relationships through detailed experiments (e.g., transmission measurements, electron microscopy, X-ray tomography, optical profilometry, etc.) as well as modeling based on Mie theory. The optical, electrical, and mechanical properties of perovskite polycrystalline ceramics are benchmarked against those of single-crystalline analogues through spectroscopic ellipsometry, Hall measurements, and nanoindentation. Finally, γ-ray scintillation from a transparent MAPbBr3 ceramic is demonstrated under irradiation from a 137Cs source. From a broader perspective, scalable methods to produce freestanding polycrystalline lead halide perovskites with comparable properties to their single-crystal counterparts could enable key advancements in the commercial production of perovskite-based technologies (e.g., direct X-ray/γ-ray detectors, scintillators, and nonlinear optics).

Is Oncotype DX testing informative for breast cancers with low ER expression? A retrospective review from a biomarker testing referral center.

PURPOSE: It remains unclear whether patients with HER2-negative, low-estrogen receptor (ER-low)-positive early breast cancer (BC) benefit from Oncotype DX® (ODX) testing. METHODS: We conducted a retrospective review of cases referred for ODX testing over a seven-year period from a breast biomarker testing referral center (n = 854). For each case, we recorded the ODX Recurrence Score (RS) along with percentage of ER nuclear positivity and staining intensity on immunohistochemistry. Our criteria for ER-low was defined as ≤10% cells with nuclear positivity and/or weak intensity of staining. Slides from all ER-low cases were reviewed and the reported ODX ER gene scores were recorded. We randomly selected a comparator group of 56 patients with ER > 10% positivity and non-weak staining intensity (ER-high). RESULTS: We identified 27 cases (3.2%) that met our criteria for ER-low. Of these, 92.6% had a high RS (>25), and 7.4% had a RS of 25. All cases with ≤10% ER nuclear positivity had a high RS. Most ER-low cases (85.2%) had ODX quantitative ER gene scores in the negative range, whereas all (100%) ER-high cases had positive ER gene scores. CONCLUSION: ODX does not appear to add significant additional information to inform treatment decisions for most patients with ER-low BC. Incorporating weak ER staining intensity in addition to low percentage of nuclear positivity identifies about twice as many ER-low patients, although with reduced specificity for high RS. Our study supports the contention that most ER-low early BC should be regarded similarly to ER-negative BC.

Barriers and Unequal Access to Timely Molecular Testing Results: Addressing the Inequities in Cancer Care Delays across Canada.

Genomic medicine is a powerful tool to improve diagnosis and outcomes for cancer patients by facilitating the delivery of the right drug at the right dose at the right time for the right patient. In 2023, a Canadian conference brought together leaders with expertise in different tumor types. The objective was to identify challenges and opportunities for change in terms of equitable and timely access to biomarker testing and reporting at the education, delivery, laboratory, patient, and health-system levels in Canada. Challenges identified included: limited patient and clinician awareness of genomic medicine options with need for formal education strategies; failure by clinicians to discuss genomic medicine with patients; delays in or no access to hereditary testing; lack of timely reporting of results; intra- and inter-provincial disparities in access; lack of funding for patients to access testing and for laboratories to provide testing; lack of standardized testing; and impact of social determinants of health. Canada must standardize its approach to biomarker testing across the country, with a view to addressing current inequities, and prioritize access to advanced molecular testing to ensure systems are in place to quickly bring innovation and evidence-based treatments to Canadian cancer patients, regardless of their place of residence or socioeconomic status.

Flat­Knit, Flexible, Textile Metasurfaces.

Lightweight, low-cost metasurfaces and reflectarrays that are easy to stow and deploy are desirable for many terrestrial and space-based communications and sensing applications. This work demonstrates a lightweight, flexible metasurface platform based on flat-knit textiles operating in the cm-wave spectral range. By using a colorwork knitting approach called float-jacquard knitting to directly integrate an array of resonant metallic antennas into a textile, two textile reflectarray devices, a metasurface lens (metalens), and a vortex-beam generator are realized. Operating as a receiving antenna, the metalens focuses a collimated normal-incidence beam to a diffraction-limited, off-broadside focal spot. Operating as a transmitting antenna, the metalens converts the divergent emission from a horn antenna into a collimated beam with peak measured directivity, gain, and efficiency of 21.30, 15.30, and -6.00 dB (25.12%), respectively. The vortex-beam generating metasurface produces a focused vortex beam with a topological charge of m = 1 over a wide frequency range of 4.1-5.8 GHz. Strong specular reflection is observed for the textile reflectarrays, caused by wavy yarn floats on the backside of the float-jacquard textiles. This work demonstrates a novel approach for the scalable production of flexible metasurfaces by leveraging commercially available yarns and well-established knitting machinery and techniques.

The Relationship Between Uncertainty and Psychological Distress Among Family Caregivers of Patients With Delirium in Intensive Care Units: A Cross-Sectional Survey.

BACKGROUND: Although family caregivers experienced negative psychological symptoms associated with witnessing intensive care unit delirium in their loved ones, there is a lack of clear understanding of how delirium is associated with family caregiver psychological distress. Uncertainty could be a factor contributed to this association. OBJECTIVES: The aim of this study was to examine the relationship between uncertainty and psychological distress among family caregivers of patients with delirium in intensive care units. METHODS: A cross-sectional correlational design was used for this observational study of adult family caregivers of patients admitted to the intensive care unit and who reported witnessing delirium symptoms in their loved ones. Family caregivers completed an electronic survey in January 2022 that consisted of a family caregiver and patient demographic form, the Mishel Uncertainty in Illness Scale-Family Member, and the Kessler Psychological Distress Scale. Descriptive, correlational, and regression statistical analyses were applied. RESULTS: One hundred twenty-one adult family caregivers were enrolled. Family caregivers reported substantial uncertainty (mean, 106.15, on a scale of 31-155) and moderate to severe psychological distress (mean, 31.37, on a scale of 10-50) regarding their witnessing of delirium episodes in their loved ones. Uncertainty was significantly correlated with psychological distress among family caregivers (rs = 0.52, P < .001). Uncertainty significantly predicted psychological distress among family caregivers (regression coefficient, 0.27; P < .001). DISCUSSION: Family caregiver uncertainty was positively associated with psychological distress. This distress can interfere with family caregiver involvement in patient delirium care. These findings are essential to increase critical care nurse awareness and inform the development of nursing interventions to alleviate possible uncertainty and distress.