Surgeon Perceptions of Performing Transforaminal Lumbar Interbody Fusion in an Ambulatory Surgical Center vs Hospital Setting in the Elderly Population: Results of a Surgeon Survey.

BACKGROUND: There is an increasing acceptance of conducting minimally invasive transforaminal lumbar interbody fusion (TLIF) in ambulatory surgical centers (ASCs). The Centers for Medicare and Medicaid Services (CMS) introduced the Hospitals Without Walls (HWW) program in March 2020. This program granted hospitals regulatory flexibility to offer services and procedures in nontraditional locations, including ASCs. However, implementation hurdles persist. METHODS: A survey was sent to 235 surgeons regarding the use of ASCs for performing TLIF surgeries on elderly patients. Multiple-choice questions covering various aspects of TLIF practice preferences, including surgical indications, decision factors for choosing ASCs over hospitals, implementation hurdles, reimbursement concerns, staffing issues, and the impact of CMS rules and regulations on TLIF in ASCs, particularly concerning physician ownership and self-referral conflicts governed by the Stark law, were asked. RESULTS: The survey completion rate was 25.8% (Figure 1). The most common surgical indications for TLIF in ASCs were spondylolisthesis (80%), spinal stenosis (62.5%), and low back pain (47.5%). Most surgeons (78%) believed TLIF could be safely performed in ASCs. Streamlined workflow, lower infection rates, and cost-effectiveness were advantages listed by 58.5% of surgeons. Patient's medical history (75.8%), followed by ASC resources and capabilities (61%) and surgeon preference (61%), were relevant factors. Higher efficiencies at ASCs (14.6%), contractual issues (9.8%), and ownership issues (7.3%) were less relevant to surgeons. About 65.9% of surgeons reported lower reimbursement in ASCs, and 43.9% said it was an implementation hurdle. Lower direct costs were reported by 53.7% of surgeons. Other hurdles included a lack of trained staff (24.4%), inadequate staffing (22.0%), cost overruns (26.8%), high Joint Commission or the Accreditation Association for Ambulatory Health Care credentialing costs, and surgeons feeling uncomfortable performing TLIF in ASCs (22.0%). Only 17.1% listed medical problems as a reason their patient was considered unsuitable for the ASC environment. A majority (53.7%) stated that their ASCs complied with strict Stark requirements by disclosing physician ownership interests. However, 22% of surgeons reported self-referrals under the "In-Office Ancillary Services Exception" allowed by the Stark law. CONCLUSION: Our survey data show that surgeons' perceptions of current CMS rules and regulations may hinder the transition into the ASC setting because they think the reimbursement is too low and the regulatory burden is too high. ASCs have disproportionally higher initial acquisition and ongoing costs related to staff training and maintenance of the TLIF technology that CMS should consider when determining the appropriate financial remuneration for these complex procedures. CLINICAL RELEVANCE: ASC offers a viable and attractive option for their TLIF procedure with the advantage of same-day discharge and at-home recovery.

Multicentre double-blind randomised placebo-controlled trial evaluating the efficacy of the meningococcal B vaccine, 4CMenB (Bexsero), against Neisseria gonorrhoeae infection in men who have sex with men: the GoGoVax study protocol.

INTRODUCTION: Gonorrhoea, the sexually transmissible infection caused by Neisseria gonorrhoeae, has a substantial impact on sexual and reproductive health globally with an estimated 82 million new infections each year worldwide. N. gonorrhoeae antimicrobial resistance continues to escalate, and disease control is largely reliant on effective therapy as there is no proven effective gonococcal vaccine available. However, there is increasing evidence from observational cohort studies that the serogroup B meningococcal vaccine four-component meningitis B vaccine (4CMenB) (Bexsero), licensed to prevent invasive disease caused by Neisseria meningitidis, may provide cross-protection against the closely related bacterium N. gonorrhoeae. This study will evaluate the efficacy of 4CMenB against N. gonorrhoeae infection in men (cis and trans), transwomen and non-binary people who have sex with men (hereafter referred to as GBM+). METHODS AND ANALYSIS: This is a double-blind, randomised placebo-controlled trial in GBM+, either HIV-negative on pre-exposure prophylaxis against HIV or living with HIV (CD4 count >350 cells/mm3), who have had a diagnosis of gonorrhoea or infectious syphilis in the last 18 months (a key characteristic associated with a high risk of N. gonorrhoeae infection). Participants are randomised 1:1 to receive two doses of 4CMenB or placebo 3 months apart. Participants have 3-monthly visits over 24 months, which include testing for N. gonorrhoeae and other sexually transmissible infections, collection of demographics, sexual behaviour risks and antibiotic use, and collection of research samples for analysis of N. gonorrhoeae-specific systemic and mucosal immune responses. The primary outcome is the incidence of the first episode of N. gonorrhoeae infection, as determined by nucleic acid amplification tests, post month 4. Additional outcomes consider the incidence of symptomatic or asymptomatic N. gonorrhoeae infection at different anatomical sites (ie, urogenital, anorectum or oropharynx), incidence by N. gonorrhoeae genotype and antimicrobial resistance phenotype, and level and functional activity of N. gonorrhoeae-specific antibodies. ETHICS AND DISSEMINATION: Ethical approval was obtained from the St Vincent's Hospital Human Research Ethics Committee, St Vincent's Hospital Sydney, NSW, Australia (ref: 2020/ETH01084). Results will be disseminated in peer-reviewed journals and via presentation at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04415424.

Characteristics, outcomes, facilitators and barriers for psychosocial interventions on inpatient mental health dementia wards: a systematic review.

BACKGROUND: The National Institute for Health and Care Excellence guidelines state that psychosocial interventions should be the first line of treatment for people with dementia who are experiencing distress behaviours, such as agitation and depression. However, little is known about the characteristics and outcomes of psychosocial interventions or the facilitators and barriers to implementation on inpatient mental health dementia wards which provide care for people with dementia who are often experiencing high levels of distress. METHODS: A systematic search was conducted on MEDLINE, CINAHL, PsycINFO, Psychology and Behavioural Sciences Collection, and Scopus in May 2023, following PRISMA guidelines. Reference and citation searches were conducted on included articles. Peer-reviewed literature of any study design, relating to psychosocial interventions in inpatient mental health dementia wards, was included. One author reviewed all articles, with a third of results reviewed independently by a second author. Data were extracted to a bespoke form and synthesised using a narrative review. The quality of included studies was appraised using the Mixed Methods Appraisal Tool. RESULTS: Sixteen studies were included in the synthesis, which together included a total of 538 people with dementia. Study methods and quality varied. Psychosocial interventions delivered on wards included music therapy (five studies), multisensory interventions (four studies), multicomponent interventions (two studies), technology-based interventions (two studies), massage interventions (two studies) and physical exercise (one study). Reduction in distress and improvement in wellbeing was demonstrated inconsistently across studies. Delivering interventions in a caring and individualised way responding to patient need facilitated implementation. Lack of staff time and understanding of interventions, as well as high levels of staff turnover, were barriers to implementation. CONCLUSION: This review highlights a striking lack of research and therefore evidence base for the use of psychosocial interventions to reduce distress in this vulnerable population, despite current healthcare guidelines. More research is needed to understand which psychosocial interventions can reduce distress and improve wellbeing on inpatient mental health dementia wards, and how interventions should be delivered, to establish clinical and cost effectiveness and minimise staff burden.

Anatomical Location of the Vesical Branches of the Inferior Hypogastric Plexus in Human Cadavers.

We have demonstrated in canines that somatic nerve transfer to vesical branches of the inferior hypogastric plexus (IHP) can be used for bladder reinnervation after spinal root injury. Yet, the complex anatomy of the IHP hinders the clinical application of this repair strategy. Here, using human cadavers, we clarify the spatial relationships of the vesical branches of the IHP and nearby pelvic ganglia, with the ureteral orifice of the bladder. Forty-four pelvic regions were examined in 30 human cadavers. Gross post-mortem and intra-operative approaches (open anterior abdominal, manual laparoscopic, and robot-assisted) were used. Nerve branch distances and diameters were measured after thorough visual inspection and gentle dissection, so as to not distort tissue. The IHP had between 1 to 4 vesical branches (2.33 ± 0.72, mean ± SD) with average diameters of 0.51 ± 0.06 mm. Vesical branches from the IHP arose from a grossly visible pelvic ganglion in 93% of cases (confirmed histologically). The pelvic ganglion was typically located 7.11 ± 6.11 mm posterolateral to the ureteral orifice in 69% of specimens. With this in-depth characterization, vesical branches from the IHP can be safely located both posterolateral to the ureteral orifice and emanating from a more proximal ganglionic enlargement during surgical procedures.

Comparison of patient-reported outcomes and clinical characteristics among patients with pituitary macroadenomas and giant adenomas.

KEY POINTS: Patients with giant adenomas are more likely to have tumor extension into the paranasal sinuses. Compared to macroadenomas, giant adenomas are not associated with worse preoperative SNOT-22 scores.

Single nucleotide polymorphism (SNP) chromosomal microarray as a diagnostic tool for mucinous tubular and spindle cell carcinoma: A validation study.

Mucinous tubular and spindle cell carcinoma (MTSCC) shows significant overlap with papillary renal cell carcinoma (PRCC), and harbor recurrent copy-number alterations (CNA). We evaluated 16 RCC with features suggestive of MTSCC using chromosomal microarrays. The cohort was comprised of 8 females and males, each, with an age range of 33-79 years (median, 59), and a tumor size range of 3.4-15.5 cm (median, 5.0). Half the tumors were high-grade (8/16, 50%) with features such as necrosis, marked cytologic atypia, and sarcomatoid differentiation, and 5/16 (31%) were high stage (≥pT3a). Three (of 16, 19%) cases had a predominant (>95%) spindle cell component, whereas 5/16 (31%) were composed of a predominant (>95%) epithelial component. Most cases (12/16, 75%) exhibited a myxoid background and/or extravasated mucin, at least focally. Twelve (of 16, 75%) cases demonstrated CNA diagnostic of MTSCC (losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22). In addition, 2 high-grade tumors showed loss of CDKN2A/B, and gain of 1q, respectively, both of which are associated with aggressive behavior. Three (of 16, 19%) cases, demonstrated nonspecific CNA, and did not meet diagnostic criteria for established RCC subtypes. One (of 16, 6%) low-grade epithelial predominant tumor (biopsy) demonstrated characteristic gains of 7, 17, and loss of Y, diagnostic of PRCC. MTSCC can be a morphologically heterogenous tumor. Our study validates the detection of characteristic chromosomal CNA for diagnostic use that may be useful in challenging cases with unusual spindle cell or epithelial predominant features, as well as in high-grade tumors.

Status foe: a psychobiographical investigation of Ida B. Wells.

Ida B. Wells (1862-1931) led an extraordinary life as a journalist, educator, and activist while navigating the intersecting social realities of race, gender, and class. She embodied courage, advocating for the civil rights of Black Americans in an uncompromising fashion.Building on decades of research in social psychology, sociologist Cecilia L. Ridgeway presents (2019) a cultural schema theory of status. She contends that issues of status in interpersonal contexts are an unavoidable aspect of the human condition. Despite the ubiquity of status as a sociocultural force, Ridgeway believes that status hierarchies may be undermined.The present study is a psychobiographical exploration of Wells through the lens of Ridgeway's status theory. It explores: the development of Wells' cultural schemas; how Wells navigated her own status; the inter-relationship between Wells and her sociocultural context; and how Wells undermined and overcame status hierarchies.

Medical Costs of RSV-associated Hospitalizations and Emergency Department Visits in Children Aged <5 years: Observational Findings from the New Vaccine Surveillance Network (NVSN), 2016-2019.

OBJECTIVE: To assess medical costs of hospitalizations and emergency department (ED) care associated with respiratory syncytial virus (RSV) disease in children enrolled in the New Vaccine Surveillance Network. STUDY DESIGN: We used accounting and prospective surveillance data from six pediatric health systems to assess direct medical costs from laboratory-confirmed RSV-associated hospitalizations (n=2,007) and ED visits (n=1,267) from 2016 through 2019 among children aged <5 years. We grouped costs into categories relevant to clinical care and administrative billing practices. We examined RSV-associated medical costs by care setting using descriptive and bivariate analyses. We assessed associations between known RSV risk factors and hospitalization costs and length of stay (LOS) using chi-square tests of association. RESULTS: The median cost was $7,100 (IQR: $4,006-$13,355) per hospitalized child and $503 (IQR: $387-$930) per ED visit. Eighty percent (n=2,628) of our final sample were children aged <2 years. Fewer weeks' gestational age (GA) was associated with higher median costs in hospitalized children [p<0.001, ≥37 weeks' GA: $6,840 ($3,905-$12,450); 29-36 weeks' GA: $7,721 ($4,362-$15,274); <29 w weeks' GA: $9,131 ($4,518-$19,924)]. Full-term infants accounted for 70% of the total expenditures in our sample. Almost three quarters of the healthcare dollars spent originated in children under 12 months of age; the primary age group targeted by recommended RSV prophylactics. CONCLUSIONS: Reducing the cost burden for RSV-associated medical care in young children will require prevention of RSV in all young children, not just high-risk infants. Newly available maternal vaccine and immunoprophylaxis products could substantially reduce RSV-associated medical costs.

Absorption-invariant focusing efficiency for wavefront-shaping controlled reflection from absorbing disordered media.

We numerically model the influence of absorption on wavefront-shaping controlled reflection from absorbing disordered media and provide experimental verification of our model. We find that absorption modifies the reflection eigenvalue density, the average reflectance, and the reflection matrix element density. However, we also find that despite these effects, the efficiency of wavefront-shaping controlled reflection is invariant with absorption.

Non-endothelial expression of Endomucin in the mouse and human choroid.

Endomucin (EMCN) is a 261 AA transmembrane glycoprotein that is highly expressed by venous and capillary endothelial cells where it plays a role in VEGF-mediated angiogenesis and regulation of immune cell recruitment. However, it is better known as a histological marker, where it has become widespread due to the commercial availability of high-quality antibodies that work under a wide range of conditions and in many tissues. The specificity of EMCN staining has been well-validated in retinal vessels, but while it has been used extensively as a marker in other tissues of the eye, including the choroid, the pattern of expression has not been described in detail. Here, in addition to endothelial expression in the choriocapillaris and deeper vascular layers, we characterize a population of EMCN-positive perivascular cells in the mouse choroid that did not co-localize with cells expressing other endothelial markers such as PECAM1 or PODXL. To confirm that these cells represented a new population of EMCN-expressing stromal cells, we then performed single cell RNA sequencing in choroids from adult wild-type mice. Analysis of this new dataset confirmed that, in addition to endothelial cells, Emcn mRNA expression was present in choroidal pericytes and a subset of fibroblasts, but not vascular smooth muscle cells. Besides Emcn , no known endothelial gene expression was detected in these cell populations, confirming that they did not represent endothelial-stromal doublets, a common technical artifact in single cell RNA seq datasets. Instead, choroidal Emcn -expressing fibroblasts exhibited high levels of chemokine and interferon signaling genes, while Emcn -negative fibroblasts were enriched in genes encoding extracellular matrix proteins. Emcn expressing fibroblasts were also detected in published datasets from mouse brain and human choroid, suggesting that stromal Emcn expression was not unique to the choroid and was evolutionarily conserved. Together, these findings highlight unique fibroblast and pericyte populations in the choroid and provide new context for the role of EMCN in angiogenesis and immune cell recruitment.

Trends in the prevalence and pharmacological management of migraine during pregnancy in the UK, 2000-2018.

BACKGROUND: Migraine is common in women of reproductive age. This study aimed to (1) describe the prevalence of migraine in pregnant women in the UK, (2) identify drugs commonly prescribed for migraine during pregnancy and (3) identify characteristics associated with being prescribed medication for migraine during pregnancy. METHODS: The Clinical Practice Research Datalink pregnancy register, a database of pregnancy episodes identified in anonymised primary care health records, was used.Crude and age-standardised prevalence of migraine during pregnancy and the proportion of women with migraine prescribed drugs used for migraine management were calculated for each year between 2000 and 2018.Logistic regression was used to describe the relationship between patient characteristics and being prescribed migraine medication during pregnancy. RESULTS: 1 377 053 pregnancies were included, of which 187 328 were in women with a history of migraine. The age-adjusted prevalence increased from 11.4% in 2000 to 17.2% in 2018. There was an increase in the rates of prescription for numerous medications for the management of migraine.Older women (adjusted OR (aOR) 1.41 (1.20 to 1.66)), women of black (aOR 1.40 (1.32 to 1.48)) and South Asian ethnicity (aOR 1.48 (1.38 to 1.59)), those living in the most deprived areas (aOR 1.60 (1.54 to 1.66)), women who were obese (aOR 1.39 (1.35 to 1.43)), smokers (aOR 1.15 (1.12 to 1.18)) and those with comorbid conditions were more likely to receive a prescription during pregnancy. CONCLUSIONS: Rates of recorded migraine have increased over the past two decades as well as rates of prescribing in women with migraine. Higher prescribing rates are seen in certain groups, which has the potential to exacerbate health inequalities.

Contribution of an alternative 16S rRNA helix to biogenesis of the 30S subunit of the ribosome.

30S subunits become inactive upon exposure to low Mg2+ concentration, due to a reversible conformational change that entails nucleotides (nt) in the neck helix (h28) and 3' tail of 16S rRNA. This active-to-inactive transition involves partial unwinding of h28 and re-pairing of nt 921-923 with nt 1532-1534, which requires flipping of the 3' tail by ~180 degrees. Growing evidence suggests that immature 30S particles adopt the inactive conformation in the cell, and transition to the active state occurs at a late stage of maturation. Here, we target nucleotides that form the alternative helix (hALT) of the inactive state. Using an orthogonal ribosome system, we find that disruption of hALT decreases translation activity in the cell modestly, by ~2-fold, without compromising ribosome fidelity. Ribosomes carrying substitutions at positions 1532-1533 support growth of E. coli strain Δ7 prrn (which carries a single rRNA operon), albeit at rates 10-20% slower than wild-type ribosomes. These mutant Δ7 prrn strains accumulate free 30S particles and precursor 17S rRNA, indicative of biogenesis defects. Analysis of purified control and mutant subunits suggests that hALT stabilizes the inactive state by 1.2 kcal/mol with little-to-no impact on the active state or the transition state of conversion.

Pulmonary Vein Isolation With or Without Left Atrial Appendage Ligation in Atrial Fibrillation: The aMAZE Randomized Clinical Trial.

Importance: Left atrial appendage elimination may improve catheter ablation outcomes for atrial fibrillation. Objective: To assess the safety and effectiveness of percutaneous left atrial appendage ligation adjunctive to catheter pulmonary vein isolation for nonparoxysmal atrial fibrillation. Design, Setting, and Participants: This multicenter, prospective, open-label, randomized clinical trial evaluated the safety and effectiveness of percutaneous left atrial appendage ligation adjunctive to planned pulmonary vein isolation for nonparoxysmal atrial fibrillation present for less than 3 years. Eligible patients were randomized in a 2:1 ratio to undergo left atrial appendage ligation and pulmonary vein isolation or pulmonary vein isolation alone. Use of a 2:1 randomization ratio was intended to provide more device experience and safety data. Patients were enrolled from October 2015 to December 2019 at 53 US sites, with the final follow-up visit on April 21, 2021. Interventions: Left atrial appendage ligation plus pulmonary vein isolation compared with pulmonary vein isolation alone. Main Outcomes and Measures: A bayesian adaptive analysis was used for primary end points. Primary effectiveness was freedom from documented atrial arrythmias of greater than 30 seconds duration 12 months after undergoing pulmonary vein isolation. Rhythm was assessed by Holter monitoring at 6 and 12 months after pulmonary vein isolation, symptomatic event monitoring, or any electrocardiographic tracing obtained through 12 months after pulmonary vein isolation. Primary safety was a composite of predefined serious adverse events compared with a prespecified 10% performance goal 30 days after the procedure. Left atrial appendage closure was evaluated through 12 months after pulmonary vein isolation. Results: Overall, 404 patients were randomized to undergo left atrial appendage ligation plus pulmonary vein isolation and 206 were randomized to undergo pulmonary vein isolation alone. Primary effectiveness was 64.3% with left atrial appendage ligation and pulmonary vein isolation and 59.9% with pulmonary vein isolation only (difference, 4.3% [bayesian 95% credible interval, -4.2% to 13.2%]; posterior superiority probability, 0.835), which did not meet the statistical criterion to establish superiority (0.977). Primary safety was met, with a 30-day serious adverse event rate of 3.4% (bayesian 95% credible interval, 2.0% to 5.0%; posterior probability, 1.0) which was less than the prespecified threshold of 10%. At 12 months after pulmonary vein isolation, complete left atrial appendage closure (0 mm residual communication) was observed in 84% of patients and less than or equal to 5 mm residual communication was observed in 99% of patients. Conclusions and Relevance: Percutaneous left atrial appendage ligation adjunctive to pulmonary vein isolation did not meet prespecified efficacy criteria for freedom from atrial arrhythmias at 12 months compared with pulmonary vein isolation alone for patients with nonparoxysmal atrial fibrillation, but met prespecified safety criteria and demonstrated high rates of closure at 12 months. Trial Registration: ClinicalTrials.gov Identifier: NCT02513797.

Results of an interlaboratory study on the working curve in vat photopolymerization.

The working curve informs resin properties and print parameters for stereolithography, digital light processing, and other photopolymer additive manufacturing (PAM) technologies. First demonstrated in 1992, the working curve measurement of cure depth vs radiant exposure of light is now a foundational measurement in the field of PAM. Despite its widespread use in industry and academia, there is no formal method or procedure for performing the working curve measurement, raising questions about the utility of reported working curve parameters. Here, an interlaboratory study (ILS) is described in which 24 individual laboratories performed a working curve measurement on an aliquot from a single batch of PAM resin. The ILS reveals that there is enormous scatter in the working curve data and the key fit parameters derived from it. The measured depth of light penetration Dp varied by as much as 7x between participants, while the critical radiant exposure for gelation Ec varied by as much as 70x. This significant scatter is attributed to a lack of common procedure, variation in light engines, epistemic uncertainties from the Jacobs equation, and the use of measurement tools with insufficient precision. The ILS findings highlight an urgent need for procedural standardization and better hardware characterization in this rapidly growing field.

Optimization of a mouse model of pancreatic cancer to simulate the human phenotypes of metastasis and cachexia.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) presents with a high mortality rate. Two important features of PDAC contribute to this poor outcome. The first is metastasis which occurs in ~ 80% of PDAC patients. The second is cachexia, which compromises treatment tolerance for patients and reduces their quality of life. Although various mouse models of PDAC exist, recapitulating both metastatic and cachectic features have been challenging. METHODS: Here, we optimize an orthotopic mouse model of PDAC by altering several conditions, including the subcloning of parental murine PDAC cells, implantation site, number of transplanted cells, and age of recipient mice. We perform spatial profiling to compare primary and metastatic immune microenvironments and RNA sequencing to gain insight into the mechanisms of muscle wasting in PDAC-induced cachexia, comparing non-metastatic to metastatic conditions. RESULTS: These modifications extend the time course of the disease and concurrently increase the rate of metastasis to approximately 70%. Furthermore, reliable cachexia endpoints are achieved in both PDAC mice with and without metastases, which is reminiscent of patients. We also find that cachectic muscles from PDAC mice with metastasis exhibit a similar transcriptional profile to muscles derived from mice and patients without metastasis. CONCLUSION: Together, this model is likely to be advantageous in both advancing our understanding of the mechanism of PDAC cachexia, as well as in the evaluation of novel therapeutics.

Evaluating the definition and distribution of spring ephemeral wildflowers in eastern North America.

PREMISE: The herbaceous layer accounts for the majority of plant biodiversity in eastern North American forests, encompassing substantial variation in life history strategy and function. One group of early-season herbaceous understory species, colloquially referred to as spring ephemeral wildflowers, are ecologically and culturally important, but little is known about the prevalence and biogeographic patterns of the spring ephemeral strategy. METHODS: We used observations collected by the Global Biodiversity Information Facility (GBIF) to quantify the ephemerality of 559 understory forb species across eastern North America and classify them according to a continuous ephemerality index (ranging from 0 = never ephemeral to 1 = always ephemeral). We then used this information to model where ephemeral forbs were most common across the landscape with the goal of identifying geographic and environmental drivers important to their distributions and ranges. RESULTS: Only 3.4% of all understory wildflower species were spring ephemerals in all parts of their range, and 18.4% (103 species) were ephemeral in at least part of their range. Spring ephemerals peaked in absolute species richness and relative proportion at mid latitudes. CONCLUSIONS: Spring ephemeral phenology is an important shade-avoidance strategy for a large segment of the total understory species in temperate deciduous forests. In North America, the strategy is relatively most important for forest understories at mid latitudes. The definitions of spring ephemerality we provide here serve as an important ecological context for conservation priorities and to evaluate responses of this biodiverse group to future environmental change.

SleepInvestigatoR: A flexible R function for analyzing scored sleep in rodents.

Analyzing scored sleep is a fundamental prerequisite to understanding how sleep changes between health and disease. Classically, this is accomplished by manually calculating various measures (e.g., percent of non-rapid eye movement sleep) from a collection of scored sleep files. This process can be tedious and error prone especially when studies include a large number of animals or involve long recording sessions. To address this issue, we present SleepInvestigatoR, a versatile tool that can quickly organize and analyze multiple scored sleep files into a single output. The function is written in the open-source statistical language R and has a total of 25 parameters that can be set to match a wide variety of experimenter needs. SleepInvestigatoR delivers a total of 22 unique measures of sleep, including all measures commonly reported in the rodent literature. A simple plotting function is also provided to quickly graph and visualize the scored data. All code is designed to be implemented with little formal coding knowledge and step-by-step instructions are provided on the corresponding GitHub page. Overall, SleepInvestigatoR provides the sleep researcher a critical tool to increase efficiency, interpretation, and reproducibility in analyzing scored rodent sleep.

Clinical and Radiographic Outcomes of Shoulder Hemiarthroplasty for Patients with Glenoid Medialization.

BACKGROUND: Glenoid bone loss in shoulder arthroplasty is a difficult problem that is prone to complications due to challenges with achieving glenoid component fixation and stability. The purpose of this study was to evaluate the outcomes of primary shoulder hemiarthroplasty for patients with severe glenoid medialization precluding placement of a glenoid component. METHODS: This was a retrospective case series evaluating patients who underwent shoulder hemiarthroplasty for severe glenoid erosion and medialization between 2010 and 2020. Patients were evaluated via chart review and phone survey to determine if there were any reoperations at final follow-up and to obtain Single Assessment Numeric Evaluation (SANE), American Shoulder and Elbow Surgeons (ASES), and Simple Shoulder Test (SST) scores. Preoperative and postoperative radiographs were evaluated and compared to determine glenoid morphology, version, medialization, acromiohumeral distance, and humeral offset. Final postoperative films were also evaluated for anterosuperior migration and signs of mechanical failure including loosening or periprosthetic fracture. RESULTS: Overall, there were 28 patients during this period who underwent shoulder hemiarthroplasty for severe glenoid medialization. Eight patients were deceased at the time of the study, 2 were unable to complete surveys due to dementia, and 7 were lost to follow-up. The final cohort included 11 shoulders and 11 patients with mean age of 71 +/- 7.1 years and mean follow-up of 6.7 years (range 1.6 - 13.0 years). Mean postoperative SANE, ASES, and SST scores were 80.6 +/- 17.6, 71.5 +/- 29.3, and 7.6 +/- 2.0, respectively. There were no reoperations or revision surgeries at final follow-up. Radiographic evaluation demonstrated severe glenoid medialization and decreased lateral humeral offset which was unchanged postoperatively. There were 2 patients with signs of anterosuperior migration at final radiographic follow-up but no signs of implant failure. CONCLUSION: Shoulder hemiarthroplasty for severe medial glenoid bone loss provides modest clinical outcomes and low rates of reoperation at mid to long term follow-up and is an option worth considering in cases where placement of a glenoid component is challenging due to deficient bone stock and high risk for complications.

Synthetic cationic helical polypeptides for the stimulation of antitumour innate immune pathways in antigen-presenting cells.

Intracellular DNA sensors regulate innate immunity and can provide a bridge to adaptive immunogenicity. However, the activation of the sensors in antigen-presenting cells (APCs) by natural agonists such as double-stranded DNAs or cyclic nucleotides is impeded by poor intracellular delivery, serum stability, enzymatic degradation and rapid systemic clearance. Here we show that the hydrophobicity, electrostatic charge and secondary conformation of helical polypeptides can be optimized to stimulate innate immune pathways via endoplasmic reticulum stress in APCs. One of the three polypeptides that we engineered activated two major intracellular DNA-sensing pathways (cGAS-STING (for cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes) and Toll-like receptor 9) preferentially in APCs by promoting the release of mitochondrial DNA, which led to the efficient priming of effector T cells. In syngeneic mouse models of locally advanced and metastatic breast cancers, the polypeptides led to potent DNA-sensor-mediated antitumour responses when intravenously given as monotherapy or with immune checkpoint inhibitors. The activation of multiple innate immune pathways via engineered cationic polypeptides may offer therapeutic advantages in the generation of antitumour immune responses.