Objective

Women are under-represented in academia. Causative factors include challenges of career-family integration. We evaluated factors reflecting institutional culture (promotion, retention, hiring, and biasing language in promotion letters) as part of an intervention to help shift culture and raise awareness of flexibility policies at the University of California, Davis (UCD).

Materials and methods

Data on faculty use of family-friendly policies were obtained at baseline, and surveys for policy awareness were conducted pre(2010)/post(2013) an NIH-funded study educational intervention. Data on hires, separations, and promotions were obtained pre(2007-2009, 2234 person-year data points)/post(2010-2012, 2384 person-year data points) intervention and compared by logistic regression and for gender differences. Department promotion letters (53) were also analyzed for biasing language.

Results

Policy use was overall low, highest for female assistant professors, and for maternity leave. Awareness significantly increased for all policies postintervention. Promotions decreased, likely because of increases in advancement deferrals or tenure clock extensions. Pre/postintervention, female and male hires were near parity for assistant professors, but female hires were substantially lower than males for associate (54% less likely, p = 0.03) and full professors (70% less likely, p = 0.002). Once hired, women were no more likely to separate than men. Fewer associate/full professors separated than assistant professors (p = 0.002, p < 0.001, respectively), regardless of gender. Language in promotion letters was not gender biased.

Conclusions

We demonstrate a shift at UCD toward a culture of work-life flexibility, an environment in which letters of recommendation show very few biased descriptions, and in which assistant professor hiring is gender equitable. At the same time, a decrease in number of faculty members applying for promotion and an imbalance of men over women at senior hires independent of policy awareness may challenge the assumption that family-friendly policies, while promoting flexibility, also have a positive impact on professional advancement.

Neurofibromatosis type 1 (NF1) is an inherited tumor syndrome caused by heterozygous germline mutations in the NF1 gene, occurring in approximately 1/2600 individuals. A subset of patients with neurofibromatosis type 1 (NF1) develop juvenile xanthogranulomas (JXGs), a non-Langerhans cell histiocytosis, and some of these patients also develop juvenile myelomonocytic leukemia (JMML).Yet, these associations are poorly delineated.JXG is a benign proliferation of non-Langerhans cells histiocytes characterized by small yellow/brown papulonodules ranging from 1-20 mm in size. JMML is a mixed myeloproliferative-myelodysplastic disorder that affects children, most often before age 6.4. The first and only systematic review on this described therisk of developing JMML 20 to 30 times higher in patients with NF1 with JXG lesions compared to those without JXG. Since then, mostly isolated case reports have either refuted or confirmed this triple association.

A common problem in the assessment of Ki67 proliferative index in well-differentiated gastrointestinal neuroendocrine tumors is distinguishing tumor from non-tumor. This is because background stromal lymphocytes, entrapped non-neoplastic glands, and the delicate vascular network characteristic of neuroendocrine tumors frequently contain a subset of proliferating cells. Furthermore, in small biopsies, crush and cautery artifact can alter the morphologic appearance of tumor cells, making the Ki67 proliferative index more difficult to assess. To address these issues, we developed a synaptophysin-Ki67 double stain using a commercially available immunohistochemistry kit, allowing simultaneous visualization of tumor and proliferating nuclei. To test this method, three gastrointestinal pathologists individually graded 50 gastrointestinal neuroendocrine tumors first using synaptophysin-Ki67 double-stained slides and then, after a washout period, using Ki67-only stained slides (along with routine hematoxylin- and eosin-stained slides). Interobserver agreement on Ki67 proliferative index was moderate using the Ki67-only stained slides (intraclass correlation 0.51, 95% confidence interval: 0.35-0.66) and improved using the synaptophysin-Ki67 double stain (intraclass correlation 0.79, 95% confidence interval: 0.69-0.86). Similarly, interobserver agreement on tumor grade was fair with Ki67-only stained slides (κ=0.39, P<0.001) and improved with the double stain (κ=0.58, P<0.001). Analysis of individual pathologists' scores revealed that fewer total number of tumor cells counted correlated with higher grade designation and appeared to contribute to grade discordance. In tumors cited as particularly challenging to assess by the pathologists, three of four tumors were grade discordant with the Ki67-only stain, whereas all four tumors were grade concordant with the synaptophysin-Ki67 stain. The synaptophysin-Ki67 double stain is the first technique to address specifically the histomorphologic challenges of evaluating Ki67 proliferative index in well-differentiated gastrointestinal neuroendocrine tumors. Although further validation is needed, this study provides evidence that the synaptophysin-Ki67 double stain can improve interobserver agreement.

An extended-release formulation of the NSAID meloxicam (MSR) is used to provide 72 h of continuous analgesia in many species, including rodents. Although standard formulations of meloxicam are frequently used in rats with no observable injection-site reactions, the potential adverse effects from MSR have not been characterized sufficiently nor has a prospective study of these effects been performed in rats. To address this deficiency, we evaluated injection-site reactions after a single subcutaneous administration of MSR (n = 16) or sterile saline (SC, n = 6) in the flank of age- and sex-matched Sprague-Dawley rats. Mass and erythema scores were measured daily for 2 wk, and injection sites were collected for histopathology after euthanasia. Rats were randomly selected for euthanasia at 7 d (n = 12) or 14 d (n = 10) after injection to capture the subacute and chronic phases of mass and erythematic lesion formation. No rats in the SC group developed lesions, whereas all 16 MSR-treated rats developed masses. The median time to first mass in the MSR treatment group was 3 d (95% CI, 2-3 d), and nearly 8 d for erythema (95% CI, 6.7-9.1 d). The trajectory of mass lesion severity showed rapid progression from score 1 at onset (day 2 or 3) to score 2 for almost all animals by day 5 or 6. Histopathology was characterized by localized inflammation with central necrosis and peripheral fibrosis, with some sections showing developing draining tracts. Given the high prevalence and severity of localized skin reactions, MSR analgesia should be considered carefully for Sprague-Dawley rats.

Object

The authors analyzed headache relief after anterior cervical discectomy. Headache may be relieved after anterior cervical discectomy, but the mechanism is unknown. If headaches were directly referred from upper cervical pathology, more headache relief would be expected from surgery performed at higher cervical levels. If spinal kinesthetics were the mechanism, then headache relief may differ between arthroplasty and fusion. Headache relief after anterior cervical discectomy was quantified by the operated disc level and by the method of operation (arthroplasty vs arthrodesis).

Methods

The authors performed a post hoc analysis of an artificial disc trial. Data on headache pain were extracted from the Neck Disability Index (NDI) questionnaire.

Results

A total of 260 patients underwent single-level arthroplasty or arthodesis. Preoperatively, 52% reported NDI headache scores of 3 or greater, compared with only 13%-17% postoperatively. The model-based mean NDI headache score at baseline was 2.5 (95% CI 2.3-2.7) and was reduced by 1.3 points after surgery (95% CI 1.2-1.4, p < 0.001). Higher cervical levels were associated with a greater degree of preoperative headache, but there was no association with headache relief. There was no significant difference in headache relief between arthroplasty and arthrodesis.

Conclusions

Most patients with symptomatic cervical spondylosis have headache as a preoperative symptom (88%). Anterior cervical discectomy with both arthroplasty and arthrodesis is associated with a durable decrease in headache. Headache relief is not related to the level of operation. The mechanism for headache reduction remains unclear.

BACKGROUND: Surveys have found concerningly high levels of agreement that the United States will experience civil war soon. This study assesses variation in expectation of and perceived need for civil war with respondent sociopolitical characteristics, beliefs, firearm ownership, and willingness to engage in political violence. METHODS: Findings are from Wave 2 of a nationally representative annual longitudinal survey of members of the Ipsos KnowledgePanel, conducted May 18-June 8, 2023. All respondents to 2022s Wave 1 who remained in KnowledgePanel were invited to participate. Outcomes are expressed as weighted proportions and adjusted prevalence differences, with p-values adjusted for the false discovery rate and reported as q-values. RESULTS: The completion rate was 84.2%; there were 9385 respondents. After weighting, half the sample was female (50.7%, 95% CI 49.4%, 52.1%); the weighted mean (± standard deviation) age was 48.5 (25.9) years. Approximately 1 respondent in 20 (5.7%, 95% CI 5.1%, 6.4%) agreed strongly or very strongly that in the next few years, there will be civil war in the United States. About 1 in 25 (3.8%, 95% CI 3.2%, 4.4%), and nearly 40% (38.4%, 95% CI 32.3%, 44.5%) of those who strongly or very strongly agreed that civil war was coming, also agreed strongly or very strongly that the United States needs a civil war to set things right. Expectation of and perceived need for civil war were higher among subsets of respondents who in Wave 1 were more willing than others to commit political violence, including MAGA Republicans, persons in strong agreement with racist beliefs or statements of the potential need for violence to effect social change, persons who strongly approved of specified extreme right-wing political organizations and movements, firearm owners who purchased firearms in 2020 or later, and firearm owners who carried firearms in public all or nearly all the time. CONCLUSIONS: In 2023, the expectation that civil war was likely and the belief that it was needed were uncommon but were higher among subsets of the population that had previously been associated with greater willingness to commit political violence. These findings can help guide prevention efforts.

Early diagnosis of melanoma is crucial to improved patient survival. Some melanomas can be difficult to diagnose from histopathology alone, and inter-observer disagreement among dermatopathologists in 15-35% of cases1 can delay diagnosis. PRAME (PReferentially expressed Antigen in MElanoma) is a tumorassociated antigen found to be overexpressed in human melanomas, making it a helpful tool in differentiating between benign vs. malignant melanocytic lesions. PRAME immunohistochemistry (IHC) has been used increasingly in dermatopathology practice, but there is currently no single biomarker or IHC stain that is diagnostic when used alone. S100A8 is a calcium-binding protein found to be highly expressed in certain inflammatory conditions and human cancers2,3. It was recently found by Kiuru et al. to be expressed by the keratinocyte microenvironment of melanomas but not that of melanocytic nevi4 , suggesting its role as a melanoma biomarker. The diagnostic utility of S100A8 IHC when compared to other commonly used melanoma biomarkers, including PRAME, has not yet been assessed. The objective of this study was to compare S100A8 immunohistochemistry with PRAME immunohistochemistry in benign and malignant melanocytic tumors to determine the diagnostic utility of S100A8. 

The sustained-release formulation of meloxicam (MSR) is a compounded NSAID that may provide pain relief for as long as 72 h after administration. MSR injection-site skin reactions have occurred in several species but have not previously been observed in mice. We investigated the development and progression of localized skin reactions after a single injection of MSR in Crl:CD1(ICR), C57BL/6J, and BALB/cJ mice. Each mouse received a subcutaneous injection of MSR (n = 60), standard-formulation meloxicam (MEL; n = 24) or saline (control; SC; n = 24) and was scored daily according to a 5-point system for erythema and mass characteristics. Mice were euthanized at either 7 or 14 d after injection and underwent postmortem analysis. MSR-treated mice had more erythematous and mass reactions than did MEL and SC mice. Mass lesions developed in 49 MSR mice (82%; 95% CI, 70% to 90%), 5 MEL animals (21%; 95% CI, 7% to 42%), and 1 SC mouse. MSR-treated BALB/cJ developed erythematous lesions less frequently than similarly treated Crl:CD1(ICR) or C57BL/6J. Lesions often were ventrolateral to the injection site. The median times to the appearance of mass and erythematous lesions were 2 d and 3 d, respectively. Histologically, the erythematous and mass reactions correlated with necrotizing to pyogranulomatous injection-site panniculitis. Inflammation severity scores at 7 and 14 d after injection were greater in the MSR-treated group than the other 2 groups. No strain- or sex-associated differences emerged except that inflammation severity scores at day 14 were higher in Crl:CD1(ICR) females than males. The character of the inflammatory response in MSR-treated mice did not differ between 7 and 14 d after injection, indicating that MSR-induced inflammation is slow to resolve. The ventral migration and delayed onset of MSR injection-site reactions could result in their being attributed to another cause or not being identified. Researchers and clinicians should be aware of the potential for slowly resolving injection-site reactions with MSR.

Introduction

Cytotoxic chemotherapy might prime urothelial cancer (UC) to checkpoint inhibition, prompting a trial of chemotherapy with the programmed death receptor-1 inhibitor pembrolizumab.

Patients and methods

Patients with advanced, platinum-refractory UC received pembrolizumab and either docetaxel (arm A) or gemcitabine (arm B). Primary end points were assessments of maximum tolerated dose and dose-limiting toxicity (DLT). Secondary end points were overall response rate (ORR) and progression-free survival (PFS).

Results

Twelve patients were enrolled in the initial cohorts; 6 in each arm. One DLT was seen in each arm: Grade 3 hypophosphatemia (arm A), Grade 3 diarrhea (arm B). Adverse events of Grade >3 were observed in 7 (54%), the most common being anemia (6; 50%), fatigue (6; 50%), hyponatremia (4; 33%) and neutropenia (3; 25%), with no treatment-related deaths. There were 5 confirmed responses (1 complete, 4 partial), with an ORR of 42% and disease control rate (DCR) of 58%. Arm A had an ORR of 50% and DCR of 67%, whereas arm B had an ORR of 33% and DCR of 50%. Median PFS was 4.8, 5.7, and 3.7 months for the overall cohort, arm A, and arm B, respectively.

Conclusion

Pembrolizumab with either docetaxel or gemcitabine is feasible for treatment of platinum-refractory advanced UC patients. Preliminary efficacy was observed. Further examination is warranted.