A Systematic Review and Meta-Analysis of the Pathology Underlying Aneurysm Enhancement on Vessel Wall Imaging.

Intracranial aneurysms are common, but only a minority rupture and cause subarachnoid haemorrhage, presenting a dilemma regarding which to treat. Vessel wall imaging (VWI) is a contrast-enhanced magnetic resonance imaging (MRI) technique used to identify unstable aneurysms. The pathological basis of MR enhancement of aneurysms is the subject of debate. This review synthesises the literature to determine the pathological basis of VWI enhancement. PubMed and Embase searches were performed for studies reporting VWI of intracranial aneurysms and their correlated histological analysis. The risk of bias was assessed. Calculations of interdependence, univariate and multivariate analysis were performed. Of 228 publications identified, 7 met the eligibility criteria. Individual aneurysm data were extracted for 72 out of a total of 81 aneurysms. Univariate analysis showed macrophage markers (CD68 and MPO, p = 0.001 and p = 0.002), endothelial cell markers (CD34 and CD31, p = 0.007 and p = 0.003), glycans (Alcian blue, p = 0.003) and wall thickness (p = 0.030) were positively associated with enhancement. Aneurysm enhancement therefore appears to be associated with inflammatory infiltrate and neovascularisation. However, all these markers are correlated with each other, and the literature is limited in terms of the numbers of aneurysms analysed and the parameters considered. The data are therefore insufficient to determine if these associations are independent of each other or of aneurysm size, wall thickness and rupture status. Thus, the cause of aneurysm-wall enhancement currently remains unknown.

Clinical impact of anti-inflammatory microglia and macrophage phenotypes at glioblastoma margins.

Glioblastoma is a devastating brain cancer for which effective treatments are required. Tumour-associated microglia and macrophages promote glioblastoma growth in an immune-suppressed microenvironment. Most recurrences occur at the invasive margin of the surrounding brain, yet the relationships between microglia/macrophage phenotypes, T cells and programmed death-ligand 1 (an immune checkpoint) across human glioblastoma regions are understudied. In this study, we performed a quantitative immunohistochemical analysis of 15 markers of microglia/macrophage phenotypes (including anti-inflammatory markers triggering receptor expressed on myeloid cells 2 and CD163, and the low-affinity-activating receptor CD32a), T cells, natural killer cells and programmed death-ligand 1, in 59 human IDH1-wild-type glioblastoma multi-regional samples (n = 177; 1 sample at tumour core, 2 samples at the margins: the infiltrating zone and leading edge). Assessment was made for the prognostic value of markers; the results were validated in an independent cohort. Microglia/macrophage motility and activation (Iba1, CD68), programmed death-ligand 1 and CD4+ T cells were reduced, and homeostatic microglia (P2RY12) were increased in the invasive margins compared with the tumour core. There were significant positive correlations between microglia/macrophage markers CD68 (phagocytic)/triggering receptor expressed on myeloid cells 2 (anti-inflammatory) and CD8+ T cells in the invasive margins but not in the tumour core (P < 0.01). Programmed death-ligand 1 expression was associated with microglia/macrophage markers (including anti-inflammatory) CD68, CD163, CD32a and triggering receptor expressed on myeloid cells 2, only in the leading edge of glioblastomas (P < 0.01). Similarly, there was a positive correlation between programmed death-ligand 1 expression and CD8+ T-cell infiltration in the leading edge (P < 0.001). There was no relationship between CD64 (a receptor for autoreactive T-cell responses) and CD8+/CD4+ T cells, or between the microglia/macrophage antigen presentation marker HLA-DR and microglial motility (Iba1) in the tumour margins. Natural killer cell infiltration (CD335+) correlated with CD8+ T cells and with CD68/CD163/triggering receptor expressed on myeloid cells 2 anti-inflammatory microglia/macrophages at the leading edge. In an independent large glioblastoma cohort with transcriptomic data, positive correlations between anti-inflammatory microglia/macrophage markers (triggering receptor expressed on myeloid cells 2, CD163 and CD32a) and CD4+/CD8+/programmed death-ligand 1 RNA expression were validated (P < 0.001). Finally, multivariate analysis showed that high triggering receptor expressed on myeloid cells 2, programmed death-ligand 1 and CD32a expression at the leading edge were significantly associated with poorer overall patient survival (hazard ratio = 2.05, 3.42 and 2.11, respectively), independent of clinical variables. In conclusion, anti-inflammatory microglia/macrophages, CD8+ T cells and programmed death-ligand 1 are correlated in the invasive margins of glioblastoma, consistent with immune-suppressive interactions. High triggering receptor expressed on myeloid cells 2, programmed death-ligand 1 and CD32a expression at the human glioblastoma leading edge are predictors of poorer overall survival. Given substantial interest in targeting microglia/macrophages, together with immune checkpoint inhibitors in cancer, these data have major clinical implications.

Spinal anaplastic ganglioglioma.

Anaplastic gangliogliomas of the spinal cord are extremely rare with only four cases reported in the literature. Here we present the case of a 22-year-old female who presented acutely with quadraparesis and urinary retention. Radiographic imaging demonstrated an intramedullary lesion within the cervical spine. She underwent a cervical laminectomy and resection of the lesion under neurophysiological monitoring. Post-operatively, she regained some function, but remained paraparetic. Histopathology demonstrated an anaplastic ganglioglioma (WHO Grade 3). She subsequently underwent radiotherapy. Following surgery, she remained stable and had MRC Grade 3 Power in all four limbs. Herein, we describe a previously undescribed case of cervical anaplastic ganglioglioma and review the existing literature.

Subjective well-being during the 2020-21 global coronavirus pandemic: Evidence from high frequency time series data.

We investigate how subjective well-being varied over the course of the global COVID-19 pandemic, with a special attention to periods of lockdown. We use weekly data from YouGov's Great Britain Mood Tracker Poll, and daily reports from Google Trends, that cover the entire period from six months before until eighteen months after the global spread of COVID-19. Descriptive trends and time-series models suggest that negative mood associated with the imposition of lockdowns returned to baseline within 1-3 weeks of lockdown implementation, whereas pandemic intensity, measured by the rate of fatalities from COVID-19 infection, was persistently associated with depressed affect. The results support the hypothesis that country-specific pandemic severity was the major contributor to increases in negative affect observed during the COVID-19 pandemic, and that lockdowns likely ameliorated rather than exacerbated this effect.

Aspergillus fumigatus causing vertebral osteomyelitis in an immunocompetent patient: a case report and literature review.

Aspergillus vertebral osteomyelitis causing deformity in immunocompetent patients is uncommon. We describe a previously healthy 68-year-old male who was referred after 2 years of lower thoracic back pain and gibbus. His inflammatory markers and HIV test were normal. Imaging demonstrated bony destruction of T12/L1 and L2 with vertebral collapse. Following inconclusive CT-guided biopsy, he underwent reconstructive spinal surgery. Histopathology showed fungi and Aspergillus fumigatus was cultured. He was treated with isavuconazole 200 mg once daily for 12 months with a satisfactory clinical outcome. We present a summary of recently published cases of atraumatic Aspergillus vertebral osteomyelitis in immunocompetent patients without risk factors. Fungal infection should be considered in culture-negative spondylodiscitis, even in the absence of risk factors.

Scale Norming Undermines the Use of Life Satisfaction Scale Data for Welfare Analysis.

Scale norming is where respondents use qualitatively different scales to answer the same question across survey waves. It makes responses challenging to compare intertemporally or interpersonally. This paper develops a formal model of the cognitive process that could give rise to scale norming in year on year responses to life satisfaction scale questions. It then uses this model to conceptually differentiate scale norming from adaptation and changes in reference points. Scale norming could make life satisfaction responses misleading with regards to the changing welfare of individuals. In particular, individuals who would say that their life is "improving" or "going well" might nonetheless give the same scale response year after year. This has negative implications for the use of scales in cost-benefit analysis and other welfarist applications. While there is already substantial empirical evidence for the existence of scale norming, its implications for welfare analysis are sometimes understated on the grounds that this evidence might simply be the product of errors of memory. The paper presents new empirical evidence for scale norming from two surveys (N1 = 278; N2 = 1050) designed such that errors of memory are an unconvincing explanation for the results.

Be Happy: Navigating Normative Issues in Behavioral and Well-Being Public Policy.

Psychological science is increasingly influencing public policy. Behavioral public policy (BPP) was a milestone in this regard because it influenced many areas of policy in a general way. Well-being public policy (WPP) is emerging as a second domain of psychological science with general applicability. However, advocacy for WPP is criticized on ethical and political grounds. These criticisms are reminiscent of those directed at BPP over the past decade. This déjà vu suggests the need for interdisciplinary work that establishes normative principles for applying psychological science in public policy. We try to distill such principles for WPP from the normative debates over BPP. We argue that the uptake of BPP by governments was a function of its relatively strong normative and epistemic foundations in libertarian paternalism, or nudging, for short. We explain why the nudge framework is inappropriate for WPP. We then analyze how boosts offer a strict but feasible alternative framework for substantiating the legitimacy of well-being and behavioral policies. We illuminate how some WPPs could be fruitfully promoted as boosts and how they might fall short of the associated criteria.

Intracranial Masson Lesion Following Stereotactic Radiosurgery for Treatment of Intracranial Arteriovenous Malformations.

OBJECTIVES: Masson tumor or intravascular papillary endothelial cell proliferation was first described in 1923. Only a few cases of intracranial Masson tumor have been reported following stereotactic radiosurgery (SRS). We report a series of 6 cases, age range 28-56 years, with intracranial Masson tumor following SRS for treatment of an intracranial arteriovenous malformation (AVM). METHODS: We performed a retrospective case note review, reviewed the imaging, SRS records, and neuropathology specimens following surgical excision. RESULTS: In our series all patients received Leksell SRS with the periphery of the AVM receiving doses ranging from 22-25 Gy. The time lapse from SRS to a clear enhancing mass appearing on imaging ranged from 5-10 years. Four patients underwent craniotomy and excision of the enhancing lesion for persistent edema and an enlarging cyst resulting in a resolution of symptoms. CONCLUSIONS: SRS is an effective treatment for obliteration of intracranial AVMs.

Novel compounds with potent CDK9 inhibitory activity for the treatment of myeloma.

Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the regulation of the cell cycle. The aim of our study was originally the further development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A series of new 2,4-disubstituted pyrimidine derivatives were synthesized around the original hit, but their PLK1 inhibitory activity was very poor. However the novel compounds showed nanomolar CDK9 inhibitory activity and very good antiproliferative effect on multiple myeloma cell lines (RPMI-8226).

Bioretention column study of bacteria community response to salt-enriched artificial stormwater.

Cold climate cities with green infrastructure depend on soil bacteria to remove nutrients from road salt-enriched stormwater. Our research examined how bacterial communities in laboratory columns containing bioretention media responded to varying concentrations of salt exposure from artificial stormwater and the effect of bacteria and salt on column effluent concentrations. We used a factorial design with two bacteria treatments (sterile, nonsterile) and three salt concentrations (935, 315, and 80 ppm), including a deionized water control. Columns were repeatedly saturated with stormwater or deionized and then drained throughout 5 wk, with the last week of effluent analyzed for water chemistry. To examine bacterial communities, we extracted DNA from column bioretention media at time 0 and at week 5 and used molecular profiling techniques to examine bacterial community changes. We found that bacterial community taxa changed between time 0 and week 5 and that there was significant separation between taxa among salt treatments. Bacteria evenness was significantly affected by stormwater treatment, but there were no differences in bacterial richness or diversity. Soil bacteria and salt treatments had a significant effect on the effluent concentration of NO, PO, Cu, Pb, and Zn based on ANOVA tests. The presence of bacteria reduced effluent NO and Zn concentrations by as much as 150 and 25%, respectively, while having a mixed effect on effluent PO concentrations. Our results demonstrate how stormwater can affect bacterial communities and how the presence of soil bacteria improves pollutant removal by green infrastructure.