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Objective: Social determinants of health, including the effects of neighborhood disadvantage, impact epilepsy prevalence, treatment, and outcomes. This study characterized the association between aberrant white matter connectivity in temporal lobe epilepsy (TLE) and disadvantage using a US census‐based neighborhood disadvantage metric, the Area Deprivation Index (ADI), derived from measures of income, education, employment, and housing quality. Methods: Participants including 74 TLE patients (47 male, mean age = 39.2 years) and 45 healthy controls (27 male, mean age = 31.9 years) from the Epilepsy Connectome Project were classified into ADI‐defined low and high disadvantage groups. Graph theoretic metrics were applied to multishell connectome diffusion‐weighted imaging (DWI) measurements to derive 162 × 162 structural connectivity matrices (SCMs). The SCMs were harmonized using neuroCombat to account for interscanner differences. Threshold‐free network‐based statistics were used for analysis, and findings were correlated with ADI quintile metrics. A decrease in cross‐sectional area (CSA) indicates reduced white matter integrity. Results: Sex‐ and age‐adjusted CSA in TLE groups was significantly reduced compared to controls regardless of disadvantage status, revealing discrete aberrant white matter tract connectivity abnormalities in addition to apparent differences in graph measures of connectivity and network‐based statistics. When comparing broadly defined disadvantaged TLE groups, differences were at trend level. Sensitivity analyses of ADI quintile extremes revealed significantly lower CSA in the most compared to least disadvantaged TLE group. Significance: Our findings demonstrate (1) the general impact of TLE on DWI connectome status is larger than the association with neighborhood disadvantage; however, (2) neighborhood disadvantage, indexed by ADI, revealed modest relationships with white matter structure and integrity on sensitivity analysis in TLE. Further studies are needed to explore this relationship and determine whether the white matter relationship with ADI is driven by social drift or environmental influences on brain development. Understanding the etiology and course of the disadvantage–brain integrity relationship may serve to inform care, management, and policy for patients. [ABSTRACT FROM AUTHOR]

Rhinoviruses (RVs) can cause severe wheezing illnesses in young children and patients with asthma. Vaccine development has been hampered by the multitude of RV types with little information about cross‐neutralization. We previously showed that neutralizing antibody (nAb) responses to RV‐C are detected twofold to threefold more often than those to RV‐A throughout childhood. Based on those findings, we hypothesized that RV‐C infections are more likely to induce either cross‐neutralizing or longer‐lasting antibody responses compared with RV‐A infections. We pooled RV diagnostic data from multiple studies of children with respiratory illnesses and compared the expected versus observed frequencies of sequential infections with RV‐A or RV‐C types using log‐linear regression models. We tested longitudinally collected plasma samples from children to compare the duration of RV‐A versus RV‐C nAb responses. Our models identified limited reciprocal cross‐neutralizing relationships for RV‐A (A12–A75, A12–A78, A20–A78, and A75–A78) and only one for RV‐C (C2–C40). Serologic analysis using reference mouse sera and banked human plasma samples confirmed that C40 infections induced nAb responses with modest heterotypic activity against RV‐C2. Mixed‐effects regression modeling of longitudinal human plasma samples collected from ages 2 to 18 years demonstrated that RV‐A and RV‐C illnesses induced nAb responses of similar duration. These results indicate that both RV‐A and RV‐C nAb responses have only modest cross‐reactivity that is limited to genetically similar types. Contrary to our initial hypothesis, RV‐C species may include even fewer cross‐neutralizing types than RV‐A, whereas the duration of nAb responses during childhood is similar between the two species. The modest heterotypic responses suggest that RV vaccines must have a broad representation of prevalent types. [ABSTRACT FROM AUTHOR]

In the wake of new academic and government attention paid to China's growing Arctic security interests, this article examines the strategic advantages which may lead China to deploy submarines into the polar waters as well as the disadvantages and dangers inherent in such a mission. In contrast to the general belief that such an under-ice presence is both imminent and dangerous to the US and its allies, this piece suggests a more nuanced appreciation for the limited value of the Arctic as a realm of Sino-American competition. [ABSTRACT FROM AUTHOR]

Rationale: Rhinovirus (RV) C can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing.Objectives: To identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses.Methods: Longitudinal data from the COAST (Childhood Origins of Asthma) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for RV-A and RV-C (three types each) were determined using a novel PCR-based assay. Data were pooled from 14 study cohorts in the United States, Finland, and Australia, and mixed-effects logistic regression was used to identify factors related to the proportion of RV-C versus RV-A detection.Measurements and Main Results: In COAST, RV-A and RV-C infections were similarly common in infancy, whereas RV-C was detected much less often than RV-A during both respiratory illnesses and scheduled surveillance visits (P < 0.001, χ2) in older children. The prevalence of neutralizing antibodies to RV-A or RV-C types was low (5-27%) at the age of 2 years, but by the age of 16 years, RV-C seropositivity was more prevalent (78% vs. 18% for RV-A; P < 0.0001). In the pooled analysis, the RV-C to RV-A detection ratio during illnesses was significantly related to age (P < 0.0001), CDHR3 genotype (P < 0.05), and wheezing illnesses (P < 0.05). Furthermore, certain RV types (e.g., C2, C11, A78, and A12) were consistently more virulent and prevalent over time.Conclusions: Knowledge of prevalent RV types, antibody responses, and populations at risk based on age and genetics may guide the development of vaccines or other novel therapies against this important respiratory pathogen. [ABSTRACT FROM AUTHOR]

This article examines the development and peacetime activities of the Norwegian Coast Guard through the lens of sea control. It argues that the creation of economic and fisheries protection zones has dramatically shaped the extent to which a smaller naval power, like Norway, has had to increase its ability to monitor and control maritime space. Although the maritime means and ends vary widely between peacetime and wartime contexts, the fundamentally contested aspect of sea use can still be discerned in the influence of international maritime law on Norwegian seapower. [ABSTRACT FROM AUTHOR]

Adult spinal deformity is a complex pathology requiring careful consideration of patient-related parameters, comorbidities, overall clinical and radiographic alignment to determine individualized treatment. There has been an advent of interbody fusion techniques, advancements in fusion devices, and various approaches to insert spacers to achieve optimal sagittal and coronal balance. However, there is lack of clear evidence to support superiority of one technique versus others with minor differences in fusion outcomes across techniques and ability to correct deformity parameters. Ultimately, the decision is based on surgeon familiarity with techniques, fusion devices, and approaches. [ABSTRACT FROM AUTHOR]

The article discusses a study about the Ottoman area-denial operations. The study examines the extent to which Ottoman area-denial operations in the Dardanelles can provide a rough outline for Iranian actions in the Strait of Hormuz. It also explores the details of the Dardanelles campaign and analyzes the applicability of the campaign's conclusions to the modern-day Strait of Hormuz scenario.

The article considers communal becoming as teacher leaders within a course which utilizes both informative and transformative pedagogy. It states that the militant pedagogy inspired the public to be empowered citizens who craft powerful contexts that call forth ways of being and acting to incite futures that will not happen without collective action. Creating a learning community, informative learning, and transformative learning are discussed.

Macrophage-mediated programmed cell removal (PrCR) is a process essential for the clearance of unwanted (damaged, dysfunctional, aged, or harmful) cells. The detection and recognition of appropriate target cells by macrophages is a critical step for successful PrCR, but its molecular mechanisms have not been delineated. Here using the models of tissue turnover, cancer immunosurveillance, and hematopoietic stem cells, we show that unwanted cells such as aging neutrophils and living cancer cells are susceptible to “labeling” by secreted calreticulin (CRT) from macrophages, enabling their clearance through PrCR. Importantly, we identified asialoglycans on the target cells to which CRT binds to regulate PrCR, and the availability of such CRT-binding sites on cancer cells correlated with the prognosis of patients in various malignancies. Our study reveals a general mechanism of target cell recognition by macrophages, which is the key for the removal of unwanted cells by PrCR in physiological and pathophysiological processes. Macrophage-mediated programmed cell removal (PrCR) allows clearance of living cells. Here the authors show that, in mouse models, activated macrophages create an “eat me” signal via calreticulin secretion on neutrophils during peritonitis and on cancer cells, determining in both cases clearance by PrCR. [ABSTRACT FROM AUTHOR]

Recalcitrant pain after total knee replacement (TKR) is sometimes treated with intra-articular steroid injections (IASI), with few studies reporting on the risk of subsequent periprosthetic joint infection (PJI). This is a systematic review to evaluate the incidence and risk of PJI after IASI into a total knee replacement. We searched online databases using the keywords "total knee replacement," "total knee arthroplasty," "steroids" and "intra-articular injection." A total of 7386 articles (PubMed - 91, Embase - 70, Web of Science - 57, CINAHL - 8, and Google Scholar - 7160) were retrieved on the initial search. After applying exclusion criteria, four articles were included in this review for evaluation and statistical analysis. There were no level one or two studies. The incidence of infection after IASI at 12 months was 138/6499 or 2.1%, while the incidence of infection rate among controls at 12 months was 158/11256 or 1.4%. A chi-square test showed that the difference in infection rate was significant (p = 0.0002424). A caveat is that simple statistical test results are virtually guaranteed to be statistically significant with large sample size. IASI into a TKR is not a benign procedure and that may be associated with a significantly increased risk of subsequent periprosthetic joint infection. We, therefore, recommend against IASI into a TKR until better studies can be performed to determine their safety and efficacy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Cheppalli et al.)

The CD47/signal regulatory protein α (Cd47/SIRPα)interaction provides a macrophage immune checkpoint pathway that plays a critical role in cancer immune evasion across multiple cancers. Here, we report the engineering of a humanized anti-SIRPα monoclonal antibody (1H9) for antibody target cancer therapy. 1H9 has broad activity across a wide range of SIRPα variants. Binding of 1H9 to SIRPα blocks its interaction with CD47, thereby promoting macrophage-mediated phagocytosis of cancer cells. Preclinical studies in vitro and in vivo demonstrate that 1H9 synergizes with other therapeutic antibodies to promote phagocytosis of tumor cells and inhibit tumor growth in both syngeneic and xenograft tumor models, leading to survival benefit. Thus, 1H9 can potentially act as a universal agent to enhance therapeutic efficacy when used in combination with most tumor-targeting antibodies. We report a comparison of anti-SIRPα and anti-CD47 antibodies in CD47/SIRPα double-humanized mice and found that 1H9 exhibits a substantially reduced antigen sink effect due to the limited tissue distribution of SIRPα expression. Toxicokinetic studies in nonhuman primates show that 1H9 is well tolerated, with no treatment-related adverse effects noted. These data highlight the clinical potential of 1H9 as a pan-therapeutic with the desired properties when used in combination with tumor-targeting antibodies.