Bordering migration/migrating borders

From the Great Wall of China to the Berlin Wall, border walls have long served as symbols of visible, fortified manifestations of sovereign control. Increasingly, however, prosperous countries utilize sophisticated legal tools to restrict mobility by detaching the border and its migration control functions from a fixed territorial marker, creating a new framework: the shifting border. This shifting border, unlike a reinforced physical barrier, is not fixed in time and place. It relies on law’s admission gates rather than a specific frontier location. The remarkable development of recent years is that the border itself has become a moving barrier, an unmoored legal construct. These dramatic transformations unsettle ideas about waning sovereignty just as they illustrate the limits of the push toward border-fortification. By charting the logic of a new cartography of borders and membership boundaries, Professor Shachar shows both the tremendous creativity and risk attached to these new legal innovations and the public powers they invigorate and propagate. This Article further demonstrates that debates about migration and globalization can no longer revolve around the dichotomy between open versus closed borders. As an alternative to these established theoretical poles and as part of a broader attempt to overcome policy deadlocks at the domestic and international level, Professor Shachar proposes a new approach to human mobility and access to membership in a world marred by unequal opportunities for protection and migration

Shifting borders: invisible, but very real

Today’s borders are no longer necessarily made of bricks and barbed wire. They are increasingly becoming moving barriers that rely on cutting-edge technologies and complex regulations to impose travel restrictions on citizens. The COVID-19 pandemic has further accentuated this phenomenon

Safety and Tolerability of PD‐1/PD‐L1 Inhibitors Compared with Chemotherapy in Patients with Advanced Cancer: A Meta‐Analysis

BACKGROUND: Compared with chemotherapy, significant improvement in survival outcomes with the programmed death receptor-1 (PD-1) inhibitors nivolumab and pembrolizumab and the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab has been shown in several types of advanced solid tumors. We conducted a systematic review and meta-analysis to compare safety and tolerability between PD-1/PD-L1 inhibitors and chemotherapy. METHODS: PubMed and American Society of Clinical Oncology (ASCO) databases were searched 1966 to September 2016. Eligible studies included randomized controlled trials (RCTs) comparing single-agent U.S. Food and Drug Administration-approved PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, or atezolizumab) with chemotherapy in cancer patients reporting any all-grade (1-4) or high-grade (3-4) adverse events (AEs), all- or high-grade treatment-related symptoms, hematologic toxicities and immune-related AEs, treatment discontinuation due to toxicities, or treatment-related deaths. The summary incidence, relative risk, and 95% confidence intervals were calculated. RESULTS: A total of 3,450 patients from 7 RCTs were included in the meta-analysis: 4 nivolumab, 2 pembrolizumab, and 1 atezolizumab trials. The underlying malignancies included were non-small cell lung cancer (4 trials) and melanoma (3 trials). Compared with chemotherapy, the PD-1/PD-L1 inhibitors had a significantly lower risk of all- and high-grade fatigue, sensory neuropathy, diarrhea and hematologic toxicities, all-grade anorexia, nausea, and constipation, any all- and high-grade AEs, and treatment discontinuation. There was an increased risk of all-grade rash, pruritus, colitis, aminotransferase elevations, hypothyroidism, and hyperthyroidism, and all- and high-grade pneumonitis with PD1/PD-L1 inhibitors. CONCLUSION: PD-1/PD-L1 inhibitors are overall better tolerated than chemotherapy. Our results provide further evidence supporting the favorable risk/benefit ratio for PD-1/PD-L1 inhibitors. The Oncologist 2017;22:470-479 IMPLICATIONS FOR PRACTICE: We conducted a systematic review and meta-analysis to compare summary toxicity endpoints and clinically relevant adverse events between programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and chemotherapy. PD1/PD-L1 inhibitors were associated with a lower risk of treatment-related symptoms (fatigue, anorexia, nausea, diarrhea, constipation, and sensory neuropathy) but a higher risk of immune-related adverse events (AEs). Summary toxicity endpoints favor PD1/PD-L1 inhibitors (any all- and high-grade AEs and treatment discontinuation). PD1/PD-L1 inhibitors are overall better tolerated than chemotherapy. In addition to efficacy data from trials, our findings provide useful information for clinicians for well-balanced discussions with their patients on the risks and benefits of treatment options for advanced cancer

Homeostasis in C. elegans sleep is characterized by two behaviorally and genetically distinct mechanisms

Biological homeostasis invokes modulatory responses aimed at stabilizing internal conditions. Using tunable photo- and mechano-stimulation, we identified two distinct categories of homeostatic responses during the sleep-like state of Caenorhabditis elegans (lethargus). In the presence of weak or no stimuli, extended motion caused a subsequent extension of quiescence. The neuropeptide Y receptor homolog, NPR-1, and an inhibitory neuropeptide known to activate it, FLP-18, were required for this process. In the presence of strong stimuli, the correlations between motion and quiescence were disrupted for several minutes but homeostasis manifested as an overall elevation of the time spent in quiescence. This response to strong stimuli required the function of the DAF-16/FOXO transcription factor in neurons, but not that of NPR-1. Conversely, response to weak stimuli did not require the function of DAF-16/FOXO. These findings suggest that routine homeostatic stabilization of sleep may be distinct from homeostatic compensation following a strong disturbance. DOI: http://dx.doi.org/10.7554/eLife.04380.00

Body Composition as a Predictor of Toxicity in Patients Receiving Anthracycline and Taxane–Based Chemotherapy for Early-Stage Breast Cancer

Poor body composition metrics (BCM) are associated with inferior cancer outcomes; however, in early breast cancer (EBC) there is a paucity of evidence regarding BCM’s impact on toxicities. This study investigates associations between BCM and treatment-related toxicity in EBC patients receiving anthracyclines-taxane based chemotherapy

Skeletal Muscle Measures as Predictors of Toxicity, Hospitalization, and Survival in Patients with Metastatic Breast Cancer Receiving Taxane-Based Chemotherapy

Severe skeletal muscle (SM) loss (sarcopenia), is associated with poor cancer outcomes including reduced survival and increased toxicity. This study investigates SM measures in metastatic breast cancer (MBC) patients receiving first line taxane-based chemotherapy and evaluates associations with treatment toxicity and other outcomes

Skeletal muscle measures and physical function in older adults with cancer: sarcopenia or myopenia?

BACKGROUND: Skeletal muscle loss, commonly known as sarcopenia, is highly prevalent in older adults and linked with adverse outcomes in cancer, yet the definition and role of sarcopenia remains uncertain. The aim of this study was to examine the association of Computerized Tomography (CT) assessed skeletal muscle measures with physical function in older adults with cancer. RESULTS: CTs for 185 patients were available. Median age 73 (IQR 68-76) and 56.5% female. After controlling for sex and BMI, we found no evidence that SMI was associated with physical function impairments. Both SMD and SMG were associated physical function impairments and higher values were associated with decreased limitations in instrumental activities of daily living (RR 0.84 [CI 0.73-0.96] and 0.94 [CI 0.89-0.99], respectively), climbing stairs (RR 0.84 [CI 0.76-0.94] and 0.91 [CI 0.87-0.96]), walking 1 block (RR 0.77 [CI 0.67-0.90] and 0.91 [CI 0.85-0.97]), and prolonged Timed Up and Go (RR 0.83 [CI 0.75-0.92] and 0.92 [CI 0.88-0.96]). MATERIALS AND METHODS: Using the Carolina Senior Registry, we identified patients with CT imaging performed within 60 days +/- of baseline geriatric assessment (GA). Skeletal muscle area and density (SMD) were analyzed from L3 lumbar segments. Muscle area and height (m2) were used to calculate skeletal muscle index (SMI). Skeletal Muscle Gauge (SMG) was created by multiplying SMI x SMD. CONCLUSIONS: Skeletal muscle mass as assessed from CT imaging was not associated with physical function impairments. Skeletal muscle radiodensity was more associated with physical function and may aid in identifying older adults at risk for functional impairments