When Law Frees Us to Speak

A central aim of online abuse is to silence victims. That effort is as regrettable as it is successful. In the face of cyberharassment and sexualprivacy invasions, women and marginalized groups retreat from online engagement. These documented chilling effects, however, are not inevitable. Beyond its deterrent function, the law has an equally important expressive role. In this Article, we highlight law’s capacity to shape social norms and behavior through education. We focus on a neglected dimension of law’s expressive role: its capacity to empower victims to express their truths and engage with others. Our argument is theoretical and empirical. We present new empirical research showing cyberharassment law’s salutary effects on women’s online expression. We then consider the implications of those findings for victims of sexual-privacy invasions

When Law Frees Us to Speak

A central aim of online abuse is to silence victims. That effort is as regrettable as it is successful. In the face of cyberharassment and sexualprivacy invasions, women and marginalized groups retreat from online engagement. These documented chilling effects, however, are not inevitable. Beyond its deterrent function, the law has an equally important expressive role. In this Article, we highlight law’s capacity to shape social norms and behavior through education. We focus on a neglected dimension of law’s expressive role: its capacity to empower victims to express their truths and engage with others. Our argument is theoretical and empirical. We present new empirical research showing cyberharassment law’s salutary effects on women’s online expression. We then consider the implications of those findings for victims of sexual-privacy invasions

The Impact of Resistance Exercise on Muscle Mass in Glioblastoma in Survivors (RESIST): Protocol for a Randomized Controlled Trial

BackgroundGlioblastoma is the most common primary brain malignancy in adults, accounting for approximately 48% of all brain tumors. Standard treatment includes radiation and temozolomide chemotherapy. Glioblastomas are highly vascular and can cause vasogenic brain edema and mass effect, which can worsen the neurologic symptoms associated with the disease. The steroid dexamethasone (DEX) is the treatment of choice to reduce vasogenic edema and intracranial pressure associated with glioblastoma. However high-dose DEX or long-term use can result in muscle myopathy in 10%-60% of glioblastoma patients, significantly reducing functional fitness and quality of life (QOL). There is a wealth of evidence to support the use of exercise as an adjuvant therapy to improve functional ability as well as help manage treatment-related symptoms. Specifically, resistance training has been shown to increase muscle mass, strength, and functional fitness in aging adults and several cancer populations. Although studies are limited, research has shown that exercise is safe and feasible in glioblastoma populations. However, it is not clear whether resistance training can be successfully used in glioblastoma to prevent or mitigate steroid-induced muscle myopathy and associated loss of function. ObjectiveThe primary purpose of this study is to establish whether an individualized circuit-based program will reduce steroid-induced muscle myopathy, as indicated by maintained or improved functional fitness for patients on active treatment and receiving steroids. MethodsThis is a 2-armed, randomized controlled trial with repeated measures. We will recruit 38 adult (≥18 years) patients diagnosed with either primary or secondary glioblastoma who are scheduled to receive standard radiation and concurrent and adjuvant temozolomide chemotherapy postsurgical debulking and received any dose of DEX through the neurooncology clinic and the Nova Scotia Health Cancer Center. Patients will be randomly allocated to a standard of care waitlist control group or standard of care + circuit-based resistance training exercise group. The exercise group will receive a 12-week individualized, group and home-based exercise program. The control group will be advised to maintain an active lifestyle. The primary outcome, muscle myopathy (functional fitness), will be assessed using the Short Physical Performance Battery and hand grip strength. Secondary outcome measures will include body composition, cardiorespiratory fitness, physical activity, QOL, fatigue, and cognitive function. All measures will be assessed pre- and postintervention. Participant accrual, exercise adherence, and safety will be assessed throughout the study. ResultsThis study has been funded by the Canadian Cancer Society Atlantic Cancer Research Grant and the J.D. Irving Limited–Excellence in Cancer Research Fund (grant number 707182). The protocol was approved by the Nova Scotia Health and Acadia University’s Research Ethics Boards. Enrollment is anticipated to begin in March 2022. ConclusionsThis study will inform how individualized circuit-based resistance training may improve functional independence and overall QOL of glioblastoma patients. Trial RegistrationClinicalTrails.gov NCT05116137; https://www.clinicaltrials.gov/ct2/show/NCT05116137 International Registered Report Identifier (IRRID)DERR1-10.2196/3770

Individualized genetic makeup that controls natural killer cell function influences the efficacy of isatuximab immunotherapy in patients with multiple myeloma.

Phase IIb clinical trial with isatuximab (Isa)-lenalidomide (Len)-dexamethasone (Dex) showed an improved progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma (RRMM), but the efficacy varied by patient. Antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) cells plays a crucial role in arbitrating antitumor activities of therapeutic-antibodies. We tested if patient-specific genetic makeup known to set NK cell functional threshold influence response to Isa-Len-Dex therapy. We characterized 57 patients with RRMM receiving Isa-Len-Dex for polymorphisms of killer-cell immunoglobulin-like receptors (KIR), human leukocyte antigen (HLA) class I, and FCGR3A loci. In vitro ADCC assay, coincubating primary NK cells expressing specific KIR repertoire with multiple myeloma cell lines (MM cells) expressing selected HLA class I ligands, was used to confirm the identified genetic correlatives of clinical response. Patients with KIR3DL2+ and its cognate-ligand HLA-A3/11+ had superior PFS than patients missing this combination (HR=0.43; p=0.02), while patients carrying KIR2DL1+ and HLA-C2C2+ compared with to patients missing this pair showed short PFS (HR=3.54; p=0.05). Patients with KIR3DL2+ and HLA-A3/11+ plus high-affinity FCGR3A-158V allele showed the most prolonged PFS (HR=0.35; p=0.007). Consistent with these clinical data, mechanistic experiments demonstrated that NK cells expressing KIR3DL2 trigger greater ADCC when MM cells express HLA-A3/11. Inversely, NK cells expressing KIR2DL1 do not kill if MM cells express the HLA-C2C2 ligand. NK cells expressing high-affinity FCGR3A-158VV-induced greater ADCC compared with those with low-affinity FCGR3A-158FF. Our results suggest that KIR3DL2+ and HLA-A3/11+ with FCGR3A-158V markers lead to enhanced Isa-dependent NK-mediated cytolysis against MM cells and results in improved PFS in patients with RRMM treated by Isa-Len-Dex. Moreover, the presence of KIR2DL1+ and HLA-C2C2+ identifies patients who may have a lower response to Isa-Len-Dex therapy linked to a reduced NK-mediated ADCC. These biomarkers could potentially identify, via precision medicine, patients more likely to respond to Isa-Len-Dex immunotherapy. NCT01749969