The Future of Legal Scholarship and Scholarly Communication: Publication in the Age of Cyberspace

In Part I of this paper, I will review the essentials of Hibbitts\u27s discussion, and his argument that electronic self-publication of legal scholarship soon willand shouldreplace the edited, printed law review as we know it today. In Part II, I apply sociological analysis to explore some special features of the audience for and functions of legal scholarship. I will build upon this discussion in Part III, which explains why legal scholarship is a poor candidate for electronic self-publication, and why self-publication is a poor use of the Internet\u27s potential for scholarly communication. In the concluding Part IV, I outline some counter-proposals for improving legal scholarship and scholarly communication in light of new dissemination technologies

Do health policy advisors know what the public wants? An empirical comparison of how health policy advisors assess public preferences regarding smoke-free air, and what the public actually prefers

Background: Health policy-making, a complex, multi-factorial process, requires balancing conflicting values. A salient issue is public support for policies; however, one reason for limited impact of public opinion may be misperceptions of policy makers regarding public opinion. For example, empirical research is scarce on perceptions of policy makers regarding public opinion on smoke-free public spaces. Methods: Public desire for smoke-free air was compared with health policy advisor (HPA) perception of these desires. Two representative studies were conducted: one with the public (N = 505), and the other with a representative sample of members of Israel’s health-targeting initiative, Healthy Israel 2020 (N = 34), in December 2010. Corresponding questions regarding desire for smoke-free areas were asked. Possible smoke-free areas included: 100% smoke-free bars and pubs; entrances to health facilities; railway platforms; cars with children; college campuses; outdoor areas (e.g., pools and beaches); and common areas of multi-dweller apartment buildings. A 1–7 Likert scale was used for each measure, and responses were averaged into a single primary outcome, DESIRE. Our primary endpoint was the comparison between public preferences and HPA assessment of those preferences. In a secondary analysis, we compared personal preferences of the public with personal preferences of the HPAs for smoke-free air. Results: HPAs underestimated public desire for smoke-free air (Public: Mean: 5.06, 95% CI:[4.94, 5.17]; HPA: Mean: 4.06, 95% CI:[3.61, 4.52]: p < .0001). Differences at the p = .05 level were found between HPA assessment and public preference for the following areas: 100% smoke-free bars and pubs; entrances to healthcare facilities; train platforms; cars carrying children; and common areas of multi-dweller apartment buildings. In our secondary comparison, HPAs more strongly preferred smoke-free areas than did the public (p < .0001). Conclusions: Health policy advisors underestimate public desire for smoke-free air. Better grasp of public opinion by policy makers may lead to stronger legislation. Monitoring policy-maker assessment of public opinion may shed light on incongruities between policy making and public opinion. Further, awareness of policy-maker misperceptions may encourage policy-makers to demand more accurate information before making policy

Prognostic impact of low muscle mass and low muscle density in patients with diffuse large B-cell lymphoma

Low muscle mass (LMM) and low muscle density (LMD) are increasingly recognized as prognostic factors for survival in different malignancies. This study determined the association of LMM and LMD with survival in DLBCL (diffuse large B-cell lymphoma) patients. CT-based measurement of muscle was performed in 164 DLBCL patients prior to chemo-immunotherapy. Z-scores adjusted for gender, age, and body mass index were derived from a healthy reference population. LMM or LMD were defined as a Z-score below −1 and were related to OS and PFS. The co-existence of both LMM and LMD was observed in 13% of the DLBCL patients and was significantly associated with shorter OS and PFS. Also, these patients more often did not complete the planned treatment. The combination of LMM and LMD is an independent prognosti

First-line palliative HER2-targeted therapy in HER2-positive metastatic breast cancer is less effective after previous adjuvant trastuzumab-based therapy

Background. Survival of patients with human epidermal growth receptor 2 (HER2)-positive metastatic breast cancer (MBC) has improved dramatically since trastuzumab has become available, although the disease eventually progresses in most patients. This study investigates the outcome (overall survival [OS] and time to next treatment [TNT]) in MBC patients pretreated with trastuzumab in the adjuvant setting (TP-group) compared with trastuzumab-näive patients (TN-group) in order to investigate the possibility of trastuzumab resistance. Patients and Methods. Patients treated with first-line HER2-targeted- containing chemotherapy were eligible for the study. A power analysis was performed to estimate the minimum size of the TP-group. OS and TNT were estimated using Kaplan-Meier curves andmultivariable Cox proportional hazards models. Results. Between January 1, 2000, and June 1, 2014, 469 patients were included, of whom 82 were in the TP-group and 387 were in the TN-group. Median OS and TNT were significantly worse in the TP-group compared with the TN-group (17 vs. 30 months, adjusted hazard ratio [HR] 1.84 [1.15-2.96], p5.01 and 7 vs. 13 months, adjusted HR 1.65 [1.06-2.58], p5.03) after adjustment for age, year of diagnosis, diseasefree interval, hormone receptor status, metastatic site, and cytotoxic regimens. Conclusion. First-line trastuzumab-containing treatment regimens are less effective in patients with failure of adjuvant trastuzumab compared with trastuzumab-näive patients and might be due to trastuzumab resistance. The impact of trastuzumab resistance on the response on dual HER2 blockade with trastuzumab and pertuzumab and how resistance mechanisms can be used in the optimization of HER2-targeted treatment lines need further investigation.</p

The effect of trastuzumab on cardiac function in patients with HER2-positive metastatic breast cancer and reduced baseline left ventricular ejection fraction

We investigated the effect of trastuzumab on cardiac function in a real‐world historic cohort of patients with HER2‐positive metastatic breast cancer (MBC) with reduced baseline left ventricular ejection fraction (LVEF). Thirty‐seven patients with HER2‐positive MBC and baseline LVEF of 40% to 49% were included. Median LVEF was 46% (interquartile range [IQR] 44%‐48%) and median follow‐up was 18 months (IQR 9‐34 months). During this period, the LVEF did not worsen in 24/37 (65%) patients, while 13/37 (35%) patients developed severe cardiotoxicity defined as LVEF 5%‐points below baseline) in 3/13 (23%) patients and irreversible (defined as absolute LVEF increase 5%‐points below baseline) in 3/13 (23%) patients. Likelihood of reversibility was numerically higher in patients who received cardio‐protective medications (CPM), including ACE‐inhibitors, beta‐blockers and angiotensine‐2 inhibitors, compared to those who did not receive any CPM (71% vs 13%, P = .091). Sixty‐five percent of patients who received trastuzumab for HER2‐positive MBC did not develop severe cardiotoxicity during a median follow‐up of 18 months, despite having a compromised baseline LVEF. If severe cardiotoxicity occurred, it was at least partly reversible in more than two‐thirds of the cases. Risks and benefits of trastuzumab use should be balanced carefully in this vulnerable population

Prevalence of hospital PCR-confirmed COVID-19 cases in patients with chronic inflammatory and autoimmune rheumatic diseases

[Abstract] Background: The susceptibility of patients with rheumatic diseases and the risks or benefits of immunosuppressive therapies for COVID-19 are unknown. Methods: We performed a retrospective study with patients under follow-up in rheumatology departments from seven hospitals in Spain. We matched updated databases of rheumatology patients with severe acute respiratory syndrome coronavirus 2-positive PCR tests performed in the hospital to the same reference populations. Rates of PCR+ confirmed COVID-19 were compared among groups. Results: Patients with chronic inflammatory diseases had 1.32-fold higher prevalence of hospital PCR+ COVID-19 than the reference population (0.76% vs 0.58%). Patients with systemic autoimmune or immune-mediated disease (AI/IMID) showed a significant increase, whereas patients with inflammatory arthritis (IA) or systemic lupus erythematosus did not. COVID-19 cases in some but not all diagnostic groups had older ages than cases in the reference population. Patients with IA on targeted-synthetic or biological disease-modifying antirheumatic drugs (DMARDs), but not those on conventional-synthetic DMARDs, had a greater prevalence despite a similar age distribution. Conclusion: Patients with AI/IMID show a variable risk of hospital-diagnosed COVID-19. Interplay of ageing, therapies and disease-specific factors seem to contribute. These data provide a basis to improve preventive recommendations to rheumatic patients and to analyse the specific factors involved in COVID-19 susceptibility.Instituto de Salud Carlos III; RD16/0012 RETICS Progra

OPM-MEG in multiple sclerosis:proof of principle, and the effect of naturalistic posture

Multiple Sclerosis (MS) is a common neurological disorder in which myelin damage affects neuronal signalling. Magnetoencephalography (MEG – the measurement of magnetic fields generated by neuronal currents) offers metrics of brain function that relate directly to electrophysiological signalling, making it a valuable tool for exploring how abnormal function relates to MS symptoms. However, conventional MEG requires participants to be seated or supine with limited head and body motion. This makes it hard to measure brain function whilst simultaneously asking patients to carry out tasks they find challenging – many of which relate to movement. Here, we used a newly developed OPM-MEG system, with a wearable helmet and a lightweight backpack-mounted control unit, to measure MEG signals in people with MS (pwMS), both at rest and during a visuo-motor task. Uniquely, our system enabled data collection in participants who were seated and standing. We found that established markers of MS – including delayed beta-band responses to finger movement and diminished gamma-band responses to visual stimulation – were measurable using OPM-MEG. Further, we showed that standing (compared to sitting) decreased beta-band connectivity (in patients and controls, but the effect was only significant in controls) and decreased oscillatory power (in patients but not controls). In summary, our paper confirms that OPM-MEG is a useful means to investigate MS; it also demonstrates the importance of investigating how changes in posture relate to oscillations and connectivity, and lays the groundwork for broader studies of movement

Wearable magnetoencephalography in a lightly shielded environment

Wearable magnetoencephalography based on optically pumped magnetometers (OPM-MEG) offers non-invasive and high-fidelity measurement of human brain electrophysiology. The flexibility of OPM-MEG also means it can be deployed in participants of all ages and permits scanning during movement. However, the magnetic fields generated by neuronal currents – which form the basis of the OPM-MEG signal – are much smaller than environmental fields, and this means measurements are highly sensitive to interference. Further, OPMs have a low dynamic range, and should be operated in near-zero background field. Scanners must therefore be housed in specialised magnetically shielded rooms (MSRs), formed from multiple layers of shielding material. The MSR is a critical component, and current OPM-optimised shields are large (>3 m in height), heavy (>10,000 kg) and expensive (with up to 5 layers of material). This restricts the uptake of OPM-MEG technology. Here, we show that the application of the Maxwell filtering techniques signal space separation (SSS) and its spatiotemporal extension (tSSS) to OPM-MEG data can isolate small signals of interest measured in the presence of large interference. We compare phantom recordings and MEG data from a participant performing a motor task in a state-of-the-art 5-layer MSR, to similar data collected in a lightly shielded room: application of tSSS to data recorded in the lightly shielded room allowed accurate localisation of a dipole source in the phantom and neuronal sources in the brain. Our results point to future deployment of OPM-MEG in lighter, cheaper and easier-to-site MSRs which could catalyse widespread adoption of the technology

The influence of body composition on the systemic exposure of paclitaxel in esophageal cancer patients

Changes in body composition are associated with chemotherapy-related toxicities and effectiveness of treatment. It is hypothesized that the pharmacokinetics (PK) of chemotherapeutics may depend on body composition. The effects of body composition on the variability of paclitaxel PK were studied in patients with esophageal cancer. Skeletal muscle index (SMI), visceral adipose tissue (VAT), and skeletal muscle density (SMD) were measured at the third lumbar vertebra on computed tomography (CT) scans performed before treatment. Paclitaxel PK data were collected from a prospective study performed between May 2004 and January 2014. Non-linear mixed-effects modeling was used to fit paclitaxel PK profiles and evaluate the covariates body surface area (BSA), SMI, VAT, and SMD using a significance threshold of p < 0.001. Paclitaxel was administered to 184 patients in a dose range of 50 to 175 mg/m2 . Median BSA was 1.98 m2 (range of 1.4 to 2.8 m2 ). SMI, VAT, and SMD were not superior to BSA in predicting paclitaxel PK. The additive value of SMI, VAT, and SMD to BSA was also negligible. We did not find evidence that paclitaxel dosing could be further optimized by correcting for SMI, VAT, or SMD

Cardiotoxicity during long-term trastuzumab use in patients with HER2-positive metastatic breast cancer: who needs cardiac monitoring?

Purpose: Patients with HER2-positive metastatic breast cancer (MBC) usually receive many years of trastuzumab treatment. It is unknown whether these patients require continuous left ventricular ejection fraction (LVEF) monitoring. We studied a real-world cohort to identify risk factors for cardiotoxicity to select patients in whom LVEF monitoring could be omitted. Methods: We included patients with HER2-positive MBC who received > 1 cycle of trastuzumab-based therapy in eight Dutch hospitals between 2000 and 2014. Cardiotoxicity was defined as LVEF 10%-points and was categorized into non-severe cardiotoxicity (LVEF 40–50%) and severe cardiotoxicity (LVEF 60% and no cardiotoxicity during prior neoadjuvant/adjuvant treatment, the cumulative incidence of severe cardiotoxicity was 3.1% after 4 years of trastuzumab. Despite continuing trastuzumab, LVEF decline was reversible in 56% of patients with non-severe cardiotoxicity and in 33% with severe cardiotoxicity. Conclusions: Serial cardiac monitoring can be safely omitted in non-smoking patients with baseline LVEF > 60% and without cardiotoxicity during prior neoadjuvant/adjuvant treatment