Efficacy and safety assessment of prolonged maintenance with subcutaneous rituximab in patients with relapsed or refractory indolent non-Hodgkin lymphoma: results of the phase III MabCute study

Rituximab plus chemotherapy induction followed by rituximab maintenance for up to 2 years confers a long-term benefit in terms of progression-free survival in patients with indolent non-Hodgkin lymphoma. It is not known whether further prolonged maintenance with rituximab provides additional benefit. The phase III MabCute study enrolled 692 patients with relapsed or refractory indolent non-Hodgkin lymphoma. Patients who responded to induction with rituximab plus chemotherapy and were still responding after up to 2 years’ initial maintenance with subcutaneous rituximab were randomized to extended maintenance with subcutaneous rituximab (n=138) or observation only (n=138). The primary endpoint of investigator-assessed progression-free survival in the randomized population was un-addressed by the end of study because of an insufficient number of events (129 events were needed for 80% power at 5% significance if approximately 330 patients were randomized). In total, there were 46 progression-free survival events, 19 and 27 in the rituximab and observation arms, respectively (P=0.410 by stratified log-rank test; hazard ratio 0.76 [95% confidence interval: 0.37– 1.53]). The median progression-free survival was not reached in either randomized arm. There were no new safety signals; however, adverse events were seen slightly more frequently with rituximab than with observation during extended maintenance. Maintenance for up to 2 years with rituximab after response to initial induction therefore remains the standard of care in patients with relapsed or refractory indolent non- Hodgkin lymphoma. (Clinicaltrials.gov identifier: NCT01461928).</jats:p

Comprehensive Evaluation of Corticospinal Tract Metabolites in Amyotrophic Lateral Sclerosis Using Whole-Brain 1H MR Spectroscopy

Changes in the distribution of the proton magnetic resonance spectroscopy (MRS) observed metabolites N-acetyl aspartate (NAA), total-choline (Cho), and total-creatine (Cre) in the entire intracranial corticospinal tract (CST) including the primary motor cortex were evaluated in patients with amyotrophic lateral sclerosis (ALS). The study included 38 sporadic definite-ALS subjects and 70 age-matched control subjects. All received whole-brain MR imaging and spectroscopic imaging scans at 3T and clinical neurological assessments including percentage maximum forced vital capacity (FVC) and upper motor neuron (UMN) function. Differences in each individual metabolite and its ratio distributions were evaluated in the entire intracranial CST and in five segments along the length of the CST (at the levels of precentral gyrus (PCG), centrum semiovale (CS), corona radiata (CR), posterior limb of internal capsule (PLIC) and cerebral peduncle (CP)). Major findings included significantly decreased NAA and increased Cho and Cho/NAA in the entire intracranial CST, with the largest differences for Cho/NAA in all the groups. Significant correlations between Cho/NAA in the entire intracranial CST and the right finger tap rate were noted. Of the ten bilateral CST segments, significantly decreased NAA in 4 segments, increased Cho in 5 segments and increased Cho/NAA in all the segments were found. Significant left versus right CST asymmetries were found only in ALS for Cho/NAA in the CS. Among the significant correlations found between Cho/NAA and the clinical assessments included the left-PCG versus FVC and right finger tap rate, left -CR versus FVC and right finger tap rate, and left PLIC versus FVC and right foot tap rate. These results demonstrate that a significant and bilaterally asymmetric alteration of metabolites occurs along the length of the entire intracranial CST in ALS, and the MRS metrics in the segments correlate with measures of disease severity and UMN function

Guilds in the transition to modernity: the cases of Germany, United Kingdom, and the Netherlands

One important aspect of the transition to modernity is the survival of elements of the Old Regime beyond the French Revolution. It has been claimed that this can explain why in the late 19th and early 20th centuries some Western countries adopted national corporatist structures while others transformed into liberal market economies. One of those elements is the persistence or absence of guild traditions. This is usually analyzed in a national context. This paper aims to contribute to the debate by investigating the development of separate trades in Germany, the United Kingdom and the Netherlands throughout the 19th century. We distinguish six scenarios of what might have happened to crafts and investigate how the prevalence of each of these scenarios in the three countries impacted on the emerging national political economies. By focusing on trades, rather than on the national political economy, our analysis demonstrates that in each country the formation of national political economies and citizenship rights was not the result of a national pattern of guild survival. Rather, the pattern that emerged by the end of the 19th century was determined by the balance between old and new industries, and between national and regional or local government

Investigating large-scale brain dynamics using field potential recordings: Analysis and interpretation

New technologies to record electrical activity from the brain on a massive scale offer tremendous opportunities for discovery. Electrical measurements of large-scale brain dynamics, termed field potentials, are especially important to understanding and treating the human brain. Here, our goal is to provide best practices on how field potential recordings (EEG, MEG, ECoG and LFP) can be analyzed to identify large-scale brain dynamics, and to highlight critical issues and limitations of interpretation in current work. We focus our discussion of analyses around the broad themes of activation, correlation, communication and coding. We provide best-practice recommendations for the analyses and interpretations using a forward model and an inverse model. The forward model describes how field potentials are generated by the activity of populations of neurons. The inverse model describes how to infer the activity of populations of neurons from field potential recordings. A recurring theme is the challenge of understanding how field potentials reflect neuronal population activity given the complexity of the underlying brain systems

Adipose depots differ in cellularity, adipokines produced, gene expression, and cell systems

The race to manage the health concerns related to excess fat deposition has spawned a proliferation of clinical and basic research efforts to understand variables including dietary uptake, metabolism, and lipid deposition by adipocytes. A full appreciation of these variables must also include a depot-specific understanding of content and location in order to elucidate mechanisms governing cellular development and regulation of fat deposition. Because adipose tissue depots contain various cell types, differences in the cellularity among and within adipose depots are presently being documented to ascertain functional differences. This has led to the possibility of there being, within any one adipose depot, cellular distinctions that essentially result in adipose depots within depots. The papers comprising this issue will underscore numerous differences in cellularity (development, histogenesis, growth, metabolic function, regulation) of different adipose depots. Such information is useful in deciphering adipose depot involvement both in normal physiology and in pathology. Obesity, diabetes, metabolic syndrome, carcass composition of meat animals, performance of elite athletes, physiology/pathophysiology of aging, and numerous other diseases might be altered with a greater understanding of adipose depots and the cells that comprise them—including stem cells—during initial development and subsequent periods of normal/abnormal growth into senescence. Once thought to be dormant and innocuous, the adipocyte is emerging as a dynamic and influential cell and research will continue to identify complex physiologic regulation of processes involved in adipose depot physiology

Prevalence of renal stones in an Italian urban population: a general practice-based study

Kidney stones represent a common condition characterized by significant morbidity and economic costs. The epidemiology of kidney stones is not completely understood and may vary substantially based on geographic, socioeconomic and clinical factors; the present study aims at defining the prevalence and diagnostic patterns of kidney stones in a cohort representative of the general population in Florence, Italy. A sample of 1,543 adult subjects, all Caucasians, was randomly selected from a population of over 25,000 subjects followed by 22 general practitioners (GPs). Subjects were administered a questionnaire requesting the patient's age and sex, any history of kidney stones and/or colics and the prescription of kidney ultrasound (US) examination. GPs data-bases were also interrogated. Crude and adjusted prevalence proportions and ratios (PRs) with corresponding 95\ua0% confidence intervals (CIs) were computed. Furthermore, the association between the practice pattern of each physician with respect to US prescription and the prevalence of kidney stones was investigated. The overall prevalence of kidney stones was 7.5\ua0% (95\ua0% confidence interval 6.2, 8.9\ua0%), increasing with age until 55-60\ua0years and then decreasing. About 50\ua0% reported recurrent disease. There were no significant differences in prevalence among males and females. GPs who tended to prescribe more US examinations were more likely to have more patients with kidney stones (adjusted PR 1.80, 95\ua0% CI 1.11, 2.94; p\ua0=\ua00.020). The present study confirms both the high prevalence and the regional variability of kidney stones. Practice patterns may be involved in such variability