PURPOSE To determine the frequency, characteristics, and reversibility of peripheral neuropathy from bortezomib treatment of advanced multiple myeloma. PATIENTS AND METHODS Peripheral neuropathy was assessed in two phase II studies in 256 patients with relapsed and/or refractory myeloma treated with bortezomib 1.0 or 1.3 mg/m2 intravenous bolus on days 1, 4, 8, and 11, every 21 days, for up to eight cycles. Peripheral neuropathy was evaluated at baseline, during the study, and after the study by patient-reported symptoms using the Functional Assessment of Cancer Therapy Scale/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire and neurologic examination. During the study, peripheral neuropathy was also evaluated by investigator assessment. A subset of patients underwent nerve conduction studies (n = 13). RESULTS Before treatment, 194 (81%) of 239 patients had peripheral neuropathy by FACT/GOG-Ntx questionnaire, and 203 (83%) of 244 patients had peripheral neuropathy by neurologic examination. Treatment-emergent neuropathy was reported in 35% of patients, including 37% (84 of 228 patients) receiving bortezomib 1.3 mg/m2 and 21% (six of 28 patients) receiving bortezomib 1.0 mg/m2. Grade 1 or 2, 3, and 4 neuropathy occurred in 22%, 13%, and 0.4% of patients, respectively. The incidence of grade > or = 3 neuropathy was higher among patients with baseline neuropathy by FACT/GOG-Ntx questionnaire compared with patients without baseline neuropathy (14% v 4%, respectively). In all 256 patients, neuropathy led to dose reduction in 12% and discontinuation in 5%. Of 35 patients with neuropathy > or = grade 3 and/or requiring discontinuation, resolution to baseline or improvement occurred in 71%. CONCLUSION Bortezomib-associated peripheral neuropathy seemed reversible in the majority of patients after dose reduction or discontinuation. Although severe neuropathy was more frequent in the presence of baseline neuropathy, the overall occurrence was independent of baseline neuropathy or type of prior therapy.

Significance Although scientists have identified surprising cognitive flexibility in animals and potentially unique features of human psychology, we know less about the selective forces that favor cognitive evolution, or the proximate biological mechanisms underlying this process. We tested 36 species in two problem-solving tasks measuring self-control and evaluated the leading hypotheses regarding how and why cognition evolves. Across species, differences in absolute (not relative) brain volume best predicted performance on these tasks. Within primates, dietary breadth also predicted cognitive performance, whereas social group size did not. These results suggest that increases in absolute brain size provided the biological foundation for evolutionary increases in self-control, and implicate species differences in feeding ecology as a potential selective pressure favoring these skills. Cognition presents evolutionary research with one of its greatest challenges. Cognitive evolution has been explained at the proximate level by shifts in absolute and relative brain volume and at the ultimate level by differences in social and dietary complexity. However, no study has integrated the experimental and phylogenetic approach at the scale required to rigorously test these explanations. Instead, previous research has largely relied on various measures of brain size as proxies for cognitive abilities. We experimentally evaluated these major evolutionary explanations by quantitatively comparing the cognitive performance of 567 individuals representing 36 species on two problem-solving tasks measuring self-control. Phylogenetic analysis revealed that absolute brain volume best predicted performance across species and accounted for considerably more variance than brain volume controlling for body mass. This result corroborates recent advances in evolutionary neurobiology and illustrates the cognitive consequences of cortical reorganization through increases in brain volume. Within primates, dietary breadth but not social group size was a strong predictor of species differences in self-control. Our results implicate robust evolutionary relationships between dietary breadth, absolute brain volume, and self-control. These findings provide a significant first step toward quantifying the primate cognitive phenome and explaining the process of cognitive evolution.

Aim To determine differences in physical activity level and functional fitness between young elderly (60–69 years) and old elderly (70–80 years) people with the hypothesis that an age-related decline would be found. Methods A total of 1288 participants’ level of physical activity was evaluated using the International Physical Activity Questionnaire: 594 were male (mean ± standard deviation: body height 175.62 ± 9.78 cm; body weight 82.26 ± 31.33 kg) and 694 female (mean ± standard deviation: body height 165.17 ± 23.12 cm; body weight 69.74 ± 12.44 kg). Functional fitness was also estimated using the Senior Fitness Test: back scratch, chair sit and reach, 8-foot up and go, chair stand up for 30 seconds, arm curl, and 2-minute step test. Results Significant differences (P < 0.05) were found for all Senior Fitness tests between young elderly (60–69 years) and old elderly (70–80) men. Similar results were found for the women, except no significant differences were found for the chair sit and reach and the 2-minute step test. From the viewpoint of energy consumption estimated by the International Physical Activity Questionnaire, moderate physical activity is dominant. In addition, with aging, among men and women older than 60 years, the value of the Metabolic Equivalent of Task in total physical activity significantly reduces (P < 0.05). Conclusions This study found that the reduction in physical activity level and functional fitness was equal for both men and women and was due to the aging process. These differences between young and old elderly people were due to the reduction of muscle strength in both upper and lower limbs and changes in body-fat percentage, flexibility, agility, and endurance.

In this paper, a new multi-criteria problem solving method—the Full Consistency Method (FUCOM)—is proposed. The model implies the definition of two groups of constraints that need to satisfy the optimal values of weight coefficients. The first group of constraints is the condition that the relations of the weight coefficients of criteria should be equal to the comparative priorities of the criteria. The second group of constraints is defined on the basis of the conditions of mathematical transitivity. After defining the constraints and solving the model, in addition to optimal weight values, a deviation from full consistency (DFC) is obtained. The degree of DFC is the deviation value of the obtained weight coefficients from the estimated comparative priorities of the criteria. In addition, DFC is also the reliability confirmation of the obtained weights of criteria. In order to illustrate the proposed model and evaluate its performance, FUCOM was tested on several numerical examples from the literature. The model validation was performed by comparing it with the other subjective models (the Best Worst Method (BWM) and Analytic Hierarchy Process (AHP)), based on the pairwise comparisons of the criteria and the validation of the results by using DFC. The results show that FUCOM provides better results than the BWM and AHP methods, when the relation between consistency and the required number of the comparisons of the criteria are taken into consideration. The main advantages of FUCOM in relation to the existing multi-criteria decision-making (MCDM) methods are as follows: (1) a significantly smaller number of pairwise comparisons (only n − 1), (2) a consistent pairwise comparison of criteria, and (3) the calculation of the reliable values of criteria weight coefficients, which contribute to rational judgment.

A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes1–7. Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumour types8. Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions—as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2–7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and—in liver cancer—frequently activate the telomerase gene TERT. A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act. Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

BackgroundSince the emergence of social media in 2004, a growing percentage of patients use this technology for health related reasons. To reflect on the alleged beneficial and potentially harmful effects of social media use by patients, the aim of this paper is to provide an overview of the extant literature on the effects of social media use for health related reasons on patients and their relationship with healthcare professionals.MethodsWe conducted a systematic literature review on empirical research regarding the effects of social media use by patients for health related reasons. The papers we included met the following selection criteria: (1) published in a peer-reviewed journal, (2) written in English, (3) full text available to the researcher, (4) contain primary empirical data, (5) the users of social media are patients, (6) the effects of patients using social media are clearly stated, (7) satisfy established quality criteria.ResultsInitially, a total of 1,743 articles were identified from which 22 were included in the study. From these articles six categories of patients’ use of social media were identified, namely: emotional, information, esteem, network support, social comparison and emotional expression. The types of use were found to lead to seven identified types of effects on patients, namely improved self-management and control, enhanced psychological well-being, and enhanced subjective well-being, diminished subjective well-being, addiction to social media, loss of privacy, and being targeted for promotion. Social media use by patients was found to affect the healthcare professional and patient relationship, by leading to more equal communication between the patient and healthcare professional, increased switching of doctors, harmonious relationships, and suboptimal interaction between the patient and healthcare professional.ConclusionsOur review provides insights into the emerging utilization of social media in healthcare. In particular, it identifies types of use by patients as well as the effects of such use, which may differ between patients and doctors. Accordingly, our results framework and propositions can serve to guide future research, and they also have practical implications for healthcare providers and policy makers.