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\"Evolution investigates each of our ancestors in detail and in context, from the anatomy of their bones to the environment they lived in. Key fossil finds are showcased on double-page feature spreads. Detailed maps show where each species has been found and plot the gradual spread of humans around the world. The book has been fully updated to include the latest discoveries and research--including the newly discovered species Homo naledi--and presents the latest thinking on some of the most captivating questions in science, such as whether modern humans and Neanderthals interacted with each other. Written and authenticated by a team of acknowledged experts and illustrated by renowned Dutch paleoartists the Kennis brothers, Evolution presents the story of our species with unique richness, authority, and detail\"-- Provided by publisher.

Tenovin-6 (Tnv-6) is a bioactive small molecule with anti-neoplastic activity. Inhibition of the Sirtuin class of protein deacetylases with activation of p53 function is associated with the pro-apoptotic effects of Tnv-6 in many tumors. Here, we demonstrate that in chronic lymphocytic leukemia (CLL) cells, Tnv-6 causes non-genotoxic cytotoxicity, without adversely affecting human clonogenic hematopoietic progenitors in vitro , or murine hematopoiesis. Mechanistically, exposure of CLL cells to Tnv-6 did not induce cellular apoptosis or p53-pathway activity. Transcriptomic profiling identified a gene program influenced by Tnv-6 that included autophagy-lysosomal pathway genes. The dysregulation of autophagy was confirmed by changes in cellular ultrastructure and increases in the autophagy-regulatory proteins LC3 (LC3-II) and p62/Sequestosome. Adding bafilomycin-A1, an autophagy inhibitor to Tnv-6 containing cultures did not cause synergistic accumulation of LC3-II, suggesting inhibition of late-stage autophagy by Tnv-6. Thus, in CLL, the cytotoxic effects of Tnv-6 result from dysregulation of protective autophagy pathways.

Risk stratification is critical in the care of patients with myelodysplastic syndromes (MDS). Approximately 10% have a complex karyotype (CK), defined as more than two cytogenetic abnormalities, which is a highly adverse prognostic marker. However, CK-MDS can carry a wide range of chromosomal abnormalities and somatic mutations. To refine risk stratification of CK-MDS patients, we examined data from 359 CK-MDS patients shared by the International Working Group for MDS. Mutations were underrepresented with the exception of TP53 mutations, identified in 55% of patients. TP53 mutated patients had even fewer co-mutated genes but were enriched for the del(5q) chromosomal abnormality (p < 0.005), monosomal karyotype (p < 0.001), and high complexity, defined as more than 4 cytogenetic abnormalities (p < 0.001). Monosomal karyotype, high complexity, and TP53 mutation were individually associated with shorter overall survival, but monosomal status was not significant in a multivariable model. Multivariable survival modeling identified severe anemia (hemoglobin < 8.0 g/dL), NRAS mutation, SF3B1 mutation, TP53 mutation, elevated blast percentage (>10%), abnormal 3q, abnormal 9, and monosomy 7 as having the greatest survival risk. The poor risk associated with CK-MDS is driven by its association with prognostically adverse TP53 mutations and can be refined by considering clinical and karyotype features.

Following sciatic nerve transection in adult rats, a proportion of injured dorsal root ganglion (DRG) neurons die, through apoptosis, over the following 6 months. Previous studies showed that axotomy and neurotrophin-3 administration may have effects on expression of neurotrophins and their receptors in DRG. In the current study, the fourth and fifth lumbar DRGs of rats were examined 2 weeks after right sciatic nerve transection and ligation. The effects of axotomy and systemic NT-3 treatment on neuronal genes were investigated by microarray. The results demonstrated that bone morphogenetic protein (BMP) and Janus protein tyrosine kinase signaling pathways are induced in axotomized DRG, and PI-3 kinase and BMP pathways and genes controlling various cellular functions were induced after axotomy and NT-3 administration.

Nurses experience verbal abuse as a nearly daily occurrence in the workplace. Sources of this abuse include patients and their families, visitors, physicians, managers and peers. A non-experimental, correlational study was undertaken to examine the contribution of latent constructs, individual characteristics and organizational characteristics, to the frequency with which registered nurses experience verbal abuse in the workplace. Several observed variables were identified to represent the latent constructs. Year in practice and position within the organization were the observed variables for the individual characteristics construct. Workplace aggression tolerance and violence prevention climate were the observed variables for the organizational characteristics construct. ANCC Magnet® status was an observed variable shared by both latent constructs. The sample was composed of 256 registered nurses from the states of Maryland, Virginia and West Virginia. Participants were recruited through mailing lists from state Boards of Nursing and were asked to complete an anonymous survey. IRB approval was obtained for the study. Findings of the study indicated: (1) A statistically significant, moderately strong effect for the organizational characteristics construct and a non-significant weak effect for the individual characteristics construct on the outcome variable of verbal abuse frequency. (2) The four observed variables: years in practice, organizational position; workplace aggression tolerance; and violence prevention climate behaved as predicted and had moderately strong effects for the latent constructs. (3) ANCC Magnet® status did not behave as predicted and was not significantly related to either latent construct. The findings of the study indicated that verbal abuse of registered nurses may most effectively be reduced through attention to the characteristics or culture of the organization versus attempts to intervene with individual nurses.

Quality in the Manufacture of Medicines and Other Healthcare Products by J. Sharp is reviewed.

Pharmaceutical Emulsions and Suspensions by F. Nielloud and G. Marti-Mestres, Eds. is reviewed.