Description: The formation of epicormic sprouts on the boles of trees is a phenomenon that has, until recently, been poorly understood. Renewed interest in the topic in the last two decades has led to significant advances in our knowledge of the subject, especially in regard to bud anatomy, morphology and ontogeny. There exists, however, no comprehensive synthesis of results from different disciplines across genera and geographical areas; this review seeks to fill that void and provide a comprehensive framework capable of guiding future research. A tree's potential for producing epicormic branches is dependent on the number of buds that are produced on a growing shoot, the development of those buds and associated meristems over time and the factors that promote sprout formation or bud death. Based on the descriptions of a limited number of researched species, we were able to describe four different developmental strategies for epicormics based on characteristics of meristem development. Control over epicormic bud dormancy is complex, but it is clear that the traditional view of auxin-mediated dormancy release is incomplete. Genetic control over epicormic development is yet to be empirically proven. Future research should focus on clarifying these physiological and genetic controls of epicormic bud development as well as developing more robust methods for tracking epicormics in ecological and silvicultural studies.

Description: We examined the effects of partial harvesting on the successional and structural development of forest stands relative to an unmanaged relict stand in Quercus -dominated forests in Indiana, USA over an 84-year period. Despite abundant ingrowth of shade-tolerant Acer and Ulmus species into the understorey of all stands, the double-harvest stand exhibited greater increases in richness, diversity and species mingling among strata relative to the relict stand. The release of mid-tolerant genera, Carya and Fraxinus , through overstorey disturbance, resulted in species composition more akin to earlier stages of stand development. Within the relict forest individuals from mid-tolerant species became more aggregated over time, but in the double-harvest stand they became less aggregated. Differences between stands were related to the degree of overstorey disturbance; from the relict, to the double-harvest stand, we observed consistent patterns among multiple measures. Retrogression of stand succession was evident based on stand structure over time and functional resilience to overstorey disturbance was reflected in mid-seral, mast-producing species composition. This study highlights the long-term influence of understorey vegetation on stand compositional and structural development, and the potential to achieve greater diversity in forest composition and structure in forest ecosystems prone to species homogenization due to lack of disturbance.

Description: Background The combination of aflibercept with FOLFIRI has been shown to significantly prolong overall survival in patients with metastatic colorectal cancer (mCRC) after progression on oxaliplatin-based therapy. This trial evaluated the addition of aflibercept to oxaliplatin-based first-line treatment of patients with mCRC. Patients and methods Patients with mCRC were randomized to receive first-line therapy with mFOLFOX6 plus aflibercept (4 mg/kg) or mFOLFOX6 alone. The primary end point of this phase II study was the progression-free survival (PFS) rate at 12 months in each arm. The analysis of efficacy between the arms was a pre-planned secondary analysis. Results Of 236 randomized patients, 227 and 235 patients were evaluable for the primary efficacy analysis and safety, respectively. The probabilities of being progression-free at 12 months were 25.8% [95% confidence interval (CI) 17.2–34.4] for the aflibercept/mFOLFOX6 arm and 21.2% (95% CI 12.2–30.3) for the mFOLFOX6 arm. The median PFS was 8.48 months (95% CI 7.89–9.92) for the aflibercept/mFOLFOX6 arm and 8.77 months (95% CI 7.62–9.27) for the mFOLFOX6 arm; the hazard ratio of aflibercept/mFOLFOX6 versus mFOLFOX6 was 1.00 (95% CI 0.74–1.36). The response rates were 49.1% (95% CI 39.7–58.6) and 45.9% (95% CI 36.4–55.7) for patients treated with and without aflibercept, respectively. The most frequent treatment-emergent grade 3/4 adverse events (AEs) excluding laboratory abnormalities reported for aflibercept/mFOLFOX6 versus mFOLFOX6 were neuropathy (16.8% versus 17.2%) and diarrhea (13.4% versus 5.2%). Neutropenia grade 3/4 occurred in 36.1% versus 29.3%. The most common vascular endothelial growth factor inhibition class-effect grade 3/4 AEs for aflibercept/mFOLFOX6 versus mFOLFOX6 were hypertension (35.3% versus 1.7%), proteinuria (9.2% versus 0%), deep vein thrombosis (5.9% versus 0.9%) and pulmonary embolism (5.9% versus 5.2%). Conclusion No difference in PFS rate was observed between treatment groups. Adding aflibercept to first-line mFOLFOX6 did not increase efficacy but was associated with higher toxicity. Clinical Trial Number NCT00851084, www.clinicaltrials.gov , EudraCT 2008-004178-41.

Description: Aims Using a network of permanent plots, we determined how multiple old-growth forests changed over an 18–19-year period at a state-wide scale. This examination of change allowed us to assess how the compositional and structural stability of each forest varied with site characteristics (topography, physiography and productivity) and stochastic disturbance. Methods In 2011, we resampled 150 plots distributed across five old-growth hardwood forests in Indiana, USA that were originally sampled in 1992–1993. Within each plot, we relocated and remeasured the diameter at breast height (dbh) of all trees (≥10.0cm) present during the 1992–1993 sample, which allowed us to track their individual fates through time for growth and mortality calculations. Trees that grew to ≥10.0cm dbh since plot establishment were designated as ingrowth. The dbh and species of all saplings (stems ≥2.0cm but 〈10.0cm dbh) were also recorded. For each forest, we calculated density (stems ha –1 ), basal area (BA; m 2 ha –1 ) and importance value (relative density + relative BA)/2) of trees by species. For saplings, density per ha was calculated by species for each forest. We also calculated annual mortality rate (AMR) for three diameter classes (10–29.9, 30–59.9 and ≥60cm) and species richness (S), evenness (E) and Shannon–Weiner diversity (H') for the tree and sapling layers. Differences between years were compared for each forest using paired t -tests and Wilcoxon signed rank tests. Important Findings Although we observed commonality in changes across some sites, our results suggest that these forests differ in their rates and trajectories of change. Changes in total stand BA and density varied across sites and were influenced by past disturbance and mortality rates. We observed a general increase in the overstory dominance of Acer saccharum coupled with a general decrease in the dominance of Quercus section Lobatae (red oak group) species. Mortality of overstory trees present in 1992–1993 ranged from 27% to 49% over the study period (mean AMR 1.6–3.7%). Most sites experienced greater mortality of early and mid-successional species, but one site experienced heavy mortality of Fagus grandifolia , a shade-tolerant late-successional species. Shade tolerant species, A. saccharum in particular, dominated the sapling layer at most sites. However, recruitment of this species into larger size classes did not occur uniformly across all sites and the species was comparatively uncommon at one site. Overall, our results suggest that old-growth remnants, even within a single state, cannot be viewed as equivalent units with regard to research or management. Stochastic disturbance events and surrounding land use may have amplified effects on small scattered remnants. Therefore, continued monitoring of these rare, but biologically important forests is critical to their long-term management and protection.

Description: Early successional stands composed of naturally regenerated hardwood and conifer species are abundant in the forests of northeastern North America. Substantial improvements in the composition and growth of these stands may be possible with early management intervention. Unfortunately, stand responses to early management inputs are poorly understood since many of these stands are rarely manipulated. We examined the response of early successional stands to combinations of two management intensities (with and without enrichment planting and different levels of vegetation control) and three compositional objectives (hardwood, mixedwood and conifer). The treatments were designed to represent management options available in the region, including hardwood thinning, conifer release and a combination of treatments to promote hardwood–conifer mixedwood stands. Seven years after treatment, yields of the two hardwood thinning treatments ranged from 43.4 to 56.6 Mg ha –1 , which were similar to the 52.9 Mg ha –1 yield of the untreated control but with 17 and 46% lower densities, respectively. In the conifer release treatments, the removal of hardwoods promoted conifer dominance and resulted in yields between 19.9 and 30.4 Mg ha –1 7 years after treatment. The conifer release treatments will likely be dominated by conifers in the future with varying hardwood densities due to hardwoods establishing in gaps without conifers. After 7 years, yields of the mixedwood treatments were between 19 and 47% greater than the conifer release treatments due to the retention of thinned hardwood stems and represent stands that dominate much of the forestland in the region. Results from this study demonstrated that early successional stands can be effectively managed during early stand development to improve growth and the longer term composition.

Description: The western rock lobster, Panulirus cygnus , provides Australia's most valuable wild caught fishery but, in recent years, there has been a dramatic decline in settlement of the post-larval phase into their natal coastal habitat. One hypothesis for this decline was that the oceanographic conditions no longer favour the survival, feeding and growth of the larval (phyllosoma) phase. To explore this, the oceanography and corresponding zooplankton prey field along five latitudinal transects in the south-eastern Indian Ocean were quantified during July 2010. Leeuwin Current Water (LCW) and Sub-Tropical Surface Water (STSW) were distinguished and a prominent front at ~30°S characterized by strong eastward flow separated them. Although zooplankton abundance increased towards the north, the prey field was unevenly distributed with patches of higher prey concentration associated mainly with LCW. Chaetognaths were the most abundant prey item (means: 17.2 and 4.1 m –3 in LCW and STSW, respectively) and were positively correlated with chlorophyll a in both water masses. Panulirus cygnus phyllosoma had a highly patchy distribution but, despite lower prey concentrations, were more abundant in STSW than LCW, particularly south of the front. Our results suggest that LC meso-scale features with strong fronts may be implicated in phyllosoma aggregations and shoreward transport of late-stage larvae and that this warrants further investigation.

Description: Herpes simplex virus type 2 (HSV-2) infection is associated with a 3-fold increase in the risk of human immunodeficiency virus (HIV) acquisition, perhaps through alterations in mucosal HIV-susceptible target cells. We performed a clinical trial to assess the impact of herpes therapy on cervical immunology in HSV-2–infected, HIV-uninfected women from Africa or the Caribbean who were living in Toronto, Canada. Thirty participants received 1 g of valacyclovir orally each day for 2 months in a randomized double-blind, placebo-controlled, crossover trial. Valacyclovir did not reduce the number of cervical CD4 + T cells, the number of dendritic cells, or the expression of proinflammatory cytokines and tended to increase the expression of the HIV coreceptor CCR5 and the activation marker CD69. Short-term valacyclovir therapy did not reverse HSV-2–associated alterations in genital immunology. Clinical Trials Registration . NCT00946556.

Description: Partial canopy cover promotes regeneration of many ecologically and/or economically favoured tree species in temperate mesic forests. However, the specific effects of belowground resource competition from different canopy strata in these systems are poorly understood. This is particularly the case for American chestnut ( Castanea dentata (Marsh.) Borkh.), a formerly dominant forest tree species in eastern North America that was functionally extirpated from the canopy by an exotic blight disease and for which there is now increased interest in forest restoration using blight-resistant backcross hybrids. We examined the influence of overstory and herbaceous root competition (via trenching or weeding) on growth and survival of 3-year-old, underplanted American chestnut and northern red oak ( Quercus rubra L.) seedlings following midstory removal. Leaf physiology was evaluated on American chestnut throughout the third growing season. Compared with northern red oak, American chestnut had greater relative aboveground growth and its relative growth was more responsive to the removal of overstory root competition. American chestnut had greater instantaneous water use efficiency in the absence of overstory root competition. Herbaceous root competition had no effect on seedling growth of either species. Thus, in low-light conditions typical of an incomplete canopy, overstory root competition and not herbaceous competition limited American chestnut seedling growth and physiological development during establishment.

Description: Systemic treatment for cutaneous T-cell lymphoma (CTCL) involves the use of less aggressive, well-tolerated therapies. Pralatrexate is a novel antifolate with high affinity for reduced folate carrier-1. A dose de-escalation strategy identified recommended pralatrexate dosing for patients with CTCL that demonstrated high activity, good rates of disease control, and an acceptable toxicity profile for continuous long-term dosing. Eligibility included mycosis fungoides, Sézary syndrome, or primary cutaneous anaplastic large cell lymphoma, with disease progression after ≥ 1 prior systemic therapy. The starting dose and schedule was 30 mg/m 2 /wk intravenously for 3 of 4 (3/4) weeks. Subsequent starting doses were 20, 15, and 10 mg/m 2 /wk for 3/4 or 2 of 3 (2/3) weeks. Response was evaluated by the modified severity-weighted adjustment tool. Fifty-four patients were treated. The recommended regimen was identified as 15 mg/m 2 /wk for 3/4 weeks and was explored in the expansion cohort. In 29 patients treated overall with the recommended dosing regimen, the median number of prior systemic therapies was 4. Pralatrexate was administered for a median of 4 cycles; response rate was 45%. The most common grade 3 adverse event (AE) was mucositis (17%); the only grade 4 AE was leukopenia (3%). Pralatrexate 15 mg/m 2 /wk for 3/4 weeks shows high activity with acceptable toxicity in patients with relapsed/refractory CTCL.