Bayesian estimation of speciation and extinction from incomplete fossil occurrence data.

The temporal dynamics of species diversity are shaped by variations in the rates of speciation and extinction, and there is a long history of inferring these rates using first and last appearances of taxa in the fossil record. Understanding diversity dynamics critically depends on unbiased estimates of the unobserved times of speciation and extinction for all lineages, but the inference of these parameters is challenging due to the complex nature of the available data. Here, we present a new probabilistic framework to jointly estimate species-specific times of speciation and extinction and the rates of the underlying birth-death process based on the fossil record. The rates are allowed to vary through time independently of each other, and the probability of preservation and sampling is explicitly incorporated in the model to estimate the true lifespan of each lineage. We implement a Bayesian algorithm to assess the presence of rate shifts by exploring alternative diversification models. Tests on a range of simulated data sets reveal the accuracy and robustness of our approach against violations of the underlying assumptions and various degrees of data incompleteness. Finally, we demonstrate the application of our method with the diversification of the mammal family Rhinocerotidae and reveal a complex history of repeated and independent temporal shifts of both speciation and extinction rates, leading to the expansion and subsequent decline of the group. The estimated parameters of the birth-death process implemented here are directly comparable with those obtained from dated molecular phylogenies. Thus, our model represents a step towards integrating phylogenetic and fossil information to infer macroevolutionary processes.

Estimation of soil nitrate in the spring as a basis for adjustment of nitrogen fertiliser rates

Selostus: Maassa olevan nitraattitypen arviointi simulointimallin avulla

Trace element supplementation modulates pulmonary infection rates after major burns: a double-blind, placebo-controlled trial.

Infections remain the leading cause of death after major burns. Trace elements are involved in immunity and burn patients suffer acute trace element depletion after injury. In a previous nonrandomized study, trace element supplementation was associated with increased leukocyte counts and shortened hospital stays. This randomized, placebo-controlled trial studied clinical and immune effects of trace element supplements. Twenty patients, aged 40 +/- 16 y (mean +/- SD), burned on 48 +/- 17% of their body surfaces, were studied for 30 d after injury. They consumed either standard trace element intakes plus supplements (40.4 micromol Cu, 2.9 micromol Se, and 406 micromol Zn; group TE) or standard trace element intakes plus placebo (20 micromol Cu, 0.4 micromol Se, and 100 micromol Zn; group C) for 8 d. Demographic data were similar for both groups. Mean plasma copper and zinc concentrations were below normal until days 20 and 15, respectively (NS). Plasma selenium remained normal for group TE but decreased for group C (P < 0.05 on days 1 and 5). Total leukocyte counts tended to be higher in group TE because of higher neutrophil counts. Proliferation to mitogens was depressed compared with healthy control subjects (NS). The number of infections per patient was significantly (P < 0.05) lower in group TE (1.9 +/- 0.9) than in group C (3.1 +/- 1.1) because of fewer pulmonary infections. Early trace element supplementation appears beneficial after major burns; it was associated with a significant decrease in the number of bronchopneumonia infections and with a shorter hospital stay when data were normalized for burn size.

Protein-ligand binding free energy estimation using molecular mechanics and continuum electrostatics. Application to HIV-1 protease inhibitors.

A method is proposed for the estimation of absolute binding free energy of interaction between proteins and ligands. Conformational sampling of the protein-ligand complex is performed by molecular dynamics (MD) in vacuo and the solvent effect is calculated a posteriori by solving the Poisson or the Poisson-Boltzmann equation for selected frames of the trajectory. The binding free energy is written as a linear combination of the buried surface upon complexation, SASbur, the electrostatic interaction energy between the ligand and the protein, Eelec, and the difference of the solvation free energies of the complex and the isolated ligand and protein, deltaGsolv. The method uses the buried surface upon complexation to account for the non-polar contribution to the binding free energy because it is less sensitive to the details of the structure than the van der Waals interaction energy. The parameters of the method are developed for a training set of 16 HIV-1 protease-inhibitor complexes of known 3D structure. A correlation coefficient of 0.91 was obtained with an unsigned mean error of 0.8 kcal/mol. When applied to a set of 25 HIV-1 protease-inhibitor complexes of unknown 3D structures, the method provides a satisfactory correlation between the calculated binding free energy and the experimental pIC5o without reparametrization.

Afatinib versus placebo as adjuvant therapy after chemoradiation in a double-blind, phase III study (LUX-Head & Neck 2) in patients with primary unresected, clinically intermediate-to-high-risk head and neck cancer: study protocol for a randomized controlled trial.

BACKGROUND: Over 50% of patients with head and neck squamous cell carcinoma (HNSCC) present with locoregionally advanced disease. Those at intermediate-to-high risk of recurrence after definitive therapy exhibit advanced disease based on tumour size or lymph node involvement, non-oropharynx primary sites, human papillomavirus (HPV)-negative oropharyngeal cancer, or HPV-positive oropharynx cancer with smoking history (>10-pack-years). Non-surgical approaches include concurrent chemoradiotherapy, induction chemotherapy followed by definitive radiotherapy or chemoradiotherapy, or radiotherapy alone. Following locoregional therapies (including surgical salvage of residual cervical nodes), no standard intervention exists. Overexpression of epidermal growth factor receptor (EGFR), an ErbB family member, is associated with poor prognosis in HNSCC. EGFR-targeted cetuximab is the only targeted therapy that impacts overall survival and is approved for HNSCC in the USA or Europe. However, resistance often occurs, and new approaches, such as targeting multiple ErbB family members, may be required. Afatinib, an irreversible ErbB family blocker, demonstrated antiproliferative activity in preclinical models and comparable clinical efficacy with cetuximab in a randomized phase II trial in recurrent or metastatic HNSCC. LUX-Head & Neck 2, a phase III study, will assess adjuvant afatinib versus placebo following chemoradiotherapy in primary unresected locoregionally advanced intermediate-to-high-risk HNSCC. METHODS/DESIGN: Patients with primary unresected locoregionally advanced HNSCC, in good clinical condition with unfavourable risk of recurrence, and no evidence of disease after chemoradiotherapy will be randomized 2:1 to oral once-daily afatinib (40 mg starting dose) or placebo. As HPV status will not be determined for eligibility, unfavourable risk is defined as non-oropharynx primary site or oropharynx cancer in patients with a smoking history (>10 pack-years). Treatment will continue for 18 months or until recurrence or unacceptable adverse events occur. The primary endpoint measure is duration of disease-free survival; secondary endpoint measures are disease-free survival rate at 2 years, overall survival, health-related quality of life and safety. DISCUSSION: Given the unmet need in the adjuvant treatment of intermediate-to-high-risk HNSCC patients, it is expected that LUX-Head & Neck 2 will provide new insights into treatment in this setting and might demonstrate the ability of afatinib to significantly improve disease-free survival, compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov NCT01345669.

Source-wavelet estimation during full-waveform inversion of ground-penetrating radar data

A major issue in the application of waveform inversion methods to crosshole ground-penetrating radar (GPR) data is the accurate estimation of the source wavelet. Here, we explore the viability and robustness of incorporating this step into a recently published time-domain inversion procedure through an iterative deconvolution approach. Our results indicate that, at least in non-dispersive electrical environments, such an approach provides remarkably accurate and robust estimates of the source wavelet even in the presence of strong heterogeneity of both the dielectric permittivity and electrical conductivity. Our results also indicate that the proposed source wavelet estimation approach is relatively insensitive to ambient noise and to the phase characteristics of the starting wavelet. Finally, there appears to be little to no trade-off between the wavelet estimation and the tomographic imaging procedures.

Iowa Department for the Blind Performance Report, FY 2004

Agency Performance Report

Iowa Department for the Blind Performance Report, FY 2005

Agency Performance Report

Iowa Department for the Blind Performance Report, FY 2006

Agency Performance Report

Iowa Department for the Blind Performance Report, FY 2006

Agency Performance Report

Iowa Department for the Blind Performance Report, FY 2007

Agency Performance Report

Iowa Department for the Blind Performance Report, FY 2008

Agency Performance Report

Iowa Department for the Blind Performance Report, FY 2009

Agency Performance Report

Iowa Department for the Blind Performance Report, FY 2010

Agency Performance Report