Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial.

Background: Effective maintenance therapies after chemoradiotherapy for lung cancer are lacking. Our aim was to investigate whether the MUC1 antigen-specific cancer immunotherapy tecemotide improves survival in patients with stage III unresectable non-small-cell lung cancer when given as maintenance therapy after chemoradiation.

Methods: The phase 3 START trial was an international, randomised, double-blind trial that recruited patients with unresectable stage III non-small-cell lung cancer who had completed chemoradiotherapy within the 4-12 week window before randomisation and received confirmation of stable disease or objective response.

Towards fabrication of 3D printed medical devices to prevent biofilm formation.

The use of three-dimensional (3D) printing technologies is transforming the way that materials are turned into functional devices. We demonstrate in the current study the incorporation of anti-microbial nitrofurantoin in a polymer carrier material and subsequent 3D printing of a model structure, which resulted in an inhibition of biofilm colonization. The approach taken is very promising and can open up new avenues to manufacture functional medical devices in the future.

The 3-year disease management effect: understanding the positive return on investment.

Objective: Conventional wisdom suggests that health promotion programs yield a positive return on investment (ROI) in year 3. In the case of the University of Minnesota's program, a positive ROI was achieved in the third year, but it was due entirely to the effectiveness of the disease management (DM) program. The objective of this study is to investigate why.

Retrospective cohort study of bronchial doses and radiation-induced atelectasis after stereotactic body radiation therapy of lung tumors located close to the bronchial tree.

Purpose: To evaluate the dose-response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose.

Methods And Materials: Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.

Extracellular norepinephrine clearance by the norepinephrine transporter is required for skeletal homeostasis.

Changes in bone remodeling induced by pharmacological and genetic manipulation of β-adrenergic receptor (βAR) signaling in osteoblasts support a role of sympathetic nerves in the regulation of bone remodeling. However, the contribution of endogenous sympathetic outflow and nerve-derived norepinephrine (NE) to bone remodeling under pathophysiological conditions remains unclear. We show here that differentiated osteoblasts, like neurons, express the norepinephrine transporter (NET), exhibit specific NE uptake activity via NET and can catabolize, but not generate, NE.

Indirect effects of human-induced environmental change on offspring production mediated by behavioural responses.

Human-induced rapid environmental changes often cause behavioural alterations in animals. The consequences that these alterations in turn have for the viability of populations are, however, poorly known. We used a population of threespine sticklebacks Gasterosteus aculeatus in the Baltic Sea to investigate the consequences of behavioural responses to human-induced eutrophication for offspring production.

Olfactory loss after head and neck cancer radiation therapy.

Background: A reduced sense of smell may be one explanation for why patients with cancer in the ear, nose and throat (ENT) region who are treated with radiation therapy lose weight. The purpose of this study was to investigate whether radiation therapy has a negative effect on olfactory function and, if so, whether this effect is dose-related.

Methodology: Seventy-one patients were tested using odour-detection sensitivity and olfactory identification tests before radiation therapy and 20 months after it.

An exploration of factors predicting malnutrition in patients with advanced head and neck cancer.

Objectives/hypothesis: Malnutrition is common among head and neck cancer patients and negatively impacts on survival and quality of life. This study aimed to identify predictors of malnutrition at time of diagnosis in order to identify patients at risk and enable early nutritional support and prevent malnutrition.

Materials And Method: A total of 134 patients with advanced oral and pharyngeal cancer were included in the study.

Osteo-promoting effects of insulin-like growth factor I (IGF-I) in a mouse model of type 1 diabetes.

Objective: Using a streptozotocin (STZ)-induced mouse model of type 1 diabetes (T1D), we have previously demonstrated that long-term diabetes inhibits regenerative bone formation during tibial distraction osteogenesis (DO) and perturbs skeletal integrity by decreasing cortical thickness, bone mineral density and bone's resistance to fracture. Because long-standing T1D is also associated with a deficiency of insulin-like growth factor I (IGF-I), we examined the effects of systemic IGF-I treatment on skeletal microarchitecture and strength, as well as on bone formation in diabetic mice.

Research Design And Methods: Streptozotocin-induced diabetic or control mice were treated with recombinant human IGF-I (rhIGF-I, 1.

Validation of quantitative bound- and pore-water imaging in cortical bone.

Purpose: To implement and validate a previously proposed ultra-short echo time method for measuring collagen-bound- and pore-water concentrations in bone based on their T2 differences.

Methods: Clinically compatible ultra-short echo time image sequences for quantitative T2 -based bound and pore-water imaging in bone were implemented and validated on a 3T human scanner and a 4.7T small bore system.

Prostate cancer metastases alter bone mineral and matrix composition independent of effects on bone architecture in mice--a quantitative study using microCT and Raman spectroscopy.

Prostate cancer is the most common primary tumor and the second leading cause of cancer-related deaths in men in the United States. Prostate cancer bone metastases are characterized by abnormal bone remodeling processes and result in a variety of skeletal morbidities. Prevention of skeletal complications is a crucial element in prostate cancer management.

Bmp2 in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells.

We generated a new Bmp2 conditional-knockout allele without a neo cassette that removes the Bmp2 gene from osteoblasts (Bmp2-cKO(ob)) using the 3.6Col1a1-Cre transgenic model. Bones of Bmp2-cKO(ob) mice are thinner, with increased brittleness.

The effect of consumer incentives on Medicaid beneficiaries' compliance with well-child visit guidelines.

The Affordable Care Act of 2010 recommends that consumer incentives be employed to increase the use of preventive care by Medicaid beneficiaries, but few evaluative studies exist. This study evaluates a Target gift card incentive employed by a Minnesota health plan serving Medicaid beneficiaries over the period 2002-2003. Lacking a contemporaneous control group, the proximity between the child's residence and the nearest Target store was used as the intervention variable.

Pellet formation of zygomycetes and immobilization of yeast.

Pelleted growth provides many advantages for filamentous fungi, including decreased broth viscosity, improved aeration, stirring, and heat transfer. Thus, the factors influencing the probability of pellet formation of Rhizopus sp. in a defined medium was investigated using a multifactorial experimental design.

Polarization control of Raman spectroscopy optimizes the assessment of bone tissue.

There is potential for Raman spectroscopy (RS) to complement tools for bone diagnosis due to its ability to assess compositional and organizational characteristics of both collagen and mineral. To aid this potential, the present study assessed specificity of RS peaks to the composition of bone, a birefringent material, for different degrees of instrument polarization. Specifically, relative changes in peaks were quantified as the incident light rotated relative to the orientation of osteonal and interstitial tissue, acquired from cadaveric femurs.

Biomechanical evaluation of physeal-sparing fixation methods in tibial eminence fractures.

Background: Tibial eminence fractures occur most commonly in skeletally immature children. Several techniques using physeal-sparing fracture fixation have been described, but their structural properties have not been evaluated.

Purpose: To determine the strength and resistance to displacement of physeal-sparing techniques used to fix tibial eminence fractures.

Partial removal of pore and loosely bound water by low-energy drying decreases cortical bone toughness in young and old donors.

With an ability to quantify matrix-bound and pore water in bone, (1)H nuclear magnetic resonance (NMR) relaxometry can potentially be implemented in clinical imaging to assess the fracture resistance of bone in a way that is independent of current X-ray techniques, which assess bone mineral density as a correlate of bone strength. Working towards that goal, we quantified the effect of partial dehydration in air on the mechanical and NMR properties of human cortical bone in order to understand whether NMR is sensitive to water-bone interactions at low energy and whether such interactions contribute to the age-related difference in the toughness of bone. Cadaveric femurs were collected from male and female donors falling into two age groups: 21-60 years of age (young) and 74-99 years of age (old).

Synergistic effect of exercise and statins on femoral strength in rats.

It is now widely recognized that in order to optimize bone health in the later years, bone healthy behaviors should begin at a young age and continue throughout life. Prescribed orally to lower lipid levels in adults of all ages, statins have also been shown to stimulate bone formation in vitro by promoting bone morphogenic protein-2 (BMP-2) activity and to stimulate bone formation in vivo. Weight bearing exercise is well known to stimulate bone formation through a mechanism whereby mechanical loading is 'sensed' by the mechano-sensors leading to a cascade of events involving the activation of osteoblasts.

A cost effectiveness analysis of stepped care treatment for bulimia nervosa.

Background: The cost effectiveness of various treatment strategies for bulimia nervosa (BN) is unknown.

Aims: To examine the cost effectiveness of stepped care treatment for BN.

Method: Randomized trial conducted at four clinical centers with intensive measurement of direct medical costs and repeated measurement of subject quality of life and family/significant other time involvement.

The impact of hyperfractionated radiotherapy regimen in patients with non-small cell lung cancer.

The prognosis for patients with lung cancer is poor with an average of 5-year overall survival rate of only 10-15 % taking all clinical stages together. The aim of this study was to elucidate the impact of the radiotherapy regimen on survival. Clinical data were collected from all the Swedish Oncology Departments for 1,287 patients with a diagnosed non-small cell lung cancer (NSCLC) subjected to curatively intended irradiation (≥50 Gy) during the years 1990 to 2000.

Silent information regulator (Sir)T1 inhibits NF-κB signaling to maintain normal skeletal remodeling.

Silent information regulator T1 (SirT1) is linked to longevity and negatively controls NF-κB signaling, a crucial mediator of survival and regulator of both osteoclasts and osteoblasts. Here we show that NF-κB repression by SirT1 in both osteoclasts and osteoblasts is necessary for proper bone remodeling and may contribute to the mechanisms linking aging and bone loss. Osteoclast- or osteoblast-specific SirT1 deletion using the Sirt(flox/flox) mice crossed to lysozyme M-cre and the 2.

Differential development of the distal and proximal femoral epiphysis and physis in mice.

Many pathologic conditions of hip development result from aberrant vascularity with subsequent effects on physeal resorption and epiphyseal fusion. To elucidate the mechanisms of these developmental disorders, researchers have mainly focused on larger mammals as they have been well characterized and are known to provide a model similar to humans in which a secondary ossification center is formed through an independent blood supply followed by physeal resorption. Murine models of hip development, however, have never been characterized as it was previously assumed that all physes in rodents never resorb and therefore not suitable as a model of the human condition.

Transforming growth factor β suppresses osteoblast differentiation via the vimentin activating transcription factor 4 (ATF4) axis.

ATF4 is an osteoblast-enriched transcription factor of the leucine zipper family. We recently identified that vimentin, a leucine zipper-containing intermediate filament protein, suppresses ATF4-dependent osteocalcin (Ocn) transcription and osteoblast differentiation. Here we show that TGFβ inhibits ATF4-dependent activation of Ocn by up-regulation of vimentin expression.

Interobserver delineation variation in lung tumour stereotactic body radiotherapy.

Objectives: In radiotherapy, delineation uncertainties are important as they contribute to systematic errors and can lead to geographical miss of the target. For margin computation, standard deviations (SDs) of all uncertainties must be included as SDs. The aim of this study was to quantify the interobserver delineation variation for stereotactic body radiotherapy (SBRT) of peripheral lung tumours using a cross-sectional study design.