Strain driven fast osseointegration of implants

BACKGROUND: Although the bone's capability of dental implant osseointegration has clinically been utilised as early as in the Gallo-Roman population, the specific mechanisms for the emergence and maintenance of peri-implant bone under functional load have not been identified. Here we show that under immediate loading of specially designed dental implants with masticatory loads, osseointegration is rapidly achieved. METHODS: We examined the bone reaction around non- and immediately loaded dental implants inserted in the mandible of mature minipigs during the presently assumed time for osseointegration. We used threaded conical titanium implants containing a titanium2+ oxide surface, allowing direct bone contact after insertion. The external geometry was designed according to finite element analysis: the calculation showed that physiological amplitudes of strain (500–3,000 ustrain) generated through mastication were homogenously distributed in peri-implant bone. The strain-energy density (SED) rate under assessment of a 1 Hz loading cycle was 150 Jm-3 s-1, peak dislocations were lower then nm. RESULTS: Bone was in direct contact to the implant surface (bone/implant contact rate 90%) from day one of implant insertion, as quantified by undecalcified histological sections. This effect was substantiated by ultrastructural analysis of intimate osteoblast attachment and mature collagen mineralisation at the titanium surface. We detected no loss in the intimate bone/implant bond during the experimental period of either control or experimental animals, indicating that immediate load had no adverse effect on bone structure in peri-implant bone. CONCLUSION: In terms of clinical relevance, the load related bone reaction at the implant interface may in combination with substrate effects be responsible for an immediate osseointegration state

Statistical challenges in the development and evaluation of marker-based clinical tests

Exciting new technologies for assessing markers in human specimens are now available to evaluate unprecedented types and numbers of variations in DNA, RNA, proteins, or biological structures such as chromosomes. These markers, whether viewed individually, or collectively as a 'signature', have the potential to be useful for disease risk assessment, screening, early detection, prognosis, therapy selection, and monitoring for therapy effectiveness or disease recurrence. Successful translation from basic research findings to clinically useful test requires basic, translational, and regulatory sciences and a collaborative effort among individuals with varied types of expertise including laboratory scientists, technology developers, clinicians, statisticians, and bioinformaticians. The focus of this commentary is the many statistical challenges in translational marker research, specifically in the development and validation of marker-based tests that have clinical utility for therapeutic decision-making

Evaluation of cytokine responses against novel Mtb antigens as diagnostic markers for TB disease.

OBJECTIVE: We investigated the accuracy of host markers detected in Mtb antigen-stimulated whole blood culture supernatant in the diagnosis of TB. METHODS: Prospectively, blood from 322 individuals with presumed TB disease from six African sites was stimulated with four different Mtb antigens (Rv0081, Rv1284, ESAT-6/CFP-10, and Rv2034) in a 24 h whole blood stimulation assay (WBA). The concentrations of 42 host markers in the supernatants were measured using the Luminex multiplex platform. Diagnostic biosignatures were investigated through the use of multivariate analysis techniques. RESULTS: 17% of the participants were HIV infected, 106 had active TB disease and in 216 TB was excluded. Unstimulated concentrations of CRP, SAA, ferritin and IP-10 had better discriminating ability than markers from stimulated samples. Accuracy of marker combinations by general discriminant analysis (GDA) identified a six analyte model with 77% accuracy for TB cases and 84% for non TB cases, with a better performance in HIV uninfected patients. CONCLUSIONS: A biosignature of 6 cytokines obtained after stimulation with four Mtb antigens has moderate potential as a diagnostic tool for pulmonary TB disease individuals and stimulated marker expression had no added value to unstimulated marker performance

Entanglement of Imaging and Imagining of Nanotechnology

Images, ranging from visualizations of the nanoscale to future visions, abound within and beyond the world of nanotechnology. Rather than the contrast between imaging, i.e. creating images that are understood as offering a view on what is out there, and imagining, i.e. creating images offering impressions of how the nanoscale could look like and images presenting visions of worlds that might be realized, it is the entanglement between imaging and imagining which is the key to understanding what images do. Three main arenas of entanglement of imag(in)ing and the tensions involved are discussed: production practices and use of visualizations of the nanoscale; imag(in)ing the future and the present; and entanglements of nanoscience and art. In these three arenas one sees struggles about which images might stand for nanotechnology, but also some stabilization of the entanglement of imag(in)ing, for example in established rules in the practices of visualizing the nanoscale. Three images have become iconic, through the combination of their wide reception and further circulation. All three, the IBM logo, the Foresight Institute’s Nanogear image, and the so-called Nanolouse, depict actual or imagined technoscientific objects and are thus seen as representing technoscientific achievements – while marking out territory

The Generation R Study Biobank: a resource for epidemiological studies in children and their parents

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health from fetal life until young adulthood. In total, 9,778 mothers were enrolled in the study. Prenatal and postnatal data collection is conducted by physical examinations, questionnaires, interviews, ultrasound examinations and biological samples. Major efforts have been conducted for collecting biological specimens including DNA, blood for phenotypes and urine samples. In this paper, the collection, processing and storage of these biological specimens are described. Together with detailed phenotype measurements, these biological specimens form a unique resource for epidemiological studies focused on environmental exposures, genetic determinants and their interactions in relation to growth, health and development from fetal life onwards

Evaluation of biological pathways involved in chemotherapy response in breast cancer

INTRODUCTION: Our goal was to examine the association between biological pathways and response to chemotherapy in estrogen receptor-positive (ER+) and ER-negative (ER-) breast tumors separately. METHODS: Gene set enrichment analysis including 852 predefined gene sets was applied to gene expression data from 51 ER- and 82 ER+ breast tumors that were all treated with a preoperative paclitaxel, 5-fluoruracil, doxorubicin, and cyclophosphamide chemotherapy. RESULTS: Twenty-seven (53%) ER- and 7 (9%) ER+ patients had pathologic complete response (pCR) to therapy. Among the ER- tumors, a proliferation gene signature (false discovery rate [FDR] q = 0.1), the genomic grade index (FDR q = 0.044), and the E2F3 pathway signature (FDR q = 0.22, P = 0.07) were enriched in the pCR group. Among the ER+ tumors, the proliferation signature (FDR q = 0.001) and the genomic grade index (FDR q = 0.015) were also significantly enriched in cases with pCR. Ki67 expression, as single gene marker of proliferation, did not provide the same information as the entire proliferation signature. An ER-associated gene set (FDR q = 0.03) and a mutant p53 gene signature (FDR q = 0.0019) were enriched in ER+ tumors with residual cancer. CONCLUSION: Proliferation- and genomic grade-related gene signatures are associated with chemotherapy sensitivity in both ER- and ER+ breast tumors. Genes involved in the E2F3 pathway are associated with chemotherapy sensitivity among ER- tumors. The mutant p53 signature and expression of ER-related genes were associated with lower sensitivity to chemotherapy in ER+ breast tumors only.Journal ArticleResearch Support, N.I.H. ExtramuralResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Assessing Specific Cognitive Deficits Associated with Dementia in Older Adults with Down Syndrome: Use and Validity of the Arizona Cognitive Test Battery (ACTB)

BACKGROUND: Down syndrome is associated with specific cognitive deficits. Alongside this, older adults with Down syndrome are a high risk group for dementia. The Arizona Cognitive Test Battery (ACTB), a cognitive assessment battery specifically developed for use with individuals with Down syndrome, has been proposed for use as outcome measures for clinical trials in this population. It has not been validated in older adults with Down syndrome. This study aims to assess the use and validity of the ACTB in older adults with Down syndrome. METHODS: Participants with Down syndrome aged 45 and over were assessed using the ACTB, standard tabletop tests and informant ratings. RESULTS: Assessment outcomes of 49 participants were analysed. Of these, 19 (39%) had a diagnosis of dementia or possible dementia. Most participants were able to attempt most of the tasks, although some tasks had high floor effects (including CANTAB Intra-Extra Dimensional shift stages completed and Modified Dots Task). Of the ACTB tasks, statistically significant differences were observed between the dementia and no dementia groups on CANTAB Simple Reaction Time median latency, NEPSY Visuomotor Precision-Car and Motorbike and CANTAB Paired Associates Learning stages completed. No significant differences were observed for CANTAB Intra-Extra Dimensional Shift, Modified Dots Task, Finger Sequencing, NEPSY Visuomotor precision-Train and Car and CANTAB Paired Associates Learning first trial memory score. Several of the tasks in the ACTB can be used in older adults with Down syndrome and have mild to moderate concurrent validity when compared to tabletop tests and informant ratings, although this varies on a test by test basis. CONCLUSIONS: Overall, scores for a number of tests in the ACTB were similar when comparing dementia and no dementia groups of older adults with Down syndrome, suggesting that it would not be an appropriate outcome measure of cognitive function for clinical trials of dementia treatments without further modification and validation