Modern Modal Testing: A Cautionary Tale

Over the past 50 years, great advances have been achieved in both analytical modal analysis (i.e. finite element models and analysis) and experimental modal analysis (i.e. modal testing) in aerospace and other fields. With the advent of more powerful computers, higher performance instrumentation and data acquisition systems, and powerful linear modal extraction tools, analysts and test engineers have a breadth and depth of technical resources only dreamed of by our predecessors. However, some observed recent trends indicate that hard lessons learned are being forgotten or ignored, and possibly fundamental concepts are not being understood. These trends have the potential of leading to the degradation of the quality of and confidence in both analytical and test results. These trends are a making of our own doing, and directly related to having ever more powerful computers, programmatic budgetary pressures to limit analysis and testing, and technical capital loss due to the retirement of the senior component of a bimodal workforce. This paper endeavors to highlight some of the most important lessons learned, common pitfalls to hopefully avoid, and potential steps that may be taken to help reverse this trend

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L

Application of the LymphGen classification tool to 928 clinically and genetically-characterised cases of diffuse large B cell lymphoma (DLBCL).

We recently published results of targeted sequencing applied to 928 unselected cases of DLBCL registered in the Haematological Malignancy Research Network (HMRN) registry (1). Clustering allowed us to resolve five genomic subtypes. These subtypes shared considerable overlap with those proposed in two independent genomic studies(2, 3), suggesting the potential to use genetics to stratify patients by both risk and biology. In the original studies, clustering techniques were applied to sample cohorts to reveal molecular substructure, but left open the challenge of how to classify an individual patient. This was addressed by the LymphGen classification tool (4). LymphGen assigns an individual case to one of six molecular subtypes. The tool accommodates data from exome or targeted sequencing, either with or without copy number variant (CNV) data. Separate gene expression data allows classification of a seventh, MYC-driven subtype defined by a double hit (DHL) or molecular high-grade (MHG) gene expression signature(5-7).HR was funded by a studentship from the Medical Research Council. DH was supported by a Clinician Scientist Fellowship from the Medical Research Council (MR/M008584/1). The Hodson laboratory receives core funding from Wellcome and MRC to the Wellcome-MRC Cambridge Stem Cell Institute and core funding from the CRUK Cambridge Cancer Centre. HMRN is supported by BCUK 15037 and CRUK 18362

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.ope

Influence of bone density on implant stability parameters and implant success: a retrospective clinical study

<p>Abstract</p> <p>Background</p> <p>The aim of the present clinical study was to determine the local bone density in dental implant recipient sites using computerized tomography (CT) and to investigate the influence of local bone density on implant stability parameters and implant success.</p> <p>Methods</p> <p>A total of 300 implants were placed in 111 patients between 2003 and 2005. The bone density in each implant recipient site was determined using CT. Insertion torque and resonance frequency analysis were used as implant stability parameters. The peak insertion torque values were recorded with OsseoCare machine. The resonance frequency analysis measurements were performed with Osstell instrument immediately after implant placement, 6, and 12 months later.</p> <p>Results</p> <p>Of 300 implants placed, 20 were lost, meaning a survival rate of %. 93.3 after three years (average 3.7 ± 0.7 years). The mean bone density, insertion torque and RFA recordings of all 300 implants were 620 ± 251 HU, 36.1 ± 8 Ncm, and 65.7 ± 9 ISQ at implant placement respectively; which indicated statistically significant correlations between bone density and insertion torque values (p < 0.001), bone density and ISQ values (p < 0.001), and insertion torque and ISQ values (p < 0.001). The mean bone density, insertion torque and RFA values were 645 ± 240 HU, 37.2 ± 7 Ncm, and 67.1 ± 7 ISQ for 280 successful implants at implant placement, while corresponding values were 267 ± 47 HU, 21.8 ± 4 Ncm, and 46.5 ± 4 ISQ for 20 failed implants; which indicated statistically significant differences for each parameter (p < 0.001).</p> <p>Conclusion</p> <p>CT is a useful tool to determine the bone density in the implant recipient sites, and the local bone density has a prevailing influence on primary implant stability, which is an important determinant for implant success.</p

Robust penetrating microelectrodes for neural interfaces realized by titanium micromachining

Neural prosthetic interfaces based upon penetrating microelectrode devices have broadened our understanding of the brain and have shown promise for restoring neurological functions lost to disease, stroke, or injury. However, the eventual viability of such devices for use in the treatment of neurological dysfunction may be ultimately constrained by the intrinsic brittleness of silicon, the material most commonly used for manufacture of penetrating microelectrodes. This brittleness creates predisposition for catastrophic fracture, which may adversely affect the reliability and safety of such devices, due to potential for fragmentation within the brain. Herein, we report the development of titanium-based penetrating microelectrodes that seek to address this potential future limitation. Titanium provides advantage relative to silicon due to its superior fracture toughness, which affords potential for creation of robust devices that are resistant to catastrophic failure. Realization of these devices is enabled by recently developed techniques which provide opportunity for fabrication of high-aspect-ratio micromechanical structures in bulk titanium substrates. Details are presented regarding the design, fabrication, mechanical testing, in vitro functional characterization, and preliminary in vivo testing of devices intended for acute recording in rat auditory cortex and thalamus, both independently and simultaneously

Neuronal Deletion of Caspase 8 Protects against Brain Injury in Mouse Models of Controlled Cortical Impact and Kainic Acid-Induced Excitotoxicity

system. mice demonstrated superior survival, reduced seizure severity, less apoptosis, and reduced caspase 3 processing. Uninjured aged knockout mice showed improved learning and memory, implicating a possible role for caspase 8 in cognitive decline with aging.Neuron-specific deletion of caspase 8 reduces brain damage and improves post-traumatic functional outcomes, suggesting an important role for this caspase in pathophysiology of acute brain trauma