Clinical evaluation of an anatomy-based patient specific quality assurance system

The Delta4DVH Anatomy 3D quality assurance (QA) system (ScandiDos), which converts the measured detector dose into the dose distribution in the patient geometry was evaluated. It allows a direct comparison of the calculated 3D dose with the measured back-projected dose. In total, 16 static and 16 volumetric-modulated arc therapy (VMAT) fields were planned using four different energies. Isocenter dose was measured with a pinpoint chamber in homogeneous phantoms to investigate the dose prediction by the Delta4DVH Anatomy algorithm for static fields. Dose distributions of VMAT fields were measured using GAFCHROMIC film. Gravitational gantry errors up to 10° were introduced into all VMAT plans to study the potential of detecting errors. Additionally, 20 clinical treatment plans were verified. For static fields, the Delta4DVH Anatomy predicted the isocenter dose accurately, with a deviation to the measured phantom dose of 1.1% ± 0.6%. For VMAT fields the predicted Delta4DVH Anatomy dose in the isocenter plane corresponded to the measured dose in the phantom, with an average gamma agreement index (GAI) (3 mm/3%) of 96.9± 0.4%. The Delta4DVH Anatomy detected the induced systematic gantry error of 10° with a relative GAI (3 mm/3%) change of 5.8% ± 1.6%. The conventional Delta4PT QA system detected a GAI change of 4.2%± 2.0%. The conventional Delta4PT GAI (3 mm/3%) was 99.8% ± 0.4% for the clinical treatment plans. The mean body and PTV-GAI (3 mm/5%) for the Delta4DVH Anatomy were 96.4% ± 2.0% and 97.7%± 1.8%; however, this dropped to 90.8%± 3.4% and 87.1% ± 4.1% for passing criteria of 3 mm/3%. The anatomy-based patient specific quality assurance system predicts the dose distribution correctly for a homogeneous case. The limiting factor for the error detection is the large variability in the error-free plans. The dose calculation algorithm is inferior to that used in the TPS (Eclipse)

Diffuse idiopathic skeletal hyperostosis: Etiology and clinical relevance

Diffuse idiopathic skeletal hyperostosis (DISH) is a systemic bone-forming condition characterized by the presence of at least three bony bridges at the anterolateral spine. The aim of this review was to address the present state of pathophysiological knowledge, the clinical relevance, and diagnosis of DISH. The pathogenesis of DISH is currently unknown. The presence of DISH has been associated with older age, male sex, obesity, hypertension, atherosclerosis, and diabetes mellitus. Because the new bone forms mainly at entheseal sites, local fibroblasts, chondrocytes, collagen fibers, and calcified matrix are probably influenced by genetic, vascular, metabolic, and mechanical factors. Diagnosing the presence of DISH is of clinical importance, because the risk of a spinal fracture increases and associations with the metabolic syndrome, coronary and aortic disease, and respiratory effects are strong. Unravelling the pathogenesis of DISH can impact the field of regenerative medicine and bone tissue regeneration

Diagnosis of diffuse idiopathic skeletal hyperostosis with chest computed tomography:inter-observer agreement

To evaluate and improve the interobserver agreement for the CT-based diagnosis of diffuse idiopathic skeletal hyperostosis (DISH). Six hundred participants of the CT arm of a lung cancer screening trial were randomly divided into two groups. The first 300 CTs were scored by five observers for the presence of DISH based on the original Resnick criteria for radiographs. After analysis of the data a consensus meeting was organised and the criteria were slightly modified regarding the definition of 'contiguous', the definition of 'flowing ossifications' and the viewing plane and window level. Subsequently, the second set of 300 CTs was scored by the same observers. kappa >= 0.61 was considered good agreement. The 600 male participants were on average 63.5 (SD 5.3) years old and had smoked on average 38.0 pack-years. In the first round kappa values ranged from 0.32 to 0.74 and 7 out of 10 values were below 0.61. After the consensus meeting the interobserver agreement ranged from 0.51 to 0.86 and 3 out of 10 values were below 0.61. The agreement improved significantly. This is the first study that reports interobserver agreement for the diagnosis of DISH on chest CT, showing mostly good agreement for modified Resnick criteria. . DISH is diagnosed on fluoroscopic and radiographic examinations using Resnick criteria . Evaluation of DISH on chest CT was modestly reproducible with the Resnick criteria . A consensus meeting and Resnick criteria modification improved inter-rater reliability for DISH . Reproducible CT criteria for DISH aids research into this poorly understood entity

A vitamin D, calcium and leucine-enriched whey protein nutritional supplement improves measures of bone health in sarcopenic non-malnourished older adults: The PROVIDE study

Alterations in musculoskeletal health with advanced age contribute to sarcopenia and decline in bone mineral density (BMD) and bone strength. This decline may be modifiable via dietary supplementation. To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of bone health. Participants (n 380) were participants of the PROVIDE study, a 13-week, multicenter, randomized, controlled, double-blind, 2 parallel-group study among non-malnourished older participants (≥ 65 years) with sarcopenia [determined by Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index (SMI; skeletal muscle mass/BW × 100) ≤ 37% in men and ≤ 28% in women using bioelectric impedance analysis] Supplementation of a vitamin D, calcium and leucine-enriched whey protein drink that comprises a full range of micronutrients (active; 2/day) was compared with an iso-caloric control. Serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), biochemical markers of bone formation (osteocalcin; OC, procollagen type 1 amino-terminal propeptide; P1NP) and resorption (carboxy-terminal collagen crosslinks; CTX), insulin like growth factor 1 (IGF-1) and total-body BMD were analysed pre- and post-intervention. Serum 25(OH)D concentrations increased from 51.1 ± 22.9 nmol/L (mean ± SD) to 78.9 ± 21.1 nmol/L in the active group (p < 0.001 vs. control). Serum PTH showed a significant treatment difference (p < 0.001) with a decline in the active group, and increase in the control group. Serum IGF-1 increased in the active group (p < 0.001 vs. control). Serum CTX showed a greater decline in the active group (p = 0.001 vs. control). There were no significant differences in serum OC or P1NP between groups during the intervention. Total body BMD showed a small (0.02 g/cm2; ~ 2%) but significant increase in the active group after supplementation (p = 0.033 vs. control). Consuming a vitamin D, calcium and leucine-enriched whey protein supplement for 13 weeks improved 25(OH)D, suppressed PTH and had small but positive effects on BMD, indicative of improved bone health, in sarcopenic non-malnourished older adults

Effects of whey protein supplement in the elderly submitted to resistance training:systematic review and meta-analysis

Aim: We performed a systematic review to map the evidence and analyze the effect of whey protein supplementation in the elderly submitted to resistance training.  Methods: A comprehensive search on Medline, LILACS, EMBASE, and the Cochrane Library for relevant publications was conducted until August 2015. The terms used in the search were: “Resistance training”; “Whey protein”; “Elderly”.  Results: A total of 632 studies were screened. Five studies were included composing a sample of 391 patients. The supplement whey protein was associated with higher total protein ingestion 9.40 (95% CI: 4.03–14.78), and with an average change in plasma leucine concentration. The supplementation was also associated with increased mixed muscle protein synthesis 1.26 (95% CI: 0.46–2.07) compared to the control group.  Conclusion: We observed an increase in total protein intake, resulting in increased concentration of leucine and mixed muscle protein fractional synthesis rate

Clinical, radiological, and patient-reported outcomes 13 years after pedicle screw fixation with balloon-assisted endplate reduction and cement injection

Purpose: In management of traumatic thoracolumbar burst fractures, short-segment pedicle screw fixation with balloon-assisted endplate reduction (BAER) and cement injection is a safe, feasible, and effective technique to maintain radiological alignment with minimum spinal segments involved. However, 20% of patients report daily discomfort despite good spinal alignment and fusion after this technique. This study provides clinical, radiological, and patient-reported outcomes after a minimum 13 years of follow-up. Methods: Eighteen patients were invited at the outpatient clinic for clinical/radiological examinations. The cohort (originally 20 patients) was treated 13–14 years earlier with pedicle screw fixation, BAER, and cement injection for traumatic thoracolumbar burst fractures. Patient-reported outcome measures were obtained at time of examinations. Current data were compared with data obtained at 6 years of follow-up. Results: Seventeen patients (median age 50; range 32–80) cooperated. No/minimal back pain was reported by 15 patients, and 12 patients returned to their previous heavy labor work. Median visual analog score of health (80%; 50–100%) was similar to results at 6 years (80%; 60–100% p = 0.259). An Oswestry Disability Index score of less than 20% (reflecting minimal disability) was reported by 14 patients, compared with 15 patients at 6 years of follow-up. No significant differences were found in wedge or Cobb angle between the time points. Intravertebral cement resorption was not observed. Conclusion: Results from this study suggest that, 13 years after pedicle screw fixation with BAER and cement injection for traumatic thoracolumbar burst fractures, functional performance, pain and radiological outcomes of the current cohort were stable or had slightly improved. Graphic abstract: These slides can be retrieved under Electronic Supplementary Material.[Figure not available: see fulltext.]

Interaction between genetic and epigenetic variation defines gene expression patterns at the asthma-associated locus 17q12-q21 in lymphoblastoid cell lines

Phenotypic variation results from variation in gene expression, which is modulated by genetic and/or epigenetic factors. To understand the molecular basis of human disease, interaction between genetic and epigenetic factors needs to be taken into account. The asthma-associated region 17q12-q21 harbors three genes, the zona pellucida binding protein 2 (ZPBP2), gasdermin B (GSDMB) and ORM1-like 3 (ORMDL3), that show allele-specific differences in expression levels in lymphoblastoid cell lines (LCLs) and CD4+ T cells. Here, we report a molecular dissection of allele-specific transcriptional regulation of the genes within the chromosomal region 17q12-q21 combining in vitro transfection, formaldehyde-assisted isolation of regulatory elements, chromatin immunoprecipitation and DNA methylation assays in LCLs. We found that a single nucleotide polymorphism rs4795397 influences the activity of ZPBP2 promoter in vitro in an allele-dependent fashion, and also leads to nucleosome repositioning on the asthma-associated allele. However, variable methylation of exon 1 of ZPBP2 masks the strong genetic effect on ZPBP2 promoter activity in LCLs. In contrast, the ORMDL3 promoter is fully unmethylated, which allows detection of genetic effects on its transcription. We conclude that the cis-regulatory effects on 17q12-q21 gene expression result from interaction between several regulatory polymorphisms and epigenetic factors within the cis-regulatory haplotype region

Familiäre Kavernome des Zentralnervensystems: Eine klinische und genetische Studie an 15 deutsche Familien

Zusammenfassung: 1928 beschrieb Hugo Friedrich Kufs erstmalig eine Familie mit zerebralen, retinalen und kutanen Kavernomen. Mittlerweile wurden über 300 weitere Familien beschrieben. Ebenfalls wurden drei Genloci 7q21-q22 (mit dem Gen CCM1), 7p15-p13 (Gen CCM2) und 3q25.2-q27 (Gen CCM3) beschrieben, in denen Mutationen zu Kavernomen führen. Das Genprodukt von CCM1 ist das Protein Krit1 (Krev Interaction Trapped 1), das über verschiedene Mechanismen mit der Angiogenese interagiert. Das neu entdeckte CCM2-Gen enkodiert ein Protein, das möglicherweise eine dem Krit1 ähnliche Funktion in der Regulation der Angiogenese hat. Das CCM3-Gen wurde noch nicht beschrieben. In dieser Arbeit werden sowohl die klinischen und genetischen Befunde bei 15 deutschen Familien beschriebe

A simple method for integrating a complex model into an ensemble data assimilation system using MPI

This paper details a strategy for modifying the source code of a complex model so that the model may be used in a data assimilation context, {and gives the standards for implementing a data assimilation code to use such a model}. The strategy relies on keeping the model separate from any data assimilation code, and coupling the two through the use of Message Passing Interface (MPI) {functionality}. This strategy limits the changes necessary to the model and as such is rapid to program, at the expense of ultimate performance. The implementation technique is applied in different models with state dimension up to $2.7 \times 10^8$. The overheads added by using this implementation strategy in a coupled ocean-atmosphere climate model are shown to be an order of magnitude smaller than the addition of correlated stochastic random errors necessary for some nonlinear data assimilation techniques