Focusing light through a free-form scattering medium

Imaging and transport light through scattering opaque media is a hot topic pursued in multiple fields, ranging from nanotechnology to life sciences. A promising technique to do this is wavefront shaping (WFS), where the light propagation through a scattering medium is controlled by interference [1][2]. Recently, the potential of WFS was even extended to, for instance, time-varying samples [3][4]. In most cases to date, WFS has been done on the quintessential scattering sample geometry, namely in slabs. Real-world applications, however, require samples to have any shape – “free-form scattering optics” – that defies current theories. Here, we present the study of an opaque sample of TiO2 particles suspended in silicone. Exploiting the flexibility of silicone, we are able to modify the geometry of the sample and measure the enhancement of the intensity η in a point of the speckle pattern. Using this opportunity, we compare the performance of a flat and a free form sample. These experimental measurements will be compared with a newly formulated theory of light transport in free form scattering media

Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels\ud

Objectives: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of VWF and FVIII. Methods and Results: We genotyped the control populations of two population-based studies for four AVPR2 variations: a-245c, G12E, L309L, and S331S. Rare alleles of a-245c, G12E, and S331S, which were in linkage disequilibrium, were associated with higher VWF propeptide, VWF and FVIII levels. The functionality of the G12E variant was studied in stably transfected MDCKII cells, expressing constructs of either 12G-V2R or 12E-V2R. Both V2R variants were fully glycosylated and expressed on the basolateral membrane. The binding affinity of V2R for AVP was increased three-fold in 12E-V2R–green fluorescent protein (GFP) cells, which is in accordance with increased levels of VWF propeptide associated with the 12E variant. The dissociation constant (KD) was 4.5 nm [95% confidence interval (CI) 3.6–5.4] for 12E-V2R–GFP and 16.5 nm (95% CI 10.1–22.9) for 12G-V2R–GFP. AVP-induced cAMP generation was enhanced in 12E-V2R–GFP cells. Conclusions: The 12E-V2R variant has increased binding affinity for AVP, resulting in increased signal transduction, and is associated with increased levels of VWF propeptide, VWF, and FVII

Clinical findings just after return to play predict hamstring re-injury, but baseline MRI findings do not

__Abstract__ Background Acute hamstring re-injuries are common and hard to predict. The aim of this study was to investigate the association between clinical and imaging findings and the occurrence of hamstring re-injuries. Methods We obtained baseline data (clinical and MRI findings) of athletes who sustained an acute hamstring injury within 5 days of initial injury. We also collected data of standardised clinical tests within 7 days after return to play (RTP). The number of re-injuries was recorded within 12 months. We analysed the association between the possible predictive variables and re-injuries with a multivariate Cox proportional-hazards regression model. Results Eighty patients were included at baseline and 64 p

One-year follow-up of a randomised controlled trial on added splinting to eccentric exercises in chronic midportion Achilles tendinopathy

OBJECTIVE: The study examined whether the addition of a night splint to eccentric exercises is beneficial for functional outcome in chronic mid-portion Achilles tendinopathy. DESIGN: One-year follow-up of a randomised controlled single blinded clinical trial. SETTING: Sports medicine department in a general hospital. PATIENTS: 58 patients (70 tendons) were included. INTERVENTIONS: All patients completed a 12-week heavy load eccentric training programme. One group received a night splint in addition to eccentric exercises. Main outcome measurements: Outcome scores were: Victorian Institute of Sport Assessment - Achilles (VISA-A) score, subjective patient satisfaction and neovascularisation score measured with Power Doppler Ultrasonography. RESULTS: For both groups the VISA-A score increased significantly (from 50 to 76 (P < 0.01) in the eccentric group and from 49 to 78 (P < 0.01) in the night splint group). No significant differences in VISA-A score were found between the groups from baseline to one year (P = 0.32). Presence of neovessels at baseline did not predict change in VISA-A score after one year in the whole group (P = 0.71). CONCLUSION: Eccentric exercises with or without a night splint improved functional outcome at one-year follow-up. At follow-up there

Probability of detecting germline BRCA1/2 pathogenic variants in histological subtypes of ovarian carcinoma:A meta-analysis

Background: Histology restricted genetic predisposition testing of ovarian carcinoma patients is a topic of debate as the prevalence of BRCA1/2 pathogenic variants (PVs) in various histological subtypes is ambiguous. Our primary aim was to investigate the proportion of germline BRCA1/2 PVs per histological subtype. Additionally, we evaluated (i) proportion of somatic BRCA1/2 PVs and (ii) proportion of germline PVs in other ovarian carcinoma risk genes. Methods: PubMed, EMBASE and Web of Science were systematically searched and we included all studies reporting germline BRCA1/2 PVs per histological subtype. Pooled proportions were calculated using a random-effects meta-analysis model. Subsets of studies were used for secondary analyses. Results: Twenty-eight studies were identified. The overall estimated proportion of germline BRCA1/2 PVs was 16.8% (95% CI 14.6 to 19.2). Presence differed substantially among patients with varying histological subtypes of OC; proportions being highest in high-grade serous (22.2%, 95% CI 19.6 to 25.0) and lowest in clear cell (3.0%, 95% CI 1.6 to 5.6) and mucinous (2.5%, 95% CI 0.6 to 9.6) carcinomas. Somatic BRCA1/2 PVs were present with total estimated proportion of 6.0% (95% CI 5.0 to 7.3), based on a smaller subset of studies. Germline PVs in BRIP1, RAD51C, RAD51D, PALB2, and ATM were present in approximately 3%, based on a subset of nine studies. Conclusion: Germline BRCA1/2 PVs are most frequently identified in high-grade serous ovarian carcinoma patients, but are also detected in patients having ovarian carcinomas of other histological subtypes. Limiting genetic predisposition testing to high-grade serous ovarian carcinoma patients will likely be insufficient to identify all patients with a germline PV

Ultrasonographic tissue characterisation of human Achilles tendons: quantification of tendon structure through a novel non-invasive approach

OBJECTIVE: To asses if three-dimensional imaging of the Achilles tendon by Ultrasonographic Tissue Characterisation (UTC) can differentiate between symptomatic and asymptomatic tendons. DESIGN: Case-control study. SETTING: Sports medical department of The Hague medical centre. PATIENTS: Twenty-six tendons from patients with chronic midportion Achilles tendinopathy were included. The "matched" control group consisted of 26 asymptomatic tendons. INTERVENTIONS: Symptomatic and asymptomatic tendons were scanned using the UTC-procedure. One researcher performed the ultrasonographic data-collection. These blinded data were randomised and outcome measures were determined by two independent observers. Main outcome measurements: The raw ultrasonographic images were analysed with a custom-designed algorithm that quantifies the three-dimensional stability of echopatterns, qua intensity and distribution over contiguous transverse images. This three-dimensional stability was related to tendon structure in previous studies. UTC categorizes four different echo-types that represent: I) highly stable; II) medium stable; III) highly variable and IV) constantly low intensity and variable distribution. The percentages of echo-types were calculated and the maximum tendon-thickness was measured. Finally, the inter-observer reliability of UTC was determined. RESULTS: Symptomatic tendons showed less pixels in echo-types I and II than asymptomatic tendons (51.5% versus 76.6%, p<0.001), thus less three-dimensional stability of the echopattern. The mean maximum tendon thickness was 9.2 mm in the symptomatic group and 6.8 mm in the asymptomatic group (p<0.001). The Intra-class Correlation Coefficient (ICC) for the inter-observer reliability of determining the echo-types I+II was 0.95. The ICC for tendon thickness was 0.84. CONCLUSION: UTC can quantitatively evaluate tendon structure and thereby discriminate symptomatic and asymptomatic tendons. As such UTC might be useful to monitor treatment protocols

The most efficient and effective BRCA1/2 testing strategy in epithelial ovarian cancer:Tumor-First or Germline-First?

Objective: Genetic testing in epithelial ovarian cancer (OC) is essential to identify a hereditary cause like a germline BRCA1/2 pathogenic variant (PV). An efficient strategy for genetic testing in OC is highly desired. We evaluated costs and effects of two strategies; (i) Tumor-First strategy, using a tumor DNA test as prescreen to germline testing, and (ii) Germline-First strategy, referring all patients to the clinical geneticist for germline testing.Methods: Tumor-First and Germline-First were compared in two scenarios; using real-world uptake of testing and setting implementation to 100%. Decision analytic models were built to analyze genetic testing costs (including counseling) per OC patient and per family as well as BRCA1/2 detection probabilities. With a Markov model, the life years gained among female relatives with a germline BRCA1/2 PV was investigated.Results: Focusing on real-world uptake, with the Tumor-First strategy more OC patients and relatives with a germline BRCA1/2 PV are detected (70% versus 49%), at lower genetic testing costs (€1898 versus €2502 per patient, and €2511 versus €2930 per family). Thereby, female relatives with a germline BRCA1/2 PV can live on average 0.54 life years longer with Tumor-First compared to Germline-First. Focusing on 100% uptake, the genetic testing costs per OC patient are substantially lower in the Tumor-First strategy (€2257 versus €4986).Conclusions: The Tumor-First strategy in OC patients is more effective in identifying germline BRCA1/2 PV at lower genetic testing costs per patient and per family. Optimal implementation of Tumor-First can further improve detection of heredity in OC patients.</p