Programming balanced optical beam splitters in white paint

Wavefront shaping allows for ultimate control of light propagation in multiple-scattering media by adaptive manipulation of incident waves. We shine two separate wavefront-shaped beams on a layer of dry white paint to create two enhanced output speckle spots of equal intensity. We experimentally confirm by interference measurements that the output speckle spots are almost correlated like the two outputs of an ideal balanced beam splitter. The observed deviations from the phase behavior of an ideal beam splitter are analyzed with a transmission matrix model. Our experiments demonstrate that wavefront shaping in multiple-scattering media can be used to approximate the functionality of linear optical devices with multiple inputs and outputs

Differences between physicians in the likelihood of referral and acceptance of elderly patients for dialysis-influence of age and comorbidity

BACKGROUND: Incidence of dialysis in elderly patients in the Netherlands is low compared to other countries. This study aims to assess the impact of patients' age and comorbidity on the likelihood of referral and acceptance of patients for dialysis and whether this is affected by physician characteristics. METHODS: A vignette study was performed among 209 primary care physicians, 162 non-nephrology specialists and 20 nephrologists working in the north of the Netherlands. Physicians were offered six vignettes concerning case-reports of patients with end-stage renal disease (ESRD) and varying comorbidities or circumstances and asked about the likelihood of referral/acceptance of the patient in the given circumstances. RESULTS: The likelihood of referral within groups of physicians varied widely, especially within the group of primary care physicians and non-nephrology specialists, but was not affected by characteristics of physicians. The likelihood of referral or acceptance of patients for dialysis depended on the patient's age, and type and severity of comorbidity. In general, primary care physicians and non-nephrology specialists were less likely to refer than nephrologists were to accept. Differences within and between groups of physicians were larger for 80- than for 65-year-old patients, and for patients with less severe shortness of breath and cognitive impairments and more severe diabetes and social impairments. Hardly any differences were found for patients with cancer. CONCLUSION: Patients' age and comorbidities affect the likelihood of referral. Differences between groups of physicians suggest that there is insufficient agreement on the extent to which these factors should affect the referral/acceptance of patients for dialysis. These findings underline the need for more research into circumstances under which patients might benefit from dialysis. Guidelines should be developed to improve the referral of elderly and less healthy patients

Exploring New Ways to Improve Treatment Outcome of Colorectal Liver Metastases

Chemotherapeutic agents are part of the multimodality approach for treatment in patients with CRLM. The associated toxicity is major limitation to their use, and leads to early discontinuation of treatment. Therefore, the aim of the studies described in this thesis was to describe two experimental subjects to ameliorate chemotherapeutic treatment in the multi-modality approach of colorectal liver metastases: the impact on the circadian clock and dietary restriction

Disruption of clock gene expression in human colorectal liver metastases

The circadian timing system controls about 40 % of the transcriptome and is important in the regulation of a wide variety of biological processes including metabolic and proliferative functions. Disruption of the circadian clock could have significant effect on human health and has an important role in the development of cancer. Here, we compared the expression levels of core clock genes in primary colorectal cancer (CRC), colorectal liver metastases (CRLM), and liver tissue within the same patient. Surgical specimens of 15 untreated patients with primary CRC and metachronous CRLM were studied. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of 10 clock genes: CLOCK, BMAL1, PER1, PER2, PER3, CRY1, CRY2, CSNK1E, TIM, TIPIN, and 2 clock-controlled genes: Cyclin-D1, and WEE1. Expression levels of 7 core clock genes were downregulated in CRLM: CLOCK (p = 0.006), BMAL1 (p = 0.003), PER1 (p = 0.003), PER2 (p = 0.002), PER3 (p < 0.001), CRY1 (p = 0.002), and CRY2 (p < 0.001). In CRC, 5 genes were downregulated: BMAL1 (p = 0.02), PER1 (p = 0.004), PER2 (p = 0.008), PER3 (p < 0.001), and CRY2 (p < 0.001). CSNK1E was upregulated in CRC (p = 0.02). Cyclin-D1 and WEE1 were both downregulated in CRLM and CRC. Related to clinicopathological factors, a significant correlation was found between low expression of CRY1 and female gender, and low PER3 expression and the number of CRLM. Our data demonstrate that the core clock is disrupted in CRLM and CRC tissue from the same patient. This disruption may be linked to altered cell-cycle dynamics and carcinogenesis

The transcriptomic response to irinotecan in colon carcinoma bearing mice preconditioned by fasting

Background: Irinotecan use is limited due to severe toxicity. Preconditioning by fasting (PBF) protects against side effects of irinotecan while preserving its antitumor activity. The mechanisms underlying the effects of PBF still need to be elucidated. Here, we investigated the transcriptional responses of PBF on irinotecan in both tumor and healthy liver tissue. Experimental approach: Male BALB/c mice were subcutaneously injected with C26 colon carcinoma cells. Twelve days after tumor inoculation, two groups were fasted for three days and two groups were allowed food ad libitum (AL). Subsequently, both groups received one dose of irinotecan. Twelve hours after administration mice were sacrificed and blood, tumor and liver tissue were harvested. Blood samples were analyzed to determine liver, kidney and bone marrow function, tissues were used for transcriptome analyses. Key results: The AL irinotecan group showed worsened organ function and decreased leukocyte numbers. These effects were abated in PBF animals. PBF led to an altered transcriptional response in the liver of irinotecan-treated mice, including decreased cellular injury and increased stress resistance. Hepatic metabolism of irinotecan was also significantly changed due to PBF. The transcriptional response of tumor tissue observed after PBF was hardly affected compared to AL fed animals. Conclusions: Transcriptional changes after PBF to irinotecan treatment showed an improved protective stress response in healthy liver but not in tumor tissue, including changes in irinotecan metabolism. These data help to unravel the mechanisms underlying the effects of fasting on irinotecan and help to improve outcome of chemotherapeutic treatment in cancer patients