Suppression of black-hole growth by strong outflows at redshifts 5.8-6.6.

Bright quasars, powered by accretion onto billion-solar-mass black holes, already existed at the epoch of reionization, when the Universe was 0.5-1 billion years old1. How these black holes formed in such a short time is the subject of debate, particularly as they lie above the correlation between black-hole mass and galaxy dynamical mass2,3 in the local Universe. What slowed down black-hole growth, leading towards the symbiotic growth observed in the local Universe, and when this process started, has hitherto not been known, although black-hole feedback is a likely driver4. Here we report optical and near-infrared observations of a sample of quasars at redshifts 5.8 ≲ z ≲ 6.6. About half of the quasar spectra reveal broad, blueshifted absorption line troughs, tracing black-hole-driven winds with extreme outflow velocities, up to 17% of the speed of light. The fraction of quasars with such outflow winds at z ≳ 5.8 is ≈2.4 times higher than at z ≈ 2-4. We infer that outflows at z ≳ 5.8 inject large amounts of energy into the interstellar medium and suppress nuclear gas accretion, slowing down black-hole growth. The outflow phase may then mark the beginning of substantial black-hole feedback. The red optical colours of outflow quasars at z ≳ 5.8 indeed suggest that these systems are dusty and may be caught during an initial quenching phase of obscured accretion5.

Preliminary results of a cohort study of induction chemotherapy-based treatment for locally recurrent rectal cancer.

BACKGROUND: A significant number of patients treated for locally recurrent rectal cancer have local or systemic failure, especially after incomplete surgical resection. Neoadjuvant treatment regimens in patients who have already undergone preoperative (chemo)radiotherapy for the primary tumour are limited. The objective of the present study was to evaluate the influence of a neoadjuvant regimen incorporating induction chemotherapy (ICT) in patients with locally recurrent rectal cancer who had preoperative (chemo)radiotherapy for the primary cancer or an earlier local recurrence. METHODS: Patients were treated with a sequential neoadjuvant regimen including three or four cycles of 5-fluorouracil and oxaliplatin-containing chemotherapy. When no progressive disease was found at evaluation, neoadjuvant treatment was continued with chemoradiation therapy (CRRT) using 30 Gy with concomitant capecitabine. If there was a response to ICT, the patient was advised to continue with systemic chemotherapy after CRRT as consolidation chemotherapy while waiting for resection. These patients were compared with patients who received CRRT alone in the same time interval. RESULTS: Of 58 patients who had ICT, 32 (55 per cent) had surgery with clear resection margins, of whom ten (17 per cent) exhibited a pathological complete response (pCR). The remaining 26 patients had 23 R1 and three R2 resections. In 71 patients who received CRRT, a similar rate of R0 (35 patients) and R1 (36) resection was found (P = 0·506), but only three patients (4 per cent) had a pCR (P = 0·015). CONCLUSION: The incorporation of ICT in neoadjuvant regimens for locally recurrent rectal cancer is a promising strategy.

Results of a pooled analysis of IOERT containing multimodality treatment for locally recurrent rectal cancer: Results of 565 patients of two major treatment centres.

OBJECTIVE: Aim of this study is analysing the pooled results of Intra-Operative Electron beam Radiotherapy (IOERT) containing multimodality treatment of locally recurrent rectal cancer (LRRC) of two major treatment centres. METHODS AND MATERIALS: Five hundred sixty five patients with LRRC who underwent multimodality-treatment up to 2010 were studied. The preferred treatment was preoperative chemo-radiotherapy, surgery and IOERT. In uni- and multivariate analyses risk factors for local re-recurrence, distant metastasis free survival, relapse free survival, cancer-specific survival and overall survival were studied. RESULTS: Two hundred fifty one patients (44%) underwent a radical (R0) resection. In patients who had no preoperative treatment the R0 resection rate was 26%, and this was 43% and 50% for patients who respectively received preoperative re-(chemo)-irradiation or full-course radiotherapy (p < 0.0001). After uni- and multivariate analysis it was found that all oncologic parameters were influenced by preoperative treatment and radicality of the resection. Patients who were re-irradiated had a similar outcome compared to patients, who were radiotherapy naive and could undergo full-course treatment, except the chance of local re-recurrence was higher for re-irradiated patients. Waiting-time between preoperative radiotherapy and IOERT was inversely correlated with the chance of local re-recurrence, and positively correlated with the chance of a R0 resection. CONCLUSIONS: R0 resection is the most important factor influencing oncologic parameters in treatment of LRRC. Preoperative (chemo)-radiotherapy increases the chance of achieving radical resections and improves oncologic outcomes. Short waiting-times between preoperative treatment and IOERT improves the effectiveness of IOERT to reduce the chance of a local re-recurrence.

Optomechanical coupling between a multilayer graphene mechanical resonator and a superconducting microwave cavity.

The combination of low mass density, high frequency and high quality factor, Q, of mechanical resonators made of two-dimensional crystals such as graphene make them attractive for applications in force/mass sensing and exploring the quantum regime of mechanical motion. Microwave optomechanics with superconducting cavities offers exquisite position sensitivity and enables the preparation and detection of mechanical systems in the quantum ground state. Here, we demonstrate coupling between a multilayer graphene resonator with quality factors up to 220,000 and a high-Q superconducting cavity. Using thermomechanical noise as calibration, we achieve a displacement sensitivity of 17 fm Hz(-1/2). Optomechanical coupling is demonstrated by optomechanically induced reflection and absorption of microwave photons. We observe 17 dB of mechanical microwave amplification and signatures of strong optomechanical backaction. We quantitatively extract the cooperativity C, a characterization of coupling strength, from the measurement with no free parameters and find C = 8, which is promising for the quantum regime of graphene motion.

Feasibility of reirradiation in the treatment of locally recurrent rectal cancer.

BACKGROUND: Many patients with locally recurrent rectal cancer receive radiotherapy for the treatment of the primary tumour. It is unclear whether reirradiation is safe and effective when a local recurrence develops. The aim of this study was to evaluate the toxicity and oncological outcome of reirradiation in patients with locally recurrent rectal carcinoma. METHODS: From March 1994 until December 2013, data on patients with locally recurrent rectal cancer (without distant metastasis) were entered into a database. Patients were reirradiated with a reduced dose of 30 Gy and received an intraoperative electron radiotherapy boost during surgery. Morbidity associated with radiotherapy, postoperative complications and oncological outcome were evaluated. RESULTS: Clear margins (R0) were obtained in 75 (55·6 per cent) of the 135 patients who were reirradiated. Forty-six patients developed serious postoperative complications and the 30-day mortality rate was 4·6 per cent. Multivariable analysis showed that margin status was the main factor influencing oncological outcome (hazard ratio for overall survival 2·51 for R1 and 3·19 for R2 versus R0 resection; both P < 0·001). There was no significant difference in survival between the reirradiated group and a group of 113 patients who had full-course irradiation (5-year overall survival rate 34·1 and 39·1 per cent respectively; P = 0·278). Both reirradiation and full-course irradiation were associated with better survival than no irradiation in a historical control group of 24 patients (5-year overall survival rate 23 per cent; P = 0·225 and P = 0·062). CONCLUSION: Reirradiation (with concomitant chemotherapy) has few side-effects and complements radical resection of recurrent rectal cancer.

Abdominosacral resection: long-term outcome in 86 patients with locally advanced or locally recurrent rectal cancer.

AIMS: The purpose of this study is to evaluate the outcome of abdominosacral resections (ASR) in patients with locally advanced or recurrent rectal cancer. METHODS: From 1994 until 2012 patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) underwent a curative ASR and were enrolled in a database. The postoperative complication rates, predictive factors on oncological outcome and survival rates were registered. RESULTS: Seventy-two patients with LRRC (mean age 63; 44 male, 28 female) and 14 patients with LARC (mean age 65; 6 male, 8 female) underwent ASR. R0 resection was achieved in 37 patients with LRRC and 11 patients with LARC. Twenty-seven patients underwent an R1 resection (3 in the LARC group). Eight patients had an R2 resection, compared to no patients in the LARC group. In respectively 26 and 1 patients of the LRRC and LARC groups a grade 3 or 4 complication occurred and the 30-days mortality rate was respectively 3% and 7%. The 5-years overall survival was 28% and 24% respectively. CONCLUSION: En bloc radical resection remains the primary goal in the treatment of dorsally located (recurrent) rectal cancer. After thorough patient selection, ASR is a safe procedure to perform, shows acceptable morbidity rates and leads to a good oncological outcome.

Development of mammalian embryos exposed to mixed-size nanoparticles.

Inhaled or ingested ultrafine nanoparticles and their effects on early pregnancy remain polemic. The objectives of the study were: (a) to determine the embryotoxic effects of nanoparticles at the 2-cell stage and (b) to localize the internalized nanoparticles in the blastocyst. Thawed mouse 2-cell embryos (no. = 128) were exposed to either mixed-size polystyrene-based nanoparticles (11 million/ml) or control G1.3 medium and assessed after 72 hours. Additionally, blastocysts (no. = 146) were exposed to nanoparticles and analyzed. The results showed that the nanoparticles did not inhibit 2-cell embryo development to the blastocyst stage (89.4 vs 96.8%; treated vs control). There were no differences in hatching (34.8 vs 43.5%), implantation (13.6 vs 24.2%) and degeneration (10.6 vs 3.2%). Delayed exposure to nanoparticles showed similar percent hatching (40.7 vs 47.3%) and implantation (17.6 vs 20.0%). Although nanoparticles were internalized, embryo development was not inhibited suggesting a lack of embryotoxicity. During hatching, the larger nanoparticles adhered to the extruding blastocyst, preferentially on trophoblasts, but interference was insignificant. Exposure to polystyrene-based nanoparticles at the concentration tested are not associated with embryonic loss.

Ultrastructural alterations in heated canine myocardium.

BACKGROUND AND OBJECTIVE: The anisotropy factor of light scattering (g) (wavelength 632.8 nm) in heated myocardium decreases as a function of temperature, suggesting, on the basis of Mie theory of light scattering, formation of an increasing number of particles with diameters smaller than the incident wavelength. STUDY DESIGN/MATERIALS AND METHODS: To test this hypothesis, fresh myocardium was heated at constant temperatures between 37 degrees C and 75 degrees C for 1,000 s. Changes in size and number of granules generated by disintegrating organelles and sarcomeres were studied as a function of temperature by transmission electron microscopy, planimetry and particle counting. RESULTS: The mitochondria started to disintegrate at 45 degrees C and myofibrils between 45 degrees C and 50 degrees C into increasing numbers of small electron dense granules (diameter 50-200 nm), which correlated with the observed decrease of g from 0.93 +/- 0.02 (at room temperature to 45 degrees C) to 0.77 +/- 0.05 at 75 degrees C. CONCLUSION: The scattering coefficient microseconds of 161 +/- 33 cm-1 did not change significantly.

Colorectal adenomas: inflammatory changes that simulate malignancy after laser coagulation--evaluation with transrectal US.

To evaluate the assumption that inflammatory changes in the rectal wall after treatment of colorectal adenoma with photocoagulation may simulate malignant infiltration, the findings were reviewed in 23 follow-up examinations performed with transrectal ultrasound (TRUS) in 17 patients with benign adenoma. Special attention was given to the appearance of the wall layers underneath the adenoma. After partial coagulation, changes in the colorectal wall were usually seen on TRUS scans obtained early in follow-up; sometimes the thickened muscle layer had an irregular outer margin. In three of the 13 early examinations, lesions mimicked malignancy. To correlate these findings with histologic proof, an experimental study was performed: Colorectal specimens from pigs were examined with ultrasound (US) and microscopy. The abnormal sonographic appearance of specimens on US scans was caused by an inflammatory reaction in the deep wall layers; concomitant serositis appeared to be responsible for the malignancy-mimicking irregular outer margin. In screening for malignancy in colorectal adenoma, TRUS may cause overstaging during the first 6 weeks after polypectomy or after a session of laser treatment and should be avoided.

Changes in the optical properties (at 632.8 nm) of slowly heated myocardium.

The three transport equation optical properties, the absorption coefficient, the scattering coefficient, and the average cosine of the scattering angle, or anisotropy factor have been measured (at 632.8 nm) for canine myocardium after it is heated in a water bath at room temperature and at 37-75 degrees C for 1000 s. The measurement system was a double integrating sphere with collimated light and utilized the adding-doubling solution to the equation of radiative transfer. The absorption coefficient (room temperature control, 2.0 +/- 0.4 cm(-1)) began to increase and the anisotropy factor (room temperature control, 0.93 +/- 0.02) to decrease at above 45 degrees C. At 75 degrees C the changes were significant at the p < 0.0005 level (absorption, 4.5 +/- 1.3 cm(-1); anisotropy, 0.78 +/- 0.05). There was no significant change in the scattering coefficient (room temperature controls, 161 +/- 33 cm(-1)).

Heat-induced structural alterations in myocardium in relation to changing optical properties.

In canine myocardium, organelles fragmented progressively with temperatures, at 45-75 degrees (1000-s exposure). This correlated with a gradual decrease in the anisotropy of scattering.

Effect of percutaneous interstitial thermal laser on normal liver of pigs: sonographic and histopathological correlations.

Tumour necrosis can be induced by interstitial application of low power laser light, which causes thermal damage to the tissue. In normal pig liver the effects were studied of low power Nd:YAG laser light (continuous wave; 1.5 W, 10 min, wavelength 1064 nm), administered percutaneously via a 600 micron fibre. Ultrasound images were compared with histopathological findings. Histopathology showed induction of sharply demarcated lesions with a mean diameter of 10-15 mm (days 0 and 7), consisting of coagulative necrosis. Healing of the lesion occurred by granulation, fibrosis and removal of cell debris. Lesions could not be seen by week 4, which suggests complete regeneration. Ultrasonography showed a good correlation with histopathology, especially at 1 week when different histopathological tissue layers could be discriminated by ultrasonography. It is concluded that thermal lesions in liver can be induced via a percutaneous route and that ultrasound imaging is useful in monitoring the lesions during and after the procedure.

[Non-invasive method of arterial oxygen saturation monitoring in the neonatal intensive care unit (with a review of blood oxygen monitoring methods)]. / Non-invasieve trendbewaking van de arteriële zuurstofsaturatie in de neonatale intensive care (met overzicht van bloedzuurstofbewakings-methoden).

Recently a new method (pulse oximetry) became available, which enables us to monitor non-invasively the arterial oxygen saturation in neonates. We tested this new method in several premature infants, from the time that oxygen therapy was instituted (IPPV; CPAP), in order to evaluate its potential clinical use. In stable patients we found a better correlation (r = 0.90) between the oxygen saturation measured transcutaneously and that measured in an arterial blood sample that the correlation (r = 0.22) between oxygen tensions measured either transcutaneously or in a blood sample. Although transcutaneous monitoring of the arterial oxygen saturation, especially because it is a continuous process, can be a valuable adjunct in monitoring premature infants who receive extra oxygen, it can not replace the necessity for intermittent blood sampling to determine 'arterial blood gases'. One should also remember that; due to the fact that the position of oxyhemoglobin dissociation curve depends on several factors; the SO2 can not simply be derived from the pO2 or vice versa. Continuous transcutaneous monitoring of oxygen saturation may decrease the frequency with which arterial blood samples for blood gas measurement have to be taken.