Hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy: HARP-trial

Contains fulltext : 88436.pdf (publisher's version ) (Open Access)BACKGROUND: Transplantation is the only treatment offering long-term benefit to patients with chronic kidney failure. Live donor nephrectomy is performed on healthy individuals who do not receive direct therapeutic benefit of the procedure themselves. In order to guarantee the donor's safety, it is important to optimise the surgical approach. Recently we demonstrated the benefit of laparoscopic nephrectomy experienced by the donor. However, this method is characterised by higher in hospital costs, longer operating times and it requires a well-trained surgeon. The hand-assisted retroperitoneoscopic technique may be an alternative to a complete laparoscopic, transperitoneal approach. The peritoneum remains intact and the risk of visceral injuries is reduced. Hand-assistance results in a faster procedure and a significantly reduced operating time. The feasibility of this method has been demonstrated recently, but as to date there are no data available advocating the use of one technique above the other. METHODS/DESIGN: The HARP-trial is a multi-centre randomised controlled, single-blind trial. The study compares the hand-assisted retroperitoneoscopic approach with standard laparoscopic donor nephrectomy. The objective is to determine the best approach for live donor nephrectomy to optimise donor's safety and comfort while reducing donation related costs. DISCUSSION: This study will contribute to the evidence on any benefits of hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy. TRIAL REGISTRATION: Dutch Trial Register NTR1433

Designing theoretically-informed implementation interventions

Clinical and health services research is continually producing new findings that may contribute to effective and efficient patient care. However, the transfer of research findings into practice is unpredictable and can be a slow and haphazard process. Ideally, the choice of implementation strategies would be based upon evidence from randomised controlled trials or systematic reviews of a given implementation strategy. Unfortunately, reviews of implementation strategies consistently report effectiveness some, but not all of the time; possible causes of this variation are seldom reported or measured by the investigators in the original studies. Thus, any attempts to extrapolate from study settings to the real world are hampered by a lack of understanding of the effects of key elements of individuals, interventions, and the settings in which they were trialled. The explicit use of theory offers a way of addressing these issues and has a number of advantages, such as providing: a generalisable framework within which to represent the dimensions that implementation studies address, a process by which to inform the development and delivery of interventions, a guide when evaluating, and a way to allow for an exploration of potential causal mechanisms. However, the use of theory in designing implementation interventions is methodologically challenging for a number of reasons, including choosing between theories and faithfully translating theoretical constructs into interventions. The explicit use of theory offers potential advantages in terms of facilitating a better understanding of the generalisability and replicability of implementation interventions. However, this is a relatively unexplored methodological area

Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell carcinoma: Long-term results of a randomized controlled trial

Background: This is a randomized, controlled trial of preoperative chemotherapy in patients undergoing surgery for oesophageal squamous cell carcinoma (OSCC). Patients were allocated to chemotherapy, consisting of 2-4 cycles of cisplatin and etoposide, followed by surgery (CS group) or surgery alone (S group). Initial results reported only in abstract form in 1997, demonstrated an advantage for overall survival in the CS group. The results of this trial have been updated and discussed in the timeframe in which this study was performed.Methods: This trial recruited 169 patients with OSCC, 85 patients assigned to preoperative chemotherapy and 84 patients underwent immediate surgery. The primary study endpoint was overall survival (OS), secondary endpoints were disease free survival (DFS) and pattern of failure. Survival has been determined from Kaplan-Meier curves and treatment comparisons made with the log-rank test.Results: There were 148 deaths, 71 in the CS and 77 in the S group. Median OS time was 16 months in the CS group compared with 12 months in the S group; 2-year survival rates were 42% and 30%; and 5-year survival rates were 26% and 17%, respectively. Intention to treat analysis showed a significant overall survival benefit for patients in the CS group (P = 0.03, by the log-rank test; hazard ratio [HR] 0.71; 95%CI 0.51-0.98). DFS (from landmark time of 6 months after date of randomisation) was also better in the CS-group than in the S group (P = 0.02, by the log-rank test; HR 0.72; 95%CI 0.52-1.0). No difference in failure pattern was observed between both treatment arms.Conclusions: Preoperative chemotherapy with a combination of etoposide and cisplatin significantly improved overall survival in patients with OSCC

Phase II study of bi-weekly administration of paclitaxel and cisplatin in patients with advanced oesophageal cancer

In a phase I study we demonstrated the feasibility of a bi-weekly combination of paclitaxel 180 mg m−2 with cisplatin 60 mg m−2. In this study we further assessed toxicity and efficacy of this schedule in the treatment of advanced cancer of the oesophagus or the gastro-oesophageal junction. Patients received paclitaxel 180 mg m−2 administered over 3 h followed by a 3-h infusion of cisplatin 60 mg m−2. Patients were retreated every 2 weeks unless granulocytes were <0.75×109 or platelets <75×109. Patients were evaluated after three and six cycles and responding patients received a maximum of eight cycles. Fifty-one patients were enrolled into the study. The median age was 56 years (range 32–78). WHO performance status were: 0 (19 patients); 1 (29 patients); 2 (three patients). All patients received at least three cycles of chemotherapy and all were evaluable for toxicity and response. Haematological toxicity consisted of uncomplicated neutropenia grade 3 in 39% and grade 4 in 31% of patients. Five patients (10%) were hospitalised, three patients because of treatment related complications and two patients because of infections without neutropenia. Sensory neurotoxicity was the predominant non-haematological toxicity; grade 1 and 2 neurotoxicity was observed in 43 and 20% of patients, respectively. Response evaluation in 51 patients with measurable disease: complete response 4%, partial response 39%, stable disease 43% and progressive disease in 14% of the patients. The median duration of response was 8 months. The median survival for all patients was 9 (range 2–29+) months and the one-year survival rate was 43%. Four patients who received additional local treatment (two patients surgery and two patients radiotherapy) are still disease free after a follow-up of 20–29 months. This bi-weekly treatment of paclitaxel and cisplatin is well tolerated by patients with advanced oesophageal cancer. The toxicity profile of this regimen compares favourable to that of previously used cisplatin- and paclitaxel-based regimens. Trials are underway evaluating this bi-weekly regimen in a neo-adjuvant setting

Integrated photonic quantum gates for polarization qubits

Integrated photonic circuits have a strong potential to perform quantum information processing. Indeed, the ability to manipulate quantum states of light by integrated devices may open new perspectives both for fundamental tests of quantum mechanics and for novel technological applications. However, the technology for handling polarization encoded qubits, the most commonly adopted approach, is still missing in quantum optical circuits. Here we demonstrate the first integrated photonic Controlled-NOT (CNOT) gate for polarization encoded qubits. This result has been enabled by the integration, based on femtosecond laser waveguide writing, of partially polarizing beam splitters on a glass chip. We characterize the logical truth table of the quantum gate demonstrating its high fidelity to the expected one. In addition, we show the ability of this gate to transform separable states into entangled ones and vice versa. Finally, the full accessibility of our device is exploited to carry out a complete characterization of the CNOT gate through a quantum process tomography.Comment: 6 pages, 4 figure

First-line treatment with oxaliplatin and capecitabine in patients with advanced or metastatic oesophageal cancer: a phase II study

This phase II study assessed the safety and efficacy of oxaliplatin and capecitabine in patients with advanced oesophageal cancer. Fifty-one eligible patients received oxaliplatin 130 mg m−2 intravenously on day 1 and capecitabine 1000 mg m−2 orally twice daily on days 1 to 14 in a 21-day treatment cycle as first-line treatment for advanced oesophageal cancer. Grade 3 neutropenia was seen in one patient and anaemia in another patient. No grade 4 haematological toxicities were observed. Grade 4 non-haematological toxicity (lethargy) occurred in one patient (2%). Grade 3 non-haematological toxicity was seen in 14 (27%) patients (vomiting and polyneuropathy (8%); nausea (6%); lethargy and hand–foot syndrome (4%); and anorexia, diarrhoea, and hyperbilirubinaemia (each in one patient)). In 22% of the patients, toxicity was the reason for stopping the treatment. The overall response rate was 39%. The median overall survival was 8 months; the 1-year survival rate was 26%. In the quality of life (QoL) analysis, the emotional well-being improved during treatment, but the physical functioning scores declined. The fatigue score on the symptom scales increased. Overall, the global QoL score did not change during treatment. In conclusion, the activity of oxaliplatin and capecitabine is comparable with other chemotherapy regimens in advanced oesophageal cancer with a low frequency of grade 3/4 toxicity. Because this treatment can be given on an outpatient basis, it is probably less toxic than cisplatin-based therapy and preserves QoL during treatment, it is a viable treatment option in patients with advanced oesophageal cancer

Distracting the Mind Improves Performance: An ERP Study

When a second target (T2) is presented in close succession of a first target (T1), people often fail to identify T2, a phenomenon known as the attentional blink (AB). However, the AB can be reduced substantially when participants are distracted during the task, for instance by a concurrent task, without a cost for T1 performance. The goal of the current study was to investigate the electrophysiological correlates of this paradoxical effect.Participants successively performed three tasks, while EEG was recorded. The first task (standard AB) consisted of identifying two target letters in a sequential stream of distractor digits. The second task (grey dots task) was similar to the first task with the addition of an irrelevant grey dot moving in the periphery, concurrent with the central stimulus stream. The third task (red dot task) was similar to the second task, except that detection of an occasional brief color change in the moving grey dot was required. AB magnitude in the latter task was significantly smaller, whereas behavioral performance in the standard and grey dots tasks did not differ. Using mixed effects models, electrophysiological activity was compared during trials in the grey dots and red dot tasks that differed in task instruction but not in perceptual input. In the red dot task, both target-related parietal brain activity associated with working memory updating (P3) as well as distractor-related occipital activity was significantly reduced.The results support the idea that the AB might (at least partly) arise from an overinvestment of attentional resources or an overexertion of attentional control, which is reduced when a distracting secondary task is carried out. The present findings bring us a step closer in understanding why and how an AB occurs, and how these temporal restrictions in selective attention can be overcome

Few-body resonances in light nuclei

We have localized several few-body resonances in light nuclei, using methods which can properly handle two- or three-body resonant states. Among other results, we predict the existence of a three-neutron resonance, small spin-orbit splittings between the low-lying states in He-5 and Li-5, the nonexistence of the soft dipole resonance in He-6, new 1+ states in Li-8 and B-8, and the presence of a nonlinear amplification phenomenon in the 0+_2 state of C-12

Is Mn-Bound Substrate Water Protonated in the S2 State of Photosystem II?

In spite of great progress in resolving the geometric structure of the water-splitting Mn4OxCa cluster in photosystem II, the binding sites and modes of the two substrate water molecules are still insufficiently characterized. While time-resolved membrane-inlet mass spectrometry measurements indicate that both substrate water molecules are bound to the oxygen-evolving complex (OEC) in the S2 and S3 states (Hendry and Wydrzynski in Biochemistry 41:13328–13334, 2002), it is not known (1) if they are both Mn-bound, (2) if they are terminal or bridging ligands, and (3) in what protonation state they are bound in the different oxidation states Si (i = 0, 1, 2, 3, 4) of the OEC. By employing 17O hyperfine sublevel correlation (HYSCORE) spectroscopy we recently demonstrated that in the S2 state there is only one (type of) Mn-bound oxygen that is water exchangeable. We therefore tentatively identified this oxygen as one substrate ‘water’ molecule, and on the basis of the finding that it has a hyperfine interaction of about 10 MHz with the electron spin of the Mn4OxCa cluster, we suggest that it is bound as a Mn–O–Mn bridge within a bis-μ2 oxo-bridged unit (Su et al. in J Am Chem Soc 130:786–787, 2008). Employing pulse electron paramagnetic resonance, 1H/2H Mims electron-nuclear double resonance and 2H-HYSCORE spectroscopies together with 1H/2H-exchange here, we test this hypothesis by probing the protonation state of this exchangeable oxygen. We conclude that this oxygen is fully deprotonated. This result is discussed in the light of earlier reports in the literature