High-detectivity optical heterodyne method for wideband carrier-envelope phase noise analysis of laser oscillators.

Broadband characterization of the carrier-envelope phase (CEP) noise spectral density of free-running mode-locked lasers is essential for advanced low-noise optical frequency comb designs. Here we present a direct method that utilizes an optical heterodyne beat between a pair of repetition-rate-locked mode-locked lasers for CEP noise characterization, without requiring an f-2f interferometer or nonlinear optical conversion steps. A proof-of-principle experiment in a femtosecond Yb-fiber laser achieves CEP noise spectral density characterization with >270 dB dynamic range over a Fourier frequency range from 5 mHz to 8 MHz. The measurement noise floor is well below 1 µrad/√Hz, enabling dependable detection down to a quantum-limited noise floor. The method can resolve various noise mechanisms that cause specific CEP noise spectral shapes. The underlying mechanisms are further analyzed in terms of spurious temporal correlation to distinguish between technical and stochastic noise signatures. Moreover, a Hadamard deviation analysis reveals a varying degree of frequency stability in the measured CEP time series.

Excess carrier-envelope phase noise generation in saturable absorbers.

Attosecond spectroscopy and precision frequency metrology depend on the stabilization of the carrier-envelope phase (CEP) of mode-locked lasers. Unfortunately, the phase of only a few types of lasers can be stabilized to jitters in the few-hundred millirad range. In a comparative experimental study, we analyze a femtosecond Ti:sapphire laser and three mode-locked fiber lasers. We numerically demodulate recorded time series of the free-running carrier-envelope beat note. Our analysis indicates a correlation between amplitude and frequency fluctuations at low Fourier frequencies for essentially all lasers investigated. While this correlation typically rolls off at frequencies beyond 100 kHz, we see clear indications for a broadband coupling mechanism in one of the fiber lasers. We suspect that the observed coupling mechanism acts to transfer intracavity power fluctuations into excess phase noise. This coupling mechanism is related to the mode-locking mechanism employed and not to the gain medium itself. We further verify this hypothesis by numerical simulations, which identify resonances of the saturable absorber mirror as a possible explanation for the coupling mechanism. Finally, we discuss how to avoid a detrimental influence of such resonances.

Role of Intrapulse Coherence in Carrier-Envelope Phase Stabilization.

The concept of coherence is of fundamental importance for describing the physical characteristics of light and for evaluating the suitability for experimental application. In the case of pulsed laser sources, the pulse-to-pulse coherence is usually considered for a judgment of the compressibility of the pulse train. This type of coherence is often lost during propagation through a highly nonlinear medium, and pulses prove incompressible despite multioctave spectral coverage. Notwithstanding the apparent loss of interpulse coherence, however, supercontinua enable applications in precision frequency metrology that rely on coherence between different spectral components within a laser pulse. To judge the suitability of a light source for the latter application, we define an alternative criterion, which we term intrapulse coherence. This definition plays a limiting role in the carrier-envelope phase measurement and stabilization of ultrashort pulses. It is shown by numerical simulation and further corroborated by experimental data that filamentation-based supercontinuum generation may lead to a loss of intrapulse coherence despite near-perfect compressibility of the pulse train. This loss of coherence may severely limit active and passive carrier-envelope phase stabilization schemes and applications in optical high-field physics.

Intracavity measurement of the electro-optic Kerr effect via carrier-envelope phase demodulation.

Placing a sinusoidally driven air capacitor in the intracavity beam path of a mode-locked few-cycle Ti:sapphire oscillator, we measure the influence of the electro-optical Kerr effect on the carrier-envelope phase of the laser pulses. Using a capacitor length of only 8 cm at atmospheric pressure, we observe a Kerr-induced frequency modulation of the carrier-envelope beat note. From the measured frequency excursion, we determine a Kerr constant of the order of 10-27 m2/V2, which is found to agree with theoretically computed hyperpolarizabilities of the nitrogen and oxygen molecules. The carrier-envelope phase only depends on the dispersion of the hyperpolarizability, which has been previously found very challenging to measure in the gas phase. Our substantially more sensitive measurement method for the electro-optic Kerr effect in air may prove a valuable tool for non-contact measurements of high voltages in power grids and even for monitoring atmospheric electric fields during thunderstorms.

Low-dose-rate brachytherapy for low-grade prostate cancer.

BACKGROUND: Prostate cancer is a radiosensitive type of cancer for which radiotherapy is used for both curative and palliative purposes. Low-dose-rate brachytherapy is an internal radiotherapy technique which allows high doses of radiation to be delivered to a tumour at short range and with a high degree of precision. We have conducted a systematic review of the evidence base for this treatment. The method is not established in Norway. METHOD: This review is based on systematic review articles and publications on treatment, outcomes, adverse effects and health economics considerations found by searching the databases Cochrane Library, Current Controlled Trials, Medline, Embase and NICE (National Institute of Clinical Excellence). RESULTS: Subsequent to long-term observations of the efficacy, adverse effects and costs presented in 43 selected studies, including one randomised, controlled trial, there is still uncertainty as to which of the three methods low-dose brachytherapy, external radiotherapy and radical prostatectomy is optimal. The reason for this is the methodological differences in patient selection and in endpoints such as biochemical disease-free interval and cause-specific survival. The evidence base appears to suggest that low-dose-rate brachytherapy causes more frequent grade 2 and 3 doctor-reported urogenital adverse effects than prostatectomy, but better patient-reported sexual functions and fewer patients with urinary incontinence than after surgery. Low-dose-rate brachytherapy appears to be socioeconomically cost-effective. INTERPRETATION: The evidence base with respect to therapeutic effect and toxicity in men with low-risk prostate cancer treated with low-dose brachytherapy is regarded as solidly documented. However, there are no good prospective randomised multi-centre trials with overall survival as an endpoint.

[High dose rate brachytherapy in prostate cancer in Norway]. / Høydoserate brakyterapi ved prostatakreft i Norge.

BACKGROUND: A correlation exists between applied dose to the prostate and local tumour control. External radiotherapy of the prostate implies administering curative doses near the upper limit of normal tissue tolerance. Brachytherapy with a high dose rate permits an escalation of dose within the prostate without increasing the risk of side effects to the surrounding rectum and bladder. This article presents a study of the first 100 patients in Norway with localized/locally advanced prostate cancer treated with high dose-rate brachytherapy combined with external radiotherapy. MATERIAL AND METHODS: Patients belonging to an intermediate or high risk group and patients in whom radiotherapy was expected to give rise to increased toxicity (irrespective of the clinical stage) were included. Several hollow steel needles were implanted through the perineum into the gland during general anaesthesia. A small Iridium source with a short irradiation length was introduced stepwise and temporarily into each steel needle, according to a meticulate dosing plan. All patients came to an outpatient control 3-5 months after the combined treatment. RESULTS AND INTERPRETATION: Median follow-up was 8 months. Acute side effects were scarce and few complications from the rectum were seen. The observation time was too short to evaluate the relapse-free survival. High dose rate brachytherapy is indicated in patients with prostate cancer of an intermediate or high risk or if a radiation dose with a full external beam proposes a hazard to the patient. Combined radiotherapy (external beam and high dose rate brachytherapy) is considered to be a standard treatment at the Norwegian Radium Hospital.

[Evaluation of family doctor-centred health care in Germany based on AOK Rheinland/Hamburg claims data]. / Evaluation der hausarztzentrierten Versorgung in Deutschland anhand von GKV-Routinedaten der AOK Rheinland/Hamburg.

BACKGROUND: Health insurance funds in Germany are obliged to offer family doctor-centred health care models (Hausarztzentrierte Versorgung, "HzV"). The participation is voluntary for the insured persons. Participants agree to utilise outpatient specialist care only if their family doctor or general practitioner ("gatekeeper") refers them to a specialist. The aim of this programme is to both strengthen the role of general practitioners and to avoid unnecessary specialist visits and double examinations. Moreover, the quality of care should increase and costs decrease. There is a controversial debate among health politicians whether these objectives can be achieved with current HzV contracts. Therefore, the aim of this project was to conduct an economic evaluation of family doctor-centred health care compared with the standard of care. METHODS: The analysis covered continuously insured adult HzV participants, who have been enrolled in the contract offered by a large German sickness fund (AOK Rheinland/Hamburg) since 2011. In addition, the analysis contained data of a control group which was three times larger than the intervention group. Logistic regression analysis with relevant characteristics (social demographics, health care utilisation, cost, and Charlson Comorbidity Index) of participants and non-participants was conducted to assess the likelihood of participation in the HzV contract. With the subsequent propensity score matching, differences in the characteristics between the control and the intervention group were compensated for the base year 2010 in order to be able to evaluate the influence of the HzV contract in subsequent years. Study objectives were to analyse differences in costs as well as utilisation of services between HzV participants and the control group. RESULTS: The intervention group consisted of 25,201 HzV participants with an average age of 49.5 years [SD: 17.9]. 54.4% of them were female. The HzV participants showed significantly higher costs compared to the control group in the first and in the second year after enrolment. Drug costs in the first year added up to an average of 499 EUR [SD: 2,021] compared to 477 EUR [SD: 2,050] in the control group. In the second year, the drug costs were 544 EUR [SD: 2,758] in the intervention group and 522 EUR [SD: 2,341] in the control group. In addition, the analysis showed a higher number of specialist referrals issued by general practitioners in the intervention group. However, the length of stay in hospitals was shown to be decreasing for HzV participants. DISCUSSION: The higher costs and use of services indicate a higher morbidity (Charlson Comorbidity Index and in comparison to the German population) of HzV participants. The cost level increases in both groups, but within the group of HzV participants, the relative cost increase in the second year was lower than in the control group. The results of this study demonstrate that family doctor-centred health care is assumed to be more efficient in the long term. With regard to the objective of these contracts, quality improvement may not be achievable at the same time as cost savings. As our data set cannot distinguish between changes of patient behaviour and physician behaviour, the results of our study need to be interpreted with caution.

[Treatment of hormone-resistant prostate cancer]. / Behandling av hormonresistent prostatakreft.

Hormone-resistant prostate cancer is defined by disease progression despite of castration levels of serum testosterone. Due to a good palliative effect and low toxicity, radiotherapy is the cornerstone in treatment of painful bone metastases, the most frequent symptom of advanced hormone-resistant prostate cancer. Patients presenting with spinal cord compression should be assessed for decompressive surgery before radiotherapy. With local growth of prostate cancer and problems with urination, a transurethral resection may palliate symptoms. Postoperative radiotherapy should however be considered for these patients, so local regrowth of the tumour can be prevented. Taxan-based chemotherapy (docetaxel) is the first treatment shown to increase overall survival in patients with hormone-resistant prostate cancer, and is today's standard treatment of Norwegian patients (guidelines from the Norwegian Urological Cancer Group). Secondary hormone treatment and administration of bisphosphonates are other established alternatives for palliation of symptoms in patients with hormone-resistant prostate cancer. The survival of future patients with such cancer is expected to improve if multidisciplinary health care teams with knowledge of prostate cancer tumour biology administer new treatments.

Implementation of high-dose-rate brachytherapy and androgen deprivation in patients with prostate cancer.

PURPOSE: To evaluate outcome (overall survival [OS], the actuarial 5-year cancer-specific survival [CSS], disease-free survival [DFS], biochemical failure-free survival [BFS]), complications and morbidity in patients treated with high-dose-rate brachytherapy (HDR-BT) boost and hormonal treatment with curative aims. METHODS: Between 2004 and 2009, 275 prospectively followed pN0/N0M0 patients were included: 19 patients (7%) with T2, Gleason score 7 and prostate-specific antigen (PSA) <10 and 256 patients (93%) with T3 or Gleason score 8-10 or PSA >20 received multimodal treatment with conformal four-field radiotherapy (prostate/vesiculae 2 Gy × 25) combined with HDR-BT (iridium 192; prostate 10 Gy × 2) with long-term androgen deprivation therapy (ADT). RESULTS: After a median observation time of 44.2 months (range, 10.4-90.5 months) 12 patients had relapsed clinically and/or biochemically and 10 patients were dead, of which 2 patients died from prostate cancer. Five-year estimates of BFS, CSS, DFS, and OS rates were 98.5%, 99.3%, 95.6%, and 96.3%, respectively. None of the patients with either Gleason score <8 or with intermediate risk profile had relapsed. The number of HDR-BT treatments was not related to outcome. Despite of age (median, 65.7 years; range, 45.7-77 years) and considerable pretreatment comorbidity in 39 of 275 patients, Genitourinary treatment-related morbidity was moderate with long-lasting Radiation Therapy Oncology Group Grade 2 voiding problems in 26 patients (9.5%) and occasionally mucous discharge in 20 patients (7%), none with Grade >2 for gastrointestinal at follow-up. Complications during implantations were related to pubic arch interference (4 patients) and lithotomy time, causing 2 patients to develop compartment syndrome. CONCLUSION: Despite still preliminary observations, our 5-year outcome estimates favor the implementation of high-dose-rate brachytherapy in high-risk patients combined with conformal external radiotherapy and long-term ADT. High-quality implants can be achieved by a trained specialized team at a high-turnover center using transrectal ultrasound-based treatment plans with acceptable morbidity and complication rates.

[Deep vein thrombosis and localized rhabdomyolysis in a patient with bladder cancer]. / Dyp venetrombose og lokalisert rhabdomyolyse hos en pasient med blaerekreft.

BACKGROUND: Rhabdomyolysis is caused by skeletal muscle injury that results in the release of intracellular contents into the circulatory system. In certain cases, potentially fatal conditions may develop. Multiple conditions followed by muscular necrosis may lead to rhabdomyolysis. MATERIAL AND METHODS: We present a case history of a patient with bladder cancer in whom deep vein thrombosis was complicated by rhabdomyolysis. The patient developed acute renal failure. We have also searched the literature for similar cases. RESULTS AND INTERPRETATION: The patient did not respond to the treatment given. In order to save his life, the affected extremity was amputated. Rhabdomyolysis is a very rare complication of deep vein thrombosis. There are only a few patients described in the literature in which these conditions occur simultaneously. The diagnosis of rhabdomyolysis can easily be missed, as the two conditions give almost identical symptoms.