Mid-infrared supercontinuum generation in suspended core tellurite microstructured optical fibers.

We report the fabrication of a tellurite optical fiber with a suspended core design, formed on a 220-nm-wide filament of glass. The fiber was pumped at two different wavelengths (1500 and 2400 nm) using femtosecond pulses generated from an optical parametric oscillator (OPO) in order to produce mid-infrared supercontinuum (SC). We observed that SC spectra extending to 3 µm were readily generated. To further optimize the design, detailed numerical study was performed, which revealed how the fiber structural characteristics dramatically influence the spectral broadening because of the changes in the dispersion profile and in turn, the interplay of nonlinear effects that give rise to SC generation. We found that an accurate control of the core shape can be employed to contain the generated SC spectra within well-defined spectral regions or to provide a broad extension of the continuum to beyond 4 µm.

Four-wave mixing and octave-spanning supercontinuum generation in a small core hydrogenated amorphous silicon fiber pumped in the mid-infrared.

An octave-spanning supercontinuum is generated in a hydrogenated amorphous silicon core fiber when pumped in the mid-infrared regime. The broadband wavelength conversion which extends from the edge of the telecommunications band into the mid-infrared (1.64-3.37 µm) is generated by four-wave mixing (FWM) and subsequent pulse break-up, facilitated by the high material nonlinear figure of merit and the anomalous dispersion of the relatively small 1.7 µm diameter core fiber. The FWM sidebands and corresponding supercontinuum can be tuned through the pump parameters, and show good agreement with the predicted phase-matching curves for the fiber.

Mid-infrared ZBLAN fiber supercontinuum source using picosecond diode-pumping at 2 µm.

We present the first demonstration of mid-IR supercontinuum generation directly pumped with picosecond pulses from a Thulium fiber-amplified gain-switched laser diode at 2 µm. We achieve more than two octaves of bandwidth from 750 - 4000 nm in step-index ZBLAN fiber with Watt-level average power and spectral flatness of less than 1.5 dB over a 1300 nm range in the mid-IR from 2450 - 3750 nm. The system offers high stability, power-scaling capability to the 10 W regime, and demonstrates an attractive route towards relatively inexpensive, versatile and practical sources of high power broadband mid-IR radiation.

Clinical and immunohistochemical assessment of vulval intraepithelial neoplasia following photodynamic therapy using a novel bioadhesive patch-type system loaded with 5-aminolevulinic acid.

BACKGROUND: The work in this study appraised photodynamic treatment (PDT) as a treatment method for vulval intraepithelial neoplasia (VIN) using a novel bioadhesive patch to deliver aminolevulinic acid. An analysis of changes in expression of apoptotic and cell cycle proteins (p53, p21, Mdm2, Blc-2, Bax, Ki-67) in response to PDT was evaluated. METHODS: PDT was performed using non-laser light, either as a one or two-cycle treatment, with clinical and pathological assessment following after 6 weeks. Twenty-three patients with 25 VIN lesions underwent 49 cycles of PDT. Patches were designed to conform to uneven vulval skin and contained 38 mg cm(-2) aminolevulinic acid. Assessment was carried out at 6 weeks post-treatment. Patient-based treatment assessment, along with clinical and pathological changes, were monitored. Immunohistochemical staining was used to elucidate a possible biomolecular basis for induced cellular changes. RESULTS: Most patients (52%) reported a symptomatic response, with normal pathology restored in 38% of lesions. The patch was easy to apply and remove, causing minimal discomfort. Fluorescence inspection confirmed protoporphyrin accumulation. Pain during implementation of PDT was problematic, necessitating some form of local analgesia. Changes in expression of cell cycle and apoptotic-related proteins suggested involvement of apoptotic pathways. Down regulation of p21 and inverse changes in Bcl-2 and Bax were key findings. CONCLUSION: Treatment of VIN lesions using a novel bioadhesive patch induced changes in cell cycle and apoptotic proteins in response to PDT with possible utilisation of apoptotic pathways. The efficacy of PDT in treating VIN could be improved by a better understanding of these apoptotic mechanisms, the influence of factors, such as HPV status, and of the need for effective pain management.

High energy femtosecond fiber chirped pulse amplification system with adaptive phase control.

We demonstrate increased peak power from an Yb fiber CPA system operating with strong self-phase modulation by shaping the spectral-phase of the input pulses. An adaptive control loop used feedback from the output autocorrelation. We investigated pre-compensation of both SPM phase distortion at high energies, and residual dispersion from mismatched stretcher/compressor technologies at low energies. Phase shaping resulted in improved pulse quality. When using a bulk grating stretcher, shaping increased the autocorrelation peak by a factor of 2.9, and with a fiber stretcher, shaping increased the autocorrelation peak by a factor of 3.4. High-quality 800 fs, 65 microJ recompressed pulses were produced. This technique could benefit a wide variety of fiber amplifier systems and is self-optimising for operation at both low and high pulse energies.

An immunohistochemical and morphological analysis of post-chemotherapy ovarian carcinoma.

AIMS: Traditional management of advanced ovarian carcinoma is surgical debulking followed by chemotherapy; however, there is an increasing tendency for neoadjuvant chemotherapy followed by surgery. The morphology of ovarian carcinoma following chemotherapy often differs markedly from native tumour. This study aimed to compare the immunophenotype of post-chemotherapy ovarian carcinomas with that of untreated tumour. METHODS: Post-chemotherapy ovarian carcinomas (n = 16) were stained with a range of antibodies. In six cases, pre-chemotherapy core biopsies were also stained; all were high-grade serous carcinomas. Antibodies used in the study were CK7, CA125, WT1, ER, PR, p53, p16, p63 and MIB1. RESULTS: In eight post-treatment cases, there was minimal or no morphological response to chemotherapy, and in eight there was a significant response (in two additional cases, no residual tumour was identified). All pre-chemotherapy biopsies showed diffuse positivity of the tumour cells with CK7, CA125 and WT1. ER, p53 and p16 were diffusely positive in five, four and three cases respectively. One case was focally PR positive, and all were p63 negative. MIB1 staining was high; all but one case exhibited a proliferation index of >60%. Post-chemotherapy tumours exhibited a similar immunophenotype: diffuse positivity with CK7 in all cases and with CA125, WT1, ER, p53 and p16 in the majority, an immunophenotype in keeping with a serous carcinoma. All were negative with p63, and all but two with PR. The MIB1 proliferation index was lower in those cases exhibiting a significant morphological response, and p53 was less likely to be positive in cases with minimal or no response. CONCLUSIONS: The immunophenotype of post-chemotherapy ovarian carcinomas is very similar to that of native untreated tumours, illustrating that CK7, CA125, WT1, ER, p53 and p16 may be of value in identifying residual tumour cells and in subtyping the neoplasm if a pre-chemotherapy biopsy has not been obtained.

Is laparoscopically assisted radical vaginal hysterectomy for cervical carcinoma safe? A case control study with follow up.

OBJECTIVE: To compare a new surgical approach, laparoscopically assisted radical vaginal hysterectomy (LARVH) with open radical hysterectomy in women with cervical cancer. Can selected women benefit from the minimally invasive approach without compromising safety (recurrence rate) and morbidity (complications)? DESIGN: Retrospective case control study. SETTING: A tertiary referral unit for gynaecological malignancies. POPULATION: Thirty women undergoing LARVH were included and compared with 30 women undergoing open radical surgery. The control group was matched for age, body mass index and disease stage. METHODS: Retrospective collection of data from patient files and follow up. MAIN OUTCOME MEASURES: Recurrence rate, complication rate, hospital stay, nodal counts, blood loss, operating time. RESULTS: Recurrence rates were equal (6.7%). There was one death, in the LARVH group. Follow up was mean 31 months in the LARVH group and 30.9 months in the open group. Blood loss as measured by mean drop in haemoglobin was greater in the open group (2.03 versus 3.01 g/dl, P = 0.02). Transfusions were given in 40% of women in the open group and 16.7% in the LARVH group. Hospital stay was significantly less in the LARVH group (5.9 versus 7.8 nights, P = 0.003). Mean operating time was longer in the LARVH group (131 versus 187 minutes P = 0.0001). Mean nodal counts did not differ significantly (17.4 in open vs 14.8 in LARVH, P > 0.05). There were seven perioperative complications in the open group and four in the LARVH group. There have been two recurrences in each group (6.67%) at mean follow up of 31 (LARVH) and 30.9 (open) months. CONCLUSIONS: The first 30 LARVH procedures performed in this unit are comparable in terms of safety (recurrence rate and complication rate) and economic factors (shorter hospital stay mitigating longer operating time). Further development of this technique is warranted.

Pulse compression at 1.06 microm in dispersion-decreasing holey fibers.

We report compression of low-power femtosecond pulses at 1.06 microm in a dispersion-decreasing holey fiber. Near-adiabatic compression of 130 fs pulses down to 60 fs has been observed. Measured spectra and pulse shapes agree well with numerical simulations. Compression factors of ten are possible in optimized fibers.

the management of vulval intraepithelial neoplasia in Northern Ireland.

In this study, we present the findings of a regional retrospective audit of all cases of vulval intraepithelial neoplasia (VIN) diagnosed in Northern Ireland (NI) over an 11-year period (1989-1999). During the period of the study, there were 97 cases of VIN. Cases of VIN were treated by many different clinicians at 14 hospitals. The commonest symptom at presentation was pruritus vulvae. The most common histopathologic diagnosis was VIN III (73%). In 52% of the cases, there was multifocal VIN, and in 43%, there was involvement of other sites such as the cervix, vagina, or anal region. The most common initial treatment was surgical excision, but a multitude of different treatments were performed initially. During the study period, 18 of 90 patients (20%) for whom follow-up was available developed invasive vulval squamous carcinoma. Most of the vulval cancers were superficially invasive, but three patients died of vulval cancer during the study period. This study illustrates that in NI, VIN is treated at many institutions by a multitude of clinicians. Management seems largely dependent on personal clinician preference and has been haphazard with little central coordination and organized strategy. VIN should be managed by clinicians with expertise in this field and who are treating significant numbers of patients according to evidence-based protocols.

Optimisation of cascaded Yb fiber amplifier chains using numerical-modelling.

We show that it is possible to adapt existing software packages developed originally for modeling telecommunication devices and systems to reliably predict and optimize the performance of high-power Ytterbium-doped fiber amplifier and laser systems. The ready availability of a flexible, user-friendly design tool should be of considerable practical interest to scientists and engineers working with this important new laser technology since Ytterbium amplifier and amplifier cascades are often difficult to optimize experimentally due to the three-level nature of the Ytterbium laser transition. As examples of the utility and accuracy of the software, as well as the complexity of the systems and amplifier properties that can be successfully modeled, we present a comparison of experimental and theoretical results for individual core and cladding pumped amplifiers, and also for an ultra-short pulse four-stage amplifier system optimized both to provide a broad gain bandwidth and to minimize nonlinear effects. We also show how high energy 100 ns pulses with complex user definable temporal profiles can be created in a gain-saturated amplifier by suitable pre-shaping of the low-energy input pulses. Furthermore, with appropriate modifications the same software package can be applied to fiber amplifiers based on other rare-earth elements and glass hosts.

The large loop excision of the transformation zone cut or blend thermal artefact study: a randomized controlled trial.

The objective of this randomized controlled trial was to determine whether the pure cut setting results in less thermal artefact than the traditional blend setting when performing a large loop excision of the transformation zone (LLETZ). Forty-nine consenting women were randomized to undergo an LLETZ procedure using either the pure cut or the blend setting. Two histopathologists, who were blind to the randomization, examined the specimens and then graded and measured the degree of thermal artefact. No significant difference was noted at the epithelial margin. At the deep stromal margins, in the blend group, the mean thickness of thermal artefact was 0.382 mm (95% CI, 0.350-0.414) and in the cut group 0.325 mm (95% CI, 0.297-0.353). This was statistically significant. No significant difference was detected in terms of grading of thermal artefact, the presence of dysplasia at the specimen margins, or in positive follow-up smears. Although there was less thermal artefact at the deep stromal margin, cautery at this margin does not generally interfere with pathological assessment of the specimen and the pure cut setting does not produce a clinically significant decrease in the degree of thermal artefact.

Efficacy of cervical intrarepithelial neoplasia (CIN) treatment by cold coagulation.

Our objective was to evaluate the efficacy of cold coagulation in the treatment of cervical intraepithelial neoplasia. The study design consisted of a retrospective review of case records of all women treated with cold coagulation from the colposcopy clinics inception in 1980 to 1994. A total of 725 women received treatment with cold coagulation. All grades of CIN were treated. 632 (87.1%) had long term negative follow up. 93 (12.6%) of patients had abnormal cytological follow up, but only 45 (6.2%) required re-treatment. Within the first year after treatment 52 (7.1%) patients presented with persistent cytological abnormalities, 32 (4.4%) required repeated treatment for persistent dyskaryosis. 41 (5.6%) of patients had recurrent cytological abnormalities, 13 (1.8%) required repeated treatment. Recurrence developed between two and 12 years from initial treatment. One case of cervical carcinoma following treatment with cold coagulation was recorded. Our data suggest that cold coagulation appears to be safe, efficient treatment for cervical intraepithelial neoplasia.

Morphological effects of chemotherapy on ovarian carcinoma.

AIMS: Traditionally, advanced stage ovarian carcinoma is treated by debulking surgery followed by chemotherapy. However, in some circumstances preoperative chemotherapy may be given before optimal surgical debulking. This study aims to describe the morphological features found in ovarian carcinoma after chemotherapy because these have not been detailed previously. METHODS: Histological sections were examined from 18 cases of ovarian carcinoma that had been treated by preoperative chemotherapy. The morphology was compared with any pre-chemotherapy biopsies that had been performed. Tumours were classified as showing morphological features suggesting a good response to chemotherapy (n = 14) or as showing little or no response (n = 4). Serum CA125 values before and after chemotherapy were compared. In all cases, the mitotic activity index (MAI), volume percentage of epithelium (VPE), and mean nuclear area (MNA) of tumour cells were calculated. RESULTS: The preoperative biopsies were all typical ovarian serous or endometrioid adenocarcinomas. Morphological features present in the group responding to chemotherapy included the presence of small groups or single tumour cells in a densely fibrotic stroma. Tumour cells were characterised by both nuclear and cytoplasmic alteration, making accurate tumour typing and grading impossible. Nuclear features included the presence of bizarre enlargement with hyperchromatism, irregularity of outline, and chromatin clumping or smudging. Cytoplasmic alterations included intense eosinophilia, vacuolation, or foam cell change. There were pronounced stromal changes of fibrosis, inflammation, collections of foamy histiocytes, cholesterol cleft formation, haemosiderin deposition, fat necrosis, and dystrophic calcification, including the presence of many free psammoma bodies. There was no correlation between morphological response and biochemical response, as determined by serum CA125 values. In all nine cases in which pre-chemotherapy and post-chemotherapy biopsies were available, the MNA increased post-chemotherapy (p = 0.007, paired Wilcoxon test) and in six of nine cases the MAI decreased (p = 0.093). CONCLUSIONS: Because preoperative chemotherapy is being used increasingly in the management of ovarian cancer, pathologists should be aware of the resultant morphological effects. Accurate tumour typing and grading is impossible. In some cases, it may be difficult to confirm the presence of residual tumour, making it imperative that pre-chemotherapy tissue biopsies are obtained. Definite confirmation of residual tumour may require the examination of multiple histological sections from areas showing pronounced stromal changes, sometimes with multiple levels and immunohistochemistry. In the absence of definite residual tumour, the report should state that the features are consistent with the prior presence of tumour.

Practical low-noise stretched-pulse Yb(3+)-doped fiber laser.

We report on the development of what we consider to be a practical and highly stable stretched-pulse laser based on Yb(3+) -doped silica fiber. The Fabry-Perot cavity uses nonlinear polarization rotation as the mode-locking mechanism, and a semiconductor saturable-absorber mirror to ensure robust self-starting and incorporates a diffraction grating pair to compensate for the normal dispersion of the fiber. Use of a single-mode grating-stabilized telecommunications-qualified pump laser diode ensures reliable, low-noise operation (~0.05% amplitude fluctuations at 10-Hz measurement bandwidth). The laser generates high-quality, 60-pJ pulses of <110-fs duration at a repetition rate of ~54 MHz (3-mW average power).

Synchronously pumped optical parametric oscillator driven by a femtosecond mode-locked fiber laser.

A femtosecond all-fiber laser source incorporating a cw mode-locked Yb-doped silica fiber oscillator and amplifier has been used to synchronously pump an optical parametric oscillator based on periodically poled lithium niobate. The signal output, consisting of 330-fs pulses at a 54-MHz repetition rate and average powers up to 90 mW, was tuned from 1.55 to 1.95microm , with a corresponding idler range of 2.30-3.31microm .

Primary grade teachers' knowledge and perceptions of head lice.

This study examined primary grade teachers' knowledge of head lice, perceived self-efficacy in dealing with head lice, and preferred resources of additional information on head lice. Survey data from a three-wave mailing (M = 292; 60%) found that teachers needed more knowledge regarding head lice and were significantly more knowledgeable as teaching experience increased. A plurality (46%) had high efficacy expectations scores regarding their ability to control the spread of head lice. Most (71%) primary teachers reported they received most of their head lice information from school nurses. Most (63%) said they would like more information on how to prevent head lice infestation, and they wanted the information in the form of videotapes (68%) and brochures (51%). Only 23% provided yearly instruction regarding head lice.