Setting the international research agenda for sarcomas with patients and carers: results of phase II of the Sarcoma Patient Advocacy Global Network (SPAGN) priority setting partnership.

BACKGROUND: Typically, researchers and clinicians determine the agenda in sarcoma research. However, patient involvement can have a meaningful impact on research. Therefore, the Patient-Powered Research Network (PPRN) of the Sarcoma Patient Advocacy Global Network (SPAGN) set up a Priority Setting Partnership (PSP). The primary objective of this partnership is to identify priorities for research and patient advocacy topics. METHODS: In the first phase of this PSP, including 264 sarcoma patients and carers from all over the world, 23 research topics regarding sarcomas and 15 patient advocacy topics were identified using an online survey. In the second phase, participants were asked to fill in a top five and a top three of research and patient advocacy topics, respectively. Additionally, sociodemographic characteristics and sarcoma characteristics were collected. Social media channels, local national patient advocacy groups and the SPAGN website were used to distribute the survey. RESULTS: In total, 671 patients (75%) and carers (25%) participated in this survey. The five highest ranked research topics were related to causes of sarcoma (43%), prognosis and risk of recurrence (40%), specific subtypes of sarcoma (33%), the role of immunotherapy, targeted therapy and combined therapy (30%), and hereditary aspects (30%). The three highest ranked patient advocacy topics were improving the diagnostic process of sarcoma (39%), access to tumor DNA analysis (37%) and establishing an international sarcoma registry (37%). CONCLUSIONS: This sarcoma PSP has identified priorities for research and patient advocacy, offering guidance for researchers, assisting funding agencies with assessing project relevance and empowering patient advocates to represent the needs of patients and carers.

Micro-fluorescence lifetime and spectral imaging of ytterbium doped laser materials.

We present the application of a confocal fluorescence microscope to the analysis of Yb-doped solid-state laser materials, with examples of Yb-doped crystals, photonic crystal fibers and fiber preforms made with different manufacturing processes. Beside the fluorescence lifetime image itself, a microscopic spectral fluorescence emission analysis is presented and spatially resolved emission cross sections are obtained. Doping concentration and its distributions and other laser optical parameters are measured, which help to analyze manufacturing steps. Further properties like photodarkening and saturation are addressed.

High-sensitivity dispersive Mach-Zehnder interferometer based on a dissimilar-doping dual-core fiber for sensing applications.

A dual-core fiber in which one of the cores is doped with germanium and the other with phosphorus is used as an in-line Mach-Zehnder dispersive interferometer. By ensuring an equal length but with different dispersion dependencies in the interferometer arms (the two cores), high-sensitivity strain and temperature sensing are achieved. Opposite sensitivities for high and low wavelength peaks were also demonstrated when strain and temperature was applied. To our knowledge this is the first time that such behavior is demonstrated using this type of in-line interferometer based on a dual-core fiber. A sensitivity of (0.102±0.002) nm/µÎµ, between 0 and 800 µÎµ and (-4.2±0.2) nm/°C between 47°C and 62°C is demonstrated.

Brillouin scattering properties of lanthano-aluminosilicate optical fiber.

Utilizing measurements on a lanthano-aluminosilicate core optical fiber, the specific effects of lanthana (La2O3) on the Brillouin characteristics of silica-based oxide glass optical fibers are described. Lanthana is an interesting species to investigate since it possesses a wide transparency window covering the common fiber laser and telecom system wavelengths. As might be expected, it is found that the properties of lanthana are very similar to those of ytterbia (Yb2O3), namely, low acoustic velocity, wide Brillouin spectral width, and a negative photoelastic constant, with the latter two properties affording significant reductions to the Brillouin gain coefficient. However, lanthana possesses thermo-acoustic and strain-acoustic coefficients (acoustic velocity versus temperature or strain, TAC and SAC, respectively) with signs that are opposed to those of ytterbia. The lanthano-aluminosilicate (SAL) fiber utilized in this study is Brillouin-athermal (no dependence of the Brillouin frequency on temperature), but not atensic (is dependent upon the strain), which is believed to be, to the best of our knowledge, the first demonstration of such a glass fiber utilizing a compositional engineering approach.

Multiplexing of six micro-displacement suspended-core Sagnac interferometer sensors with a Raman-Erbium fiber laser.

This work experimentally demonstrates a long-range optical fiber sensing network for the multiplexing of fiber sensors based on photonic crystal fibers. Specifically, six photonic crystal fiber sensors which are based on a Sagnac interferometer that includes a suspended-core fiber have been used. These sensors offer a high sensitivity for micro-displacement measurements. The fiber sensor network presents a ladder structure and its operation mode is based on a fiber ring laser which combines Raman and Erbium doped fiber amplification. Thus, we show the first demonstration of photonic crystal fiber sensors for remote measurement applications up to 75 km.

From mild to gangrenous cholecystitis, laparoscopic cholecystectomy is safe 24 hours a day.

OBJECTIVES: Laparoscopic cholecystectomy (LC) at night remains controversial. Prior studies have not controlled for disease severity. We analyzed outcomes of LC performed day vs. night while controlling for the Parkland Grading Scale for Cholecystitis (PGS). METHODS: Analysis of the AAST multicenter evaluation of cholecystitis database was performed. Exclusion criteria included non-operative cases, open operations, and missing PGS. Cases were divided based on operation start time. PGS was used to control for disease severity. Outcomes included operative time, use of bailout techniques and complications. RESULTS: Of 759 procedures identified, 16% were nighttime LC. No differences in demographics, comorbidities, physiologic variables and PGS were noted. Operative time (108.6 min vs 105.6), bailout techniques (8.3% vs 7.4%) and complications (9.9% vs 11.3%) were similar between groups. CONCLUSION: Regardless of severity, laparoscopic cholecystectomy is safe 24-h a day. Operations performed at night have a similar complication profile to those performed during the day.

Non-operative management of acute cholecystitis in the elderly.

BACKGROUND: Although cholecystectomy is the standard therapy for acute cholecystitis (AC), operative morbidity in the elderly may be high owing to medical co-morbidities and decreased physiological reserve. Outcomes of AC in the elderly have not been fully defined with regard to operative and long-term non-operative management. METHODS: Patients aged 65 years or over admitted to a tertiary care centre with a diagnosis of AC between January 2000 and December 2009 were reviewed retrospectively. Patient data, operative and postoperative details were obtained. To determine cholecystectomy rates in the non-operative group, medical records were reviewed, and patients and families were interviewed. RESULTS: A total of 290 patients underwent cholecystectomy during the index admission, of whom 59 (20·3 per cent) required conversion to open operation. Fifty-eight of these patients experienced 98 complications, including acute respiratory failure (27), pneumonia (18), myocardial infarction (16) and sepsis (15). Some 185 patients had non-operative treatment, of whom 67 underwent percutaneous cholecystostomy. Forty-four patients subsequently had elective cholecystectomy, with a complication rate of 23 per cent. One hundred and twenty-six patients were discharged without a plan for cholecystectomy; the rate of recurrent AC was 4 per cent among the two-thirds of patients followed to within 15 months of death. No deaths or major complications occurred among those with recurrent AC. CONCLUSION: Despite selection of the best elderly candidates for cholecystectomy, postoperative morbidity was significant. Medical management, with interval cholecystectomy only for recurrent AC, may be appropriate in selected patients.

High precision micro-displacement fiber sensor through a suspended-core Sagnac interferometer.

A sensing system for micro-displacement measurement based in a suspended-core fiber Sagnac interferometer is presented. The suspended-core fiber characterization was made through the use of an optical backscatter reflectometer, screening its multimodal and birefringent behavior. Its sensitivity to displacement measurements is shown to be due only to birefringence, being that core-cladding mode coupling is negligible. High precision (~0.45 µm) was obtained using three different measurement instruments, showing an extremely high stability and high insensitivity to temperature, demonstrating that the sensing system has the ability for low cost applications.

Setting the international research agenda for sarcoma together with patients and carers: first results of the Sarcoma Patient EuroNet (SPAEN) priority setting partnership.

BACKGROUND: Research in sarcomas has historically been the domain of scientists and clinicians attempting to understand the disease to develop effective treatments. This traditional approach of placing scientific rigor before the patient's reality is changing. This evolution is reflected in the growth of patient-centered organizations and patient advocacy groups that seek to meaningfully integrate patients into the research process. The aims of this study are to identify the unanswered questions regarding sarcomas (including gastrointestinal stromal tumors and desmoid fibromatosis) from patient, carer, and clinical perspectives and examine how patients and carers want to be involved in sarcoma research. METHODS: The Patient-Powered Research Network of Sarcoma Patients EuroNet set up a Priority Setting Partnership (PSP) in collaboration with stakeholders from the sarcoma research field. This PSP is largely based on the James Lind Alliance methodology. RESULTS: In total, 264 sarcoma patients (73%) and carers (27%) from all over the world participated in the online survey and covered the full spectrum of sarcomas. The topics mentioned were labeled in accordance with the Common Scientific Outline of the International Cancer Research Partnership and lists for potential research topics, advocacy topics, and requests for information were constructed. With regard to patient and carer involvement, 64% were very willing to be actively involved and mainly in the following areas: sharing perspectives, discussing patient-clinician interactions, and attending research meetings. CONCLUSIONS: The first results of this sarcoma PSP identified important research questions, but also important topics for patient advocacy groups and further improvement of information materials. Sarcoma patients and carers have a strong wish to be involved in multiple aspects of sarcoma research. The next phase will identify the top 10 research priorities per tumor type. These priorities will provide guidance for research that will achieve greatest value and impact.

Suspended-core fiber Sagnac combined dual-random mirror Raman fiber laser.

In the present work, a multiwavelength fiber laser based in the combination of a double-random mirror and a suspended-core Sagnac interferometer is presented. The double-random mirror acts by itself as a random laser, presenting a 30dB SNR, as result of multiple Rayleigh scattering events produced in the dispersion compensating fibers by the Raman amplification. The suspended-core fiber Sagnac interferometer provides the multi peak channeled spectrum, which can be tuned by changing the length of the fiber. The result of this combination is a stable multiwavelength peak laser with a minimum of ~25dB SNR, which is highly sensitive to polarization induced variations.

Simultaneous measurement of curvature and strain using a suspended multicore fiber.

A suspended multicore fiber sensor for simultaneous measurement of curvature and strain is proposed. The spectral response shows evidences of several interferences arising from the seven cores of the fiber. Once the sensing head presents different sensitivities for curvature and strain measurements, these physical parameters can be discriminated by using the matrix method. The rms deviations are ±19 m(-1) and ±12.90 µÎµ for curvature and strain measurements, respectively.

Three-dimensional light bullets in arrays of waveguides.

We report the first experimental observation of three-dimensional light bullets, excited by femtosecond pulses in a system featuring quasi-instantaneous cubic nonlinearity and a periodic, transversally modulated refractive index. Stringent evidence of the excitation of light bullets is based on time-gated images and spectra which perfectly match our numerical simulations. Furthermore, we reveal a novel evolution mechanism forcing the light bullets to follow varying dispersion or diffraction conditions, until they leave their existence range and decay.

Material-dependent growth of human skin bacteria on textiles investigated using challenge tests and DNA genotyping.

AIMS: To investigate the influence of different fibre materials on the colonization of textiles by skin bacteria present in human sweat. METHODS AND RESULTS: The total bacterial content of axillary sweat samples was determined using DNA quantification, and the diversity of bacteria present was investigated. Fabrics made of different fibres were then challenged with these sweat samples; the bacterial DNA was quantified, and the bacterial taxa present were determined. We found differences in the overall colonization, with polyester and polyamide showing the highest bacterial mass. Also, significant differences in the various taxa of bacteria present on the different materials were found. In general, synthetic materials showed a selective growth of bacterial taxa underrepresented in sweat. In contrast, a cellulose-based material showed only very few taxa, identically with those predominant in sweat. CONCLUSIONS: Our investigations demonstrated that besides the bacterial content of sweat itself, the type of material has a strong impact on the bacterial colonization of textiles. SIGNIFICANCE AND IMPACT OF THE STUDY: Odour generation is one of several effects resulting from an interaction of skin bacteria with textiles, and it is a common experience that there are differences in odour generation by different materials. Our investigations suggest that a selective growth of potentially odour-producing bacteria may account for this.

Two-dimensional high-precision fiber waveguide arrays for coherent light propagation.

Fiber waveguide arrays can be applied as a very useful tool for the investigation of effects in discrete optics. The observation of coherent propagation in such discrete waveguide arrays requires, however, high structural precision and great material homogeneity. The fabrication of such a fiber array with close tolerances compared to conventional fiber technology is discussed. Linear propagation effects are modeled for an ideal fiber waveguide array and are compared with experimental results. The good agreement of these results with each other indicates the applicability of such fiber waveguide arrays in studying linear and non-linear properties in discrete optics.

Porcine skin visible lesion thresholds for near-infrared lasers including modeling at two pulse durations and spot sizes.

With the advent of such systems as the airborne laser and advanced tactical laser, high-energy lasers that use 1315-nm wavelengths in the near-infrared band will soon present a new laser safety challenge to armed forces and civilian populations. Experiments in nonhuman primates using this wavelength have demonstrated a range of ocular injuries, including corneal, lenticular, and retinal lesions as a function of pulse duration. American National Standards Institute (ANSI) laser safety standards have traditionally been based on experimental data, and there is scant data for this wavelength. We are reporting minimum visible lesion (MVL) threshold measurements using a porcine skin model for two different pulse durations and spot sizes for this wavelength. We also compare our measurements to results from our model based on the heat transfer equation and rate process equation, together with actual temperature measurements on the skin surface using a high-speed infrared camera. Our MVL-ED50 thresholds for long pulses (350 micros) at 24-h postexposure are measured to be 99 and 83 J cm(-2) for spot sizes of 0.7 and 1.3 mm diam, respectively. Q-switched laser pulses of 50 ns have a lower threshold of 11 J cm(-2) for a 5-mm-diam top-hat laser pulse.

Real-time detection of nitric oxide isotopes in lung function tests.

In lung function tests, the determination of the pulmonary diffusing capacity (D) using the single-breath method is a commonly applied technique. The calculation of D is performed on the basis of accurate measurements of indicator gas concentrations. In this chapter, we demonstrate the appropriateness of the stable nitric oxide (NO) isotopes 14NO and 15NO in revealing reliable data of D. We performed studies on animals (14NO) by using respiratory mass spectrometry (M3) and on humans (15NO) by applying laser magnetic resonance spectroscopy (LMRS). The equipment was characterized by sufficient detection limits of 70 parts/billion at [14NO] = 0.001% (M3) and 40 parts/billion at [15NO] = 0.002 % (LMRS), respectively. Lastly, we were able to show that D-values for 14NO indeed reveal the entire diffusive properties of the alveolar-capillary membrane and that 15NO is a useful indicator gas for reflecting disturbances of pulmonary gas exchange.

Vitamin B6 status of low-income adolescent and adult pregnant women and the condition of their infants at birth.

The vitamin B6 status of 127 low-income pregnant adolescent and adult women was assessed at two stages of pregnancy and related to the condition of the infant at birth. The mean dietary intake of vitamin B6 for a subsample of 57 of the subjects at the initial prenatal clinic visit was 1.37 +/- 1.02 mg (mean +/- SD). The mean stimulation of erythrocyte alanine aminotransferase activity by pyridoxal 5'-phosphate was 34.8 +/- 21.1% at the first clinic visit and 29.4 +/- 14.5% for a subsample of 30 subjects at the 30th wk of pregnancy. Apgar scores of infants whose mothers had high erythrocyte alanine aminotransferase stimulation values (greater than 25%) were significantly lower (p less than or equal to 0.05) than infants whose mothers had normal erythrocyte alanine aminotransferase stimulation values (less than or equal to 25%). These data indicate a vitamin B6 deficiency at two stages of pregnancy in these low-income adolescent and adult women and lower Apgar scores in infants whose mothers were vitamin B6 deficient than those with adequate vitamin B6 status.

Urinary 4-pyridoxic acid excretion in 24-hour versus random urine samples as a measurement of vitamin B6 status in humans.

Urinary excretion of 4-pyridoxic acid (4PA) in 19 men (n = 5) and women (n = 14) was measured to evaluate the validity of determining the 4PA/creatinine ratio in random urine samples as an alternative to total 24-h 4PA excretion in assessing vitamin B6 nutritional status. The relationships among dietary vitamin B6 intake, 4PA excretion, plasma pyridoxal 5'-phosphate levels, and erythrocyte aspartate aminotransferase activity and in vitro stimulation by added plasma pyridoxal 5'-phosphate were examined. The subjects consumed all meals for 3 days in a metabolic unit, and protein intake was kept constant. Plasma pyridoxal 5'-phosphate concentration was positively correlated with vitamin B6 intake of the previous day (r = 0.61, p less than 0.01). There was a positive correlation (r = 0.59, p less than 0.01) between total 4PA and 4PA/creatinine in the 24-h urine samples. No difference (p greater than 0.05) in 4PA/creatinine between the 24-h samples and either morning or afternoon random samples taken the next day was found. These findings support the use of the 4PA/creatinine ratio in random urine samples as an alternative to 24-h urinary 4PA excretion.

The pharmacokinetics of metoprolol and its metabolites in dialysis patients.

The kinetics of tritiated metoprolol and its metabolites have been determined after intravenous and oral administration in dialysis patients. The kinetic behaviour of metoprolol in these patients does not differ from that in healthy volunteers, since its elimination depends on hepatic metabolism. The pharmacologically less active metabolite alpha-hydroxymetoprolol is formed to an individually varying degree and its half-life is prolonged. The concentration of the total radioactivity, which represents the sum of all metabolites, does not decline in the dialysis interval. During haemodialysis, however, its concentration decreases with a half-life of 5h. It might be assumed, that dialysis of these polar compounds is rather nonspecific and that it depends essentially on the dialysis technique.

Heterophile antibodies indicate progression of autoimmunity in human type 1 diabetes mellitus before clinical onset.

We previously reported serum cytokines in a group of long term non-progressors to Type 1 diabetes; this reactivity detected in ELISA is now identified as heterophile antibody in some sera. Here, we characterize heterophile antibody activity. A 14 kDa-polypeptide from heterophile antibody containing serum bound to an anti-IL-4 column, but IL-4 was not detected by Western blot or by MS/MS sequencing. However, in 2/13 heterophile antibody positive sera, T-cell growth was potentiated and was blocked by an anti-human immunoglobulin. To examine the relationship between low affinity heterophile antibody presence and disease progression, 1100 archived serum samples were analyzed with two pairs of antibodies from 443 diabetes-free first degree relatives of Type 1 diabetes mellitus patients for heterophile antibody; 95 individuals developed diabetes on follow-up. Twenty-two individuals, whose serum was heterophile antibody positive with the second pair of antibodies (but negative with the first pair of antibodies), had a significantly higher incidence of developing diabetes after five years. Thirty-seven individuals with heterophile antibody reactivity with the first pair of antibodies, regardless of reactivity with the second pair of antibodies, had a significantly lower incidence of developing diabetes. While we cannot exclude the presence of genuine cytokine in all sera, these data indicate the presence of distinct groups of heterophile antibodies in patients at high risk to develop diabetes. Thus, anti-Ig heterophilic antibodies with different immunochemical reactivities are linked to the progression of or protection from Type 1 diabetes autoimmunity.