Organisation of Prostate Cancer Services in the English National Health Service.

AIMS: The National Prostate Cancer Audit (NPCA) started in April 2013 with the aim of assessing the process of care and its outcomes in men diagnosed with prostate cancer in England and Wales. One of the key aims of the audit was to assess the configuration and availability of specialist prostate cancer services in England. MATERIALS AND METHODS: In 2014, the NPCA undertook an organisational survey of all 143 acute National Health Service (NHS) Trusts and 48 specialist multidisciplinary team (MDT) hubs cross England. Questionnaires established the availability and location of core diagnostic, treatment and patient-centred support services for the management of non-metastatic prostate cancer in addition to specific diagnostic and treatment procedures that reflect the continuing evolution of prostate cancer management, such as high-intensity focused ultrasound (HIFU) and stereotactic body radiotherapy. RESULTS: The survey received a 100% response rate. The results showed considerable geographical variation with respect to the availability of core treatment modalities, the size of the target population and catchment areas served by specialist MDT hubs, as well as in the uptake of additional procedures and services. Specifically there are gaps in the availability of core radiotherapy procedures; high dose rate and low dose rate brachytherapy are available in 44% and 75% of specialist MDTs, respectively. By comparison, there seems to be a relative 'over-penetration' of surgical innovation, with 67% of specialist MDTs providing robotic-assisted laparoscopic prostatectomy and 21% HIFU. There is also evidence of increased centralisation of core surgical procedures and regional inequity in the availability of surgical innovation across England. CONCLUSIONS: The organisational survey of the NPCA has provided a comprehensive assessment of the structure and function of specialist MDTs in England and the availability of prostate cancer procedures and services. As part of the prospective audit, the NPCA will assess the effect of the availability of prostate cancer services on access regionally and subsequent outcomes of care according to evidence-based guidelines

Carrier and Light Trapping in Graded Quantum Well Laser Structures

We investigated the carrier and light trapping in GaInAs/AlGaAs single quantum well laser structures by means of time resolved photoluminescence and Raman spectroscopy. The influence of the shape and depth of the confinement potential and of the cavity geometry was studied by using different AlGaAs/GaAs short-period superlattices as barriers. Our results show that grading the optical cavity improves considerably both carrier and light trapping in the quantum well, and that the trapping efficiency is enhanced by increasing the graded confining potential.Comment: PDF-format, 15 pages (including 4 figures), Applied Physics Letters (June 2000

Centralisation of services for children with cleft lip or palate in England: a study of hospital episode statistics.

BACKGROUND: In 1998, a process of centralisation was initiated for services for children born with a cleft lip or palate in the UK. We studied the timing of this process in England according to its impact on the number of hospitals and surgeons involved in primary surgical repairs. METHODS: All live born patients with a cleft lip and/or palate born between April 1997 and December 2008 were identified in Hospital Episode Statistics, the database of admissions to English National Health Service hospitals. Children were included if they had diagnostic codes for a cleft as well as procedure codes for a primary surgical cleft repair. Children with codes indicating additional congenital anomalies or syndromes were excluded as their additional problems could have determined when and where they were treated. RESULTS: We identified 10,892 children with a cleft. 21.0% were excluded because of additional anomalies or syndromes. Of the remaining 8,606 patients, 30.4% had a surgical lip repair only, 41.7% a palate repair only, and 28.0% both a lip and palate repair. The number of hospitals that carried out these primary repairs reduced from 49 in 1997 to 13, with 11 of these performing repairs on at least 40 children born in 2008. The number of surgeons responsible for repairs reduced from 98 to 26, with 22 performing repairs on at least 20 children born in 2008. In the same period, average length of hospital stay reduced from 3.8 to 3.0 days for primary lip repairs, from 3.8 to 3.3 days for primary palate repairs, and from 4.6 to 2.6 days for combined repairs with no evidence for a change in emergency readmission rates. The speed of centralisation varied with the earliest of the nine regions completing it in 2001 and the last in 2007. CONCLUSIONS: Between 1998 and 2007, cleft services in England were centralised. According to a survey among patients' parents, the quality of cleft care improved in the same period. Surgical care became more consistent with current recommendations. However, key outcomes, including facial appearance and speech, can only be assessed many years after the initial surgical treatment

Grommet Surgery in Children With Orofacial Clefts in England.

OBJECTIVE: To assess grommet insertion practice in the first 5 years of life among children with an orofacial cleft in England. DESIGN: Analysis of national administrative data of hospital admissions. SETTING: National Health Service hospitals, England. PATIENTS: Patients born between 1997 and 2005 who underwent surgical cleft repair. INTERVENTION: Children receiving grommets before the age of 5 years. OUTCOME MEASURES: The proportion of children receiving grommets before the age of 5 years, the timing of the first grommet insertion, and the proportion of children having repeat grommet insertions were examined according to cleft type, the absence or presence of additional anomalies, socioeconomic deprivation, and region of residence. RESULTS: The study included 8,269 children. Before the age of 5 years, 3,015 (36.5%) children received grommets. Of these, 33.2% received their first grommets at primary cleft repair and 33.3% underwent multiple grommet insertion procedures. The most common age for the first procedure was between 6 and 12 months. Children with a cleft affecting the palate were more likely to receive grommets than children with a cleft lip alone (45.5% versus 4.5%). Grommet insertion practice also varied according to year of birth, absence or presence of additional anomalies, socioeconomic deprivation, and region of residence. CONCLUSION: Grommets practice in children with a cleft appears to vary according to their clinical characteristics. The differences in practice observed according to deprivation and region of residence need to be further explored

A novel doxorubicin-glucuronide prodrug DOX-GA3 for tumour-selective chemotherapy: distribution and efficacy in experimental human ovarian cancer

The doxorubicin (DOX) prodrug N -[4-doxorubicin- N -carbonyl (oxymethyl) phenyl] O -β-glucuronyl carbamate (DOX-GA3) was synthesised for specific activation by human β-glucuronidase, which is released in necrotic areas of tumour lesions. This novel prodrug was completely activated to the parent drug by human β-glucuronidase with V max= 25.0 μmol min–1mg–1and K m= 1100 μM. The pharmacokinetics and distribution of DOX-GA3 in nude mice bearing human ovarian cancer xenografts (OVCAR-3) were determined and compared with DOX. Administration of DOX at 8 mg kg–1i.v. (maximum tolerated dose, MTD) to OVCAR-3-bearing mice resulted in a peak plasma concentration of the drug of 16.4 μM (t = 1 min). A 7.6-times lower peak plasma concentration of DOX was measured after injection of DOX-GA3 at 250 mg kg–1i.v. (50% of MTD). In normal tissues the prodrug showed peak DOX concentrations that were up to 5-fold (heart) lower than those found after DOX administration. DOX-GA3 activation by β-glucuronidase in the tumour yielded an almost 5-fold higher DOX peak concentration of 9.57 nmol g–1(P< 0.05) than the peak concentration of only 2.14 nmol g–1observed after DOX. As a consequence, the area under the curve of DOX calculated in tumour tissue after DOX-GA3 (13.1 μmol min–1g–1) was 10-fold higher than after DOX (1.31 μmol min–1g–1). The anti-tumour effects of DOX-GA3 and DOX were compared at equitoxic doses in OVCAR-3 xenografts at a mean tumour size of 125 mm3. The prodrug given i.v. at 500 mg kg–1weekly × 2 resulted in a maximum tumour growth inhibition of 87%, while the standard treatment with DOX at a dose of 8 mg kg–1i.v. weekly × 2 resulted in a maximum tumour growth inhibition of only 56%. Treatment with DOX-GA3 was also given to mice with larger tumours containing more necrosis. For tumours with a mean size of 400 mm3the specific growth delay by DOX-GA3 increased from 2.7 to 3.9. Our data indicate that DOX-GA3 is more effective than DOX and suggest that the prodrug will be specifically advantageous for treatment of advanced disease. © 2001 Cancer Research Campaign http://www.bjcancer.co

Piezoelectric exciton-acoustic phonon coupling in single quantum dots

Micro-photoluminescence spectroscopy at variable temperature, excitation intensity and energy was performed on a single InAs/AlAs self-assembled quantum dot. The exciton emission line (zero-phonon line, ZPL) exhibits a broad sideband due to exciton-acoustic phonon coupling by the deformation potential mechanism. Additionally, narrow low-energy sidebands at about 0.25 meV of the ZPL are attributed to exciton-acoustic phonon piezoelectric coupling. In lowering the excitation energy or intensity these bands gradually dominate the emission spectrum of the quantum dot while the ZPL disappears. At high excitation intensity the sidebands due to piezoelectric coupling decrease strongly and the ZPL dominates the spectrum as a consequence of screening of the piezoelectric coupling by the photocreated free carriers.Comment: 4 pages, 4 figure

Gamma-Ray Spectra & Variability of the Crab Nebula Emission Observed by BATSE

We report ~ 600 days of BATSE earth-occultation observations of the total gamma-ray (30 keV to 1.7 MeV) emission from the Crab nebula, between 1991 May 24 (TJD 8400) and 1994 October 2 (TJD 9627). Lightcurves from 35-100, 100-200, 200-300, 300-400, 400-700, and 700-1000 keV, show that positive fluxes were detected by BATSE in each of these six energy bands at significances of approximately 31, 20, 9.2, 4.5, 2.6, and 1.3 sigma respectively per day. We also observed significant flux and spectral variations in the 35-300 keV energy region, with time scales of days to weeks. The spectra below 300 keV, averaged over typical CGRO viewing periods of 6-13 days, can be well described by a broken power law with average indices of ~ 2.1 and ~ 2.4 varying around a spectral break at ~ 100 keV. Above 300 keV, the long-term averaged spectra, averaged over three 400 d periods (TJD 8400-8800, 8800-9200, and 9200-9628, respectively) are well represented by the same power law with index of ~ 2.34 up to ~ 670 keV, plus a hard spectral component extending from ~ 670 keV to ~ 1.7 MeV, with a spectral index of ~ 1.75. The latter component could be related to a complex structure observed by COMPTEL in the 0.7-3 MeV range. Above 3 MeV, the extrapolation of the power-law continuum determined by the low-energy BATSE spectrum is consistent with fluxes measured by COMPTEL in the 3-25 MeV range, and by EGRET from 30-50 MeV. We interpret these results as synchrotron emission produced by the interaction of particles ejected from the pulsar with the field in different dynamical regions of the nebula system, as observed recently by HST, XMM-Newton, and Chandra.Comment: To be published in the November 20, 2003, Vol 598 issue of the Astrophysical Journa

Non-parametric Bayesian drift estimation for stochastic differential equations

We consider non-parametric Bayesian estimation of the drift coefficient of a one-dimensional stochastic differential equation from discrete-time observations on the solution of this equation. Under suitable regularity conditions that are weaker than those previosly suggested in the literature, we establish posterior consistency in this context. Furthermore, we show that posterior consistency extends to the multidimensional setting as well, which, to the best of our knowledge, is a new result in this setting.Comment: 27 page