Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies.

Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease.

Evaluation of individual dosimetry in mixed neutron and photon radiation fields (EVIDOS). Part I: Scope and methods of the project.

Supported by the European Commission, the EVIDOS project started in November 2001 with the broad goal of evaluating state of the art dosimetry techniques in representative workplaces of the nuclear industry. Seven European institutes joined efforts with end users at nuclear power plants, at fuel processing and reprocessing plants, and at transport and storage facilities. A comprehensive programme was devised to evaluate capabilities and limitations of standard and innovative personal dosemeters in relation to the mixed neutron-photon fields of concern to the nuclear industry. This paper describes the criteria behind the selection of dosimetry techniques and workplaces that were analysed, as well as the organisation of the measurement campaigns. Particular emphasis was placed on the evaluation of a variety of electronic personal dosemeters, either commercially available or previously developed by the partners. The estimates provided by these personal dosemeters were compared to reference values of dose equivalent quantities derived from spectrometry and fluence-to-dose equivalent conversion coefficients. Spectrometry was performed both with conventional multisphere and with some original instrumentation providing energy and direction resolution, based on silicon detectors and superheated drop detectors mounted on or in spherical moderators. The results were collected in a large, searchable database and are intended to be used in the harmonisation of dosimetric procedures for mixed radiation fields and for the approval of dosimetry services in Europe.

Evaluation of individual dosimetry in mixed neutron and photon radiation fields (EVIDOS). Part II: Conclusions and recommendations.

The paper presents the main conclusions and recommendations derived from the EVIDOS project, which is supported by the European Commission within the 5th Framework Programme. EVIDOS aims at evaluating state of the art neutron dosimetry techniques in representative workplaces of the nuclear industry with complex mixed neutron-photon radiation fields. This analysis complements a series of individual papers which present detailed results and it summarises the main findings from a practical point of view. Conclusions and recommendations are given concerning characterisation of radiation fields, methods to derive radiation protection quantities and dosemeter results.

Electronic neutron personal dosemeters: their performance in mixed radiation fields in nuclear power plants.

This work describes spectral distributions of neutrons obtained as function of energy and direction at four workplace fields at the Krümmel reactor in Germany. Values of personal dose equivalent H(p)(10) and effective dose E are determined for different directions of a person's orientation in these fields and readings of personal neutron dosemeters--especially electronic dosemeters--are discussed with respect to H(p)(10) and E.

Characterisation of the TAPIRO BNCT epithermal facility.

A collimated epithermal beam for boron neutron capture therapy (BNCT) research has been designed and built at the TAPIRO fast research reactor. A complete experimental characterisation of the radiation field in the irradiation chamber has been performed, to verify agreement with IAEA requirements. Slow neutron fluxes have been measured by means of an activation technique and with thermoluminescent detectors (TLDs). The fast neutron dose has been determined with gel dosemeters, while the fast neutron spectrum has been acquired by means of a neutron spectrometer based on superheated drop detectors. The gamma-dose has been measured with gel dosemeters and TLDs. For an independent verification of the experimental results, fluxes, doses and neutron spectra have been calculated with Monte Carlo simulations using the codes MCNP4B and MCNPX_2.1.5 with the direct statistical approach (DSA). The results obtained confirm that the epithermal beams achievable at TAPIRO are of suitable quality for BNCT purposes.

Individual neutron monitoring in workplaces with mixed neutron/photon radiation.

EVIDOS ('evaluation of individual dosimetry in mixed neutron and photon radiation fields') is an European Commission (EC)-sponsored project that aims at a significant improvement of radiation protection dosimetry in mixed neutron/photon fields via spectrometric and dosimetric investigations in representative workplaces of the nuclear industry. In particular, new spectrometry methods are developed that provide the energy and direction distribution of the neutron fluence from which the reference dosimetric quantities are derived and compared to the readings of dosemeters. The final results of the project will be a comprehensive set of spectrometric and dosimetric data for the workplaces and an analysis of the performance of dosemeters, including novel electronic dosemeters. This paper gives an overview of the project and focuses on the results from measurements performed in calibration fields with broad energy distributions (simulated workplace fields) and on the first results from workplaces in the nuclear industry, inside a boiling water reactor and around a spent fuel transport cask.

In-phantom dosimetry and spectrometry of photoneutrons from an 18 MV linear accelerator.

A combination of three superheated drop detectors with different neutron energy responses was developed to evaluate dose-equivalent and energy distributions of photoneutrons in a phantom irradiated by radiotherapy high-energy x-ray beams. One of the three detectors measures the total neutron dose equivalent and the other two measure the contributions from fast neutrons above 1 and 5.5 MeV, respectively. In order to test the new method, the neutron field produced by the 10 cm X 10 cm x-ray beam of an 18 MV radiotherapy accelerator was studied. Measurements were performed inside a tissue-equivalent liquid phantom, at depths of 1, 5, 10 and 15 cm and at lateral distances of 0, 10, and 20 cm from the central axis. These data were used to calculate the average integral dose to the radiotherapy patient from direct neutrons as well as from neutrons transmitted through the accelerator head. The characteristics of the dosimeters were confirmed by results in excellent agreement with those of prior studies. Track etch detectors were also used and provided an independent verification of the validity of this new technique. Within the primary beam, we measured a neutron entrance dose equivalent of 4.5 mSv per Gy of photons. It was observed that fast neutrons above 1 MeV deliver most of the total neutron dose along the beam axis. Their relative contribution increases with depth, from about 60% at the entrance to over 90% at a depth of 10 cm. Thus, the average energy increases with depth in the phantom as neutron spectra harden.

A multicenter evaluation of a single-pass lead VDD pacing system. The Multicenter Study Group.

Since June 1985 until April 1989, 237 patients (130 males, 107 females, aged 22 to 95 years, mean 71) with symptomatic AV conduction disturbances and competent sinus node, were implanted with a single-pass lead VDD pacing system in 30 centers and followed-up for at least 6 months. The ventricular pacing lead incorporated two atrial ring 3-cm apart electrodes, positioned within the right atrial cavity without contact with the heart wall, in order to detect the atrial activity, which is differentially processed by the pacemaker. At implant, mean atrial electrogram amplitude, derived from a custom pacemaker system analyzer (PSA) with the same input filter of the pacemaker was 1.7 +/- 0.8 mV (n = 93). In all cases, atrial sensitivity at implant was the default value +/- 0.15 mV. The atrial tracking capability of the pacing systems was assessed within the month and every 6 months after implantation by means of clinical evaluation, resting ECG, 24-hour Holter monitoring and the following tests: exercise stress testing, mental stress, isometric exercise, and nifedipine test. These tests evoke an increase of atrial rate in consequence of metabolic needs or as a reflex response. The criterion used to evaluate the correct operation of the system was the percentage of atrial synchronization. This was defined as the ratio between atrial triggered ventricular paced complexes and all ventricular paced complexes. All monitorings showed a ratio higher than or equal to 98% in a percentage of patients not lower than 95%. Mean follow-up was 385 days (range 183-1,370 days).(ABSTRACT TRUNCATED AT 250 WORDS)

[The acupuncture in 20 patients submitted to placement of endocardial permanent pacemakers (author's transl)]. / Impiego dell'agopuntura in 20 pazienti sottoposti ad impianto di pacemaker definitivo endocavitario.

The Authors report on 20 patients who underwent definitive surgery for placement of artificial pacemaker with utilisation of acupuncture for analgesic purposes. The report in detail on the results obtained with even, in the light of a limited experience, can be considered positive.