Revisiting the T-cell receptor alpha/delta locus and possible associations with multiple sclerosis.

A role for T cells in the pathogenesis of multiple sclerosis (MS) is well supported, evidenced by myriad immunological studies, as well as the unequivocal genetic influence of the major histocompatibility complex (MHC). Despite many attempts, no convincing genetic associations have been made between T-cell receptor (TCR) gene loci and MS. However, these studies may not be definitive because of small sample sizes and under-representative marker coverage of the chromosomal regions being investigated. To explore potential roles between the TCR alpha locus and MS, we have genotyped a large family-based cohort, including 1360 affected individuals and 1659 of their unaffected first-degree relatives, at 40 single-nucleotide polymorphism (SNP) markers within the TCR alpha/delta locus. This represents the largest TCR alpha-MS study to date. From this screen, we identified three potential loci of interest in TCR alpha variable and constant gene regions using the transmission disequilibrium test. Although SNPs implicating each of these regions of interest will require genotyping in independent replication cohorts, these findings suggest a role for TCR gene polymorphisms in MS susceptibility. In the context of these findings we review the evidence.

Neutron spectrometry with a monolithic silicon telescope.

A neutron spectrometer was set-up by coupling a polyethylene converter with a monolithic silicon telescope, consisting of a DeltaE and an E stage-detector (about 2 and 500 microm thick, respectively). The detection system was irradiated with monoenergetic neutrons at INFN-Laboratori Nazionali di Legnaro (Legnaro, Italy). The maximum detectable energy, imposed by the thickness of the E stage, is about 8 MeV for the present detector. The scatter plots of the energy deposited in the two stages were acquired using two independent electronic chains. The distributions of the recoil-protons are well-discriminated from those due to secondary electrons for energies above 0.350 MeV. The experimental spectra of the recoil-protons were compared with the results of Monte Carlo simulations using the FLUKA code. An analytical model that takes into account the geometrical structure of the silicon telescope was developed, validated and implemented in an unfolding code. The capability of reproducing continuous neutron spectra was investigated by irradiating the detector with neutrons from a thick beryllium target bombarded with protons. The measured spectra were compared with data taken from the literature. Satisfactory agreement was found.

Ações de vigilância à saúde integradas à Atenção Primária à Saúde diante da pandemia da COVID-19: contribuições para o debate / Primary care-based health surveillance actions in response to the COVID-19 pandemic: contributions to the debate

Resumo Trata-se de uma revisão de síntese integrativa com objetivo de refletir sobre os desafios atinentes às ações de vigilância em saúde no enfrentamento da COVID-19, no âmbito da Atenção Primária à Saúde (APS), em sistemas de saúde de países selecionados. Foram incluídos, no estudo, países com modelos de APS distintos, mas que adotaram a vigilância nos territórios como premissa para o controle da transmissão da COVID-19. Houve a revisão bibliográfica da literatura científica e a análise documental de normas e diretrizes relacionadas à organização da APS para enfrentamento da pandemia. A produção dos dados ocorreu no período entre abril e julho de 2020 e envolveu a busca de documentos sobre o enfrentamento da COVID-19, no que se refere à APS, nos sites oficiais governamentais de cada país e nas bases de dados científicas Web of Science e Science Direct. Ações integradas de vigilância em saúde demonstraram atuação mais direcionada sobre riscos, sendo possível respostas inovadoras e mais efetivas para enfrentamento da COVID-19, considerando necessidades emergentes no âmbito da APS. Contudo, experiências desenvolvidas por alguns países apresentaram controvérsias éticas e operacionais além dos desafios de acesso às tecnologias decorrente das desigualdades sociais.

Abstract We conducted an integrated literature review aimed at reflecting on the challenges related to primary care-based health surveillance actions in response to the COVID-19 pandemic in selected countries. The study included countries with different PHC models that adopted surveillance as an approach to control the transmission of COVID-19. We performed a search in October 2020 for relevant literature and norms and guidelines related to the organization of primary health care (PHC) in response to the pandemic on official government websites and the databases Web of Science and Science Direct. The integrated health surveillance actions demonstrated that efforts were more focused on risks, with some countries adopting innovative and effective measures to respond to COVID-19, considering emerging needs within PHC. However, in addition to ethical controversies and operational difficulties, access to technology was a challenge in actions developed by some countries due to social inequalities.

Performance of a neutron spectrometer based on a PIN diode.

The neutron spectrometer discussed in this work consists of a PIN diode coupled with a polyethylene converter. Neutrons are detected through the energy deposited by recoil-protons in silicon. The maximum detectable energy is -6 MeV and is imposed by the thickness of the fully depleted layer (300 microm for the present device). The minimum detectable energy which can be assessed with pulse-shape discrimination (PSD) is -0.9 MeV. PSD is performed with a crossover method and setting the diode in the 'reverse-injection' configuration (i.e. with the N+ layer adjacent to the converter). This configuration provides longer collection times for the electron-hole pairs generated by the recoil-protons. The limited interval of detectable energies restricts the application of this spectrometer to low-energy neutron fields, such as the ones which can be produced at facilities hosting low-energy ion accelerators. The capacity to reproduce continuous neutron spectra was investigated by optimising the electronic chain for pulse-shape discrimination. In particular, the spectrometer was irradiated with neutrons that were generated by striking a thick beryllium target with protons of several energies and the measured spectra were compared with data taken from the literature.

Neutron fluxes in radiotherapy rooms.

The spatial distribution of the neutron flux, originated in an electron accelerator therapy room when energies above the threshold of (y,n) and (e,e'n) reactions are employed, is physically due to a direct flux, coming from the accelerator head, and to a flux diffused from the walls. In this work, the flux is described to a high degree of approximation by a set of functions whose spatial behavior is univocally determined by the angular distributions of the neutrons emitted from the shield of the accelerator head and diffused from the walls. The analytical results are verified with an extended series of Monte Carlo simulations obtained with the MCNP code.

Neutron measurements around medical electron accelerators by active and passive detection techniques.

Passive and active detection techniques have been employed in order to measure neutron fluence rates and corresponding exposure rates around medical electron accelerators operating at energies well above the neutron binding energies of the structural materials. In these conditions from the treatment head, in the direct photon flux and from the shielded region, a fast neutron flux emerges which is partly absorbed and partly scattered by the walls, eventually establishing a nearly uniform thermal and epithermal flux in the room. Both direct and scattered flux contribute to the dose to the patient. A smaller neutron dose rate can also be found outside the treatment room, where the therapy staff works. Passive detectors, of moderation type, have been employed in the treatment room and 3He active detectors in the external zones. For the treatment room the activation data were compared with results of Monte Carlo simulation of the neutron transport in the room. Technical features of the two measures are briefly presented and results obtained around three different types of accelerators are reported. At the higher beam energies, i.e., 25 MV, a neutron dose of 0.36 Sv was estimated in the treatment field in addition to a therapeutic x-ray dose of 50 Gy. At lower energies or out of the treatment field the neutron dose drops significantly. In the external zones the dose rates everywhere are below the recommended limits and normally very low, the highest values being recorded in positions very close to the access door of the treatment room.

Vertical distribution profiles of linear alkylbenzene sulfonates and their long-chain intermediate degradation products in coastal marine sediments.

The variation with depth of the concentration of linear alkylbenzene sulfonates (LASs) and of the long-chain sulfophenyl carboxylic acids (SPCs) resulting from LAS biodegradation was determined in coastal sediments. We analyzed samples of sediment cores taken from three locations in a littoral zone subjected to the discharge of untreated urban effluents in the Bay of Cádiz in the southwestern part of the Iberian Peninsula. The vertical profile of LAS concentrations showed a sharp reduction with depth, whereas the concentration of long-chain SPCs (6-13 carbon atoms) was greatest at 10 to 14 cm depth. At this depth, the conditions in the interstitial water are strictly anoxic (Eh = -380 mV). The partition coefficients between the solid phase of the sediment versus the interstitial water are very different for LAS and for its degradation intermediates. For LAS, the organic carbon-based partition coefficient values were between 2.4 x 10(3) and 6.6 x 10(5)L/kg for the C10 and C13 homologues, respectively; these values are similar to those obtained from laboratory tests for the sorption of LAS onto marine sediments. For the long-chain SPCs, the partition coefficients are several orders of magnitude less as a consequence of their lower hydrophobicity.

Total tritium measurement in atmosphere.

Measurement of tritium in the atmosphere is of strong interest wherever this radionuclide is used. Therefore, a method is proposed for the joint measurement of burnable tritium, independently from its physico-chemical form, and of tritiated water. The method consists of transforming the tritiated molecules of the gases present in the air volume into tritiated water by burning them together with a known quantity of hydrogen. The water vapor is condensed and added to a liquid scintillator. The scintillator is also able to dissolve conventional filters so that the tritium attached to particulate and concentrated on these filters can be jointly measured, as will be discussed in a future report. The overall detection limit of the method is approximately 64 Bq m-3 for a combustion period of 10 min (which corresponds to sampling an air volume of 15 L) and a counting period of 10 min. This limit, much lower than the derived air concentrations in the most unfavorable cases, allows the application of the method for safety purposes. Moreover, the method can be integrated into a general procedure for the measurement of tritium in different chemical forms, to be applied in case of necessity.

Radiation transport in a radiotherapy room.

The photoneutron dose equivalent in a linac radiotherapy room and its entrance maze was investigated by means of Monte Carlo simulations under different conditions. Particularly, the effect of neutron absorbers and moderator layers placed on the maze walls was considered. The contribution of prompt gamma rays emitted in absorption reactions of thermal neutrons was also taken into account. The simulation results are compared with some experimental measurements in the therapy room and in the maze.

Neutron measurements in the stray field produced by 158 GeV c(-1) per nucleon lead ion beams.

This paper discusses measurements carried out at CERN in the stray radiation field produced by 158 GeV c(-1) per nucleon 208Pb82+ ions. The purpose was to test and intercompare the response of several detectors, mainly neutron measuring devices, and to determine the neutron spectral fluence as well as the microdosimetric (absorbed dose and dose equivalent) distributions in different locations around the shielding. Both active instruments and passive dosimeters were employed, including different types of Andersson-Braun rem counters, a tissue equivalent proportional counter, a set of superheated drop detectors, a Bonner sphere system, and different types of ion chambers. Activation measurements with 12C plastic scintillators and with 32S pellets were also performed to assess the neutron yield of high energy lead ions interacting with a thin gold target. The results are compared with previous measurements and with measurements made during proton runs.

A recoil-proton spectrometer based on a p-i-n diode implementing pulse-shape discrimination.

A recoil-proton spectrometer was created by coupling a p-i-n diode with a polyethylene converter. The maximum detectable energy, imposed by the thickness of the totally depleted layer, is approximately 6 MeV. The minimum detectable energy is limited by the contribution of secondary electrons generated by photons in the detector assembly. This limit is approximately 1.5 MeV at full-depletion voltage and was decreased using pulse-shape discrimination. The diode was set up in the 'reverse-injection' configuration (i.e. with the N+ layer adjacent to the converter). This configuration provides longer collection times for the electron-hole pairs generated by the recoil-protons. The pulse-shape discrimination was based on the zero-crossing time of bipolar signals from a (CR)2-(RC)2 filter. The detector was characterised using monoenergetic neutrons generated in the Van De Graaff CN accelerator at the INFN-Laboratori Nazionali di Legnaro. The energy limit for discrimination proved to be approximately 900 keV.

Synthesis and in vitro tuberculostatic activity of Co (II), Cu (II) and Ni (II) complexes of dialdehyde starch dithiosemicarbazone.

Co (II), Cu (II) and Ni (II) complexes of starch dialdehyde dithiosemicarbazone (DASTSC) of low (approximately 15%) degree of oxidation were prepared and their tuberculostatic activity was tested in vitro against isoniazid-sensitive and isoniazid-resistant strains of Mycobacterium tuberculosis. In 10-week lasting tests the DASTSC complex with Ni (II) was tuberculostatic to a similar extent as was the free ligand, whereas the Co (II) and Cu (II) complexes inhibited the growth of M. tuberculosis more efficiently. It was also proved that the corresponding non-co-ordinated metal salts were inactive to both strains of M. tuberculosis.

Antimicrobial activity of starch dialdehyde dithiosemicarbazone against Mycobacterium tuberculosis.

A dithiosemicarbazone of 13% starch dialdehyde (DASTSC) was active against Mycobacterium tuberculosis under laboratory tests. M. tuberculosis strains sensitive and resistant to isoniazid (INH) were developed at the concentrations of 2.5 x 10(-4)-5.0 x 10(-1) mg/cm3 on a solid Löwenstein-Jensen medium and treated with 1-25 mg/cm3 of DASTSC in all mutual combinations of concentrations. Both, sensitive and resistant to INH strains reacted to DASTSC. The growth of strains could be completely inhibited as proved in eight-week tests. The inhibition was non-linearly dependent on concentration of DASTSC. The lowest and the highest concentrations of DASTSC did not inhibit the M. tuberculosis growth. The doses of DASTSC were optimised.

Rapid platelet accumulation leading to thrombotic occlusion.

Platelet thrombosis under arterial conditions remains a large clinical problem. Previous in vitro experiments have concentrated on early adherence without thrombotic occlusion. We have developed a controllable hemodynamic system that creates intravascular thrombosis to occlusion. Lightly heparinized (3.5 USP units/mL), whole, porcine blood is perfused through a 1.5 mm inner diameter, tubular, collagen-coated stenosis. The microscopic growth of thrombus is optically recorded using a high resolution CCD camera. Occlusive thrombus is examined using microcomputed tomography and histology. Thrombus consistently formed in the throat of the stenosis where wall shear rates were greatest. Rapid platelet accumulation (RPA) reached rates as high as 13.7 µm(3 )µm(-2) min(-1). Total occlusion of flow occurred after 17 ± 2.6 min (n = 6). The average thrombus volume accumulation of 7.8 ± 3.5 µm(3) µm(2) min(-1) occurred under very high wall shear rates exceeding 100,000 s(-1). Significant volumes of thrombus did not form until 7.6 ± 3.6 min after the onset of flow, a delay consistent with activation of adherent mural platelets. Platelets did not accumulate with large volume for normal wall shear rates <2000 s(-1). Very high wall shear rates stimulate the capture of millions of circulating platelets with exposure times <2 ms in an arterial stenosis.