On the possibility to search for double beta decay of initially unstable (alpha/beta radioactive) nuclei

Possibilities to search for double beta decay of alpha/beta unstable nuclei, many of which have higher energy release than "conventional" (beta stable) double beta decay candidates, are discussed. First experimental half-life limits on double beta decay of radioactive nuclides from U and Th families (trace contaminants of the CaWO_4, CdWO_4 and Gd_2SiO_5 scintillators) were established by reanalyzing the data of low-background measurements in the Solotvina Underground Laboratory with these detectors (1734 h with CaWO_4, 13316 h with CdWO_4, and 13949 h with Gd_2SiO_5 crystals).Comment: 15 pages, 6 figure

Quest for double beta decay of 160-Gd and Ce isotopes

The double beta decay study of 160-Gd has been performed in the Solotvina Underground Laboratory with the help of Gd_2SiO_5(Ce) crystal scintillator (volume 95 cc). The background of the detector in the vicinity of the 2 beta energy of 160-Gd was reduced to 1.0 cpd/keV kg. The new improved half-life limits have been established for neutrinoless 2 beta decay of 160-Gd to the ground and first excited levels of 160-Dy: T1/2 > 2.3(1.3)E21 yr at 68%(90%) C.L. The T1/2 bounds have been also set for two neutrino mode as well as for 2 beta decay with Majorons emission. Also the limits were established for different 2 beta decay processes in 136-Ce, 138-Ce and 142-Ce.Comment: 12 pages, 6 figures, submitted to Nucl. Phys.

Factors influencing the efficacy of praziquantel in a schistosome-exposed population

Urogenital schistosomiasis, caused by the Schistosoma haematobium parasite, is a global cause of morbidity and mortality and affects millions of people each year. The mass drug administration (MDA) of praziquantel (PZQ) is a vital intervention to treat schistosome infections and eliminate schistosomiasis as a public health problem. After decades of use, variable PZQ efficacy and persistent schistosome infections have been reported across multiple schistosome-endemic African countries. However, there is a paucity of information on the factors that influence the efficacy of a PZQ treatment and contribute to the persistence of infection, particularly in schistosome-exposed populations where the drug is commonly used. To address this, I examined the factors that influence individual responses to PZQ and how these contribute to variable PZQ efficacy. This focused on alterations to PZQ metabolism, which regulates the concentration of the schistosome-killing PZQ, and thus can be a crucial determinant of PZQ efficacy and adverse drug reactions (ADRs). During a review of published studies, I identified several drug and host-related factors, such as drug-drug interactions (DDIs) and the liver’s capacity to metabolise PZQ, that influenced the systemic concentrations of PZQ via altered PZQ metabolism, and discussed the resultant impact on PZQ efficacy. This review also highlighted gaps in the research regarding pharmacogenetic (PGx) and metabolomic studies. Consequently, I characterised PGx variations in PZQ- metabolising cytochrome P450 (CYP) enzymes and determined associations between each detected variant and the efficacy of PZQ treatment in S. haematobium-infected Zimbabweans. Four single nucleotide polymorphisms (SNPs) across the CYP1A2, CYP2D6 and CYP3A5 enzymes were significantly associated with PZQ treatment outcome, including genotypes that increased the odds of an individual clearing or not clearing schistosome infection. A further study using in vivo analyte concentrations detected no associations with PZQ efficacy. Yet, there were significant associations between variants in the CYP1A2 and CYP2C9 enzymes and in vivo analyte concentrations indicative of increased metabolism and decreased PZQ exposure. Both PGx studies provided insight into the drug-gene interactions in schistosome-infected patients during a PZQ treatment and suggested that the PGx impact on PZQ exposure and efficacy may be underestimated in the diverse African populations where PZQ is utilised. To determine if variable PZQ efficacy and persistent schistosome infections occurred during MDAs in Zimbabwe, I identified persistent hotspots of S. haematobium infection prevalence (PPHS) and hotspots of decreasing efficacy of PZQ (EPHS). Further, the risk factors of hotspot emergence were evaluated, and EPHS were not identified as a primary cause for PPHS based on these analyses. Initial infection intensity was significantly higher in PPHS than in responder districts, providing valuable information on the possibility of early identification of persistent schistosome infections to improve on current control strategies. However, there was no clear predictor of EPHS occurrence. Overall, this thesis highlighted key factors that influence an individual’s response to a PZQ treatment, including multiple PGx determinants which were previously underreported. Together, this thesis produced significant novel data towards the characterisation of the host factors that contribute towards variable PZQ efficacy, and in the identification of hotspots of persistent infections. Together, these findings will inform policymakers on the factors that influence PZQ efficacy to improve schistosomiasis control and eliminate this disease

High sensitivity double beta decay study of 116-Cd and 100-Mo with the BOREXINO Counting Test Facility (CAMEO project)

The unique features (super-low background and large sensitive volume) of the CTF and BOREXINO set ups are used in the CAMEO project for a high sensitivity study of 100-Mo and 116-Cd neutrinoless double beta decay. Pilot measurements with 116-Cd and Monte Carlo simulations show that the sensitivity of the CAMEO experiment (in terms of the half-life limit for neutrinoless double beta decay) is (3-5) 10^24 yr with a 1 kg source of 100-Mo (116-Cd, 82-Se, and 150-Nd) and about 10^26 yr with 65 kg of enriched 116-CdWO_4 crystals placed in the liquid scintillator of the CTF. The last value corresponds to a limit on the neutrino mass of less than 0.06 eV. Similarly with 1000 kg of 116-CdWO_4 crystals located in the BOREXINO apparatus the neutrino mass limit can be pushed down to m_nu<0.02 eV.Comment: 29 pages, LaTex, 9 eps figure

New limits on di-nucleons decay into invisible channels

Data of the radiochemical experiment [E.L.Fireman, 1978] with 1.7 t of KC_2H_3O_2, accumulated deep underground during ~1 yr, were reanalyzed to set limits on di-nucleons (nn and np) decays into invisible channels (disappearance, decay into neutrinos, etc.). The obtained lifetime bounds tau_np > 2.1 10^25 yr and tau_nn > 4.2 10^25 yr (at 90% C.L.) are better (or competitive) than those established in the recent experiments.Comment: 3 pages, accepted in JETP Letter

DYNAMICS OF FORMATION AND DEVELOPMENT OF DEPRESSIVE AND COGNITIVE DISORDERS IN PATIENTS AFTER CEREBRAL STROKE

Features of clinical structure, regularities of formation, development and course of depressive and cognitive disorders in patients after cerebral stroke were determined. In patients with cerebral stroke the disorder of state of consciousness with cognitive and asthenic disorders with further formation of psychoemotional disorders with elements of hypochondria on the background of remaining cognitive disorders are primary

Drug metabolism and pharmacokinetics of praziquantel:A review of variable drug exposure during schistosomiasis treatment in human hosts and experimental models

Schistosomiasis control is heavily reliant on the drug praziquantel (PZQ), which is used as preventive chemotherapy as part of national helminth control strategies. Given the heavy reliance on PZQ for mass drug administration, there has been considerable research on the potential of parasites developing resistance to the drug, resulting in decreased drug efficacy. However, there have been comparatively fewer studies of other factors that can potentially alter PZQ efficacy. Here, we investigate whether host PZQ metabolism contributes towards variable cure rates. We evaluate factors that can influence the metabolism of PZQ and the resultant effect on the efficacy of PZQ treatment to determine factors that potentially influence an individual's response to the drug. The literature search was directed at published studies from three online databases: Web of Science, PubMed, and EMBASE. The search terms for the review comprised of ([praziquantel OR PZQ] AND [schistosom* OR bilharzia] AND [pharmaco*]) and included studies evaluating PZQ metabolism. Publications were categorised into pharmacokinetics, drug-drug interactions, pharmacogenetics, and metabolite analysis. Forty publications describing human and experimental studies fitted the inclusion criteria and were subjected to data extraction and analysis. The analyses showed that variable exposure to PZQ was associated with alterations in the liver's capacity to metabolise PZQ and observed drug-drug interactions. Other factors influencing the efficacy of PZQ were brand, formulation, and co-administered food. Although some work has been performed on metabolite identification, there was minimal information on PZQ's metabolic pathway, and no pharmacogenetics studies were identified. The study indicated that in both human and experimental studies alterations in the liver's capacity to metabolise PZQ as well as drug-drug interactions affected systemic levels of PZQ that could result in variable cure rates. The study confirmed previous findings of higher antischistosomal activity of (R)-PZQ enantiomer when administered alone compared to the racemate at the same dose as well as improved efficacy when the drug is administered with food. The study also highlighted the need for more comprehensive studies of the PZQ metabolic pathway and PZQ pharmacogenetic studies in humans

Experimental limits on the proton life-time from the neutrino experiments with heavy water

Experimental data on the number of neutrons born in the heavy water targets of the large neutrino detectors are used to set the limit on the proton life-time independently on decay mode through the reaction d -> n+?. The best up-to-date limit tau_p > 4 10^23 yr with 95% C.L. is derived from the measurements with D_2O target (mass 267 kg) installed near the Bugey reactor. This value can be improved by six orders of magnitude with future data accumulated with the SNO detector containing 1000 t of D_2O.Comment: LaTeX, 7 pages, 1 table; small typo is correcte

Applications of High Resolution High Sensitivity Observations of the CMB

With WMAP putting the phenomenological standard model of cosmology on a strong footing, one can look forward to mining the cosmic microwave background (CMB) for fundamental physics with higher sensitivity and on smaller scales. Future CMB observations have the potential to measure absolute neutrino masses, test for cosmic acceleration independent of supernova Ia observations, probe for the presence of dark energy at redshifts of 2 and larger, illuminate the end of the dark ages, measure the scale--dependence of the primordial power spectrum and detect gravitational waves generated by inflation.Comment: To be published in the proceedings of the workshop on "The Cosmic Microwave Background and its Polarization", New Astronomy Reviews, (eds. S. Hanany and K.A. Olive