A simple but complex enough θ -SIR type model to be used with COVID-19 real data. Application to the case of Italy.

Since the start of the COVID-19 pandemic in China many models have appeared in the literature, trying to simulate its dynamics. Focusing on modeling the biological and sociological mechanisms which influence the disease spread, the basic reference example is the SIR model. However, it is too simple to be able to model those mechanisms (including the three main types of control measures: social distancing, contact tracing and health system measures) to fit real data and to simulate possible future scenarios. A question, then, arises: how much and how do we need to complexify a SIR model? We develop a θ -SEIHQRD model, which may be the simplest one satisfying the mentioned requirements for arbitrary territories and can be simplified in particular cases. We show its very good performance in the Italian case and study different future scenarios.

Modeling the impact of SARS-CoV-2 variants and vaccines on the spread of COVID-19.

The continuous mutation of SARS-CoV-2 opens the possibility of the appearance of new variants of the virus with important differences in its spreading characteristics, mortality rates, etc. On 14 December 2020, the United Kingdom reported a potentially more contagious coronavirus variant, present in that country, which is referred to as VOC 202012/01. On 18 December 2020, the South African government also announced the emergence of a new variant in a scenario similar to that of the UK, which is referred to as variant 501.V2. Another important milestone regarding this pandemic was the beginning, in December 2020, of vaccination campaigns in several countries. There are several vaccines, with different characteristics, developed by various laboratories and research centers. A natural question arises: what could be the impact of these variants and vaccines on the spread of COVID-19? Many models have been proposed to simulate the spread of COVID-19 but, to the best of our knowledge, none of them incorporates the effects of potential SARS-CoV-2 variants together with the vaccines in the spread of COVID-19. We develop here a θ - i j -SVEIHQRD mathematical model able to simulate the possible impact of this type of variants and of the vaccines, together with the main mechanisms influencing the disease spread. The model may be of interest for policy makers, as a tool to evaluate different possible future scenarios. We apply the model to the particular case of Italy (as an example of study case), showing different outcomes. We observe that the vaccines may reduce the infections, but they might not be enough for avoiding a new wave, with the current expected vaccination rates in that country, if the control measures are relaxed. Furthermore, a more contagious variant could increase significantly the cases, becoming the most common way of infection. We show how, even with the pandemic cases slowing down (with an effective reproduction number less than 1) and the disease seeming to be under control, the effective reproduction number of just the new variant may be greater than 1 and, eventually, the number of infections would increase towards a new disease wave. Therefore, a rigorous follow-up of the evolution of the number of infections with any potentially more dangerous new variant is of paramount importance at any stage of the pandemic.

New opportunities at the next-generation neutrino experiments I: BSM neutrino physics and dark matter.

The combination of the high intensity proton beam facilities and massive detectors for precision measurements of neutrino oscillation parameters including the charge-parity violating (CPV) phase will open the door to help make beyond the standard model (BSM) physics reachable even in low energy regimes in the accelerator-based experiments. Large-mass detectors with highly precise tracking and energy measurements, excellent timing resolution, and low energy thresholds will enable the searches for BSM phenomena from cosmogenic origin, as well. Therefore, it is also conceivable that BSM topics in the next-generation neutrino experiments could be the dominant physics topics in the foreseeable future, as the precision of the neutrino oscillation parameter and CPV measurements continue to improve.This paper provides a review of the current landscape of BSM theory in neutrino experiments in two selected areas of the BSM topics-dark matter and neutrino related BSM-and summarizes the current results from existing neutrino experiments to set benchmarks for both theory and experiment. This paper then provides a review of upcoming neutrino experiments throughout the next 10 to 15 year time scale and their capabilities to set the foundation for potential reach in BSM physics in the two aforementioned themes. An important outcome of this paper is to ensure theoretical and simulation tools exist to carry out studies of these new areas of physics, from the first day of the experiments, such as Deep Underground Neutrino Experiment in the U.S. and Hyper-Kamiokande Experiment in Japan.

Erratum: First Dark Matter Constraints from a SuperCDMS Single-Charge Sensitive Detector [Phys. Rev. Lett. 121, 051301 (2018)].

This corrects the article DOI: 10.1103/PhysRevLett.121.051301.

First Dark Matter Constraints from a SuperCDMS Single-Charge Sensitive Detector.

We present the first limits on inelastic electron-scattering dark matter and dark photon absorption using a prototype SuperCDMS detector having a charge resolution of 0.1 electron-hole pairs (CDMS HVeV, a 0.93 g CDMS high-voltage device). These electron-recoil limits significantly improve experimental constraints on dark matter particles with masses as low as 1 MeV/c^{2}. We demonstrate a sensitivity to dark photons competitive with other leading approaches but using substantially less exposure (0.49 g d). These results demonstrate the scientific potential of phonon-mediated semiconductor detectors that are sensitive to single electronic excitations.

Results from the Super Cryogenic Dark Matter Search Experiment at Soudan.

We report the result of a blinded search for weakly interacting massive particles (WIMPs) using the majority of the SuperCDMS Soudan data set. With an exposure of 1690 kg d, a single candidate event is observed, consistent with expected backgrounds. This analysis (combined with previous Ge results) sets an upper limit on the spin-independent WIMP-nucleon cross section of 1.4×10^{-44} (1.0×10^{-44}) cm^{2} at 46 GeV/c^{2}. These results set the strongest limits for WIMP-germanium-nucleus interactions for masses >12 GeV/c^{2}.

Dominant position of colorectal cancer in Slovakia: the old-new problem for cancer control.

The development of colorectal cancer in former Czechoslovakia and its successor states is illustrated using recorded mortality and from 1968 incidence rates retrieved from National Cancer Registry of Slovakia. The relatively high mortality rates in Czechoslovakia around 1950 contrasted with rates seen in other countries of central, southern and particularly of eastern Europe and were more close to those recorded in affluent countries of western Europe and northern America. Despite continuous stabilisation and decrease of this cancer in high risk countries from late 1970s the unexpected and gradual rise of incidence rates of colorectal cancer was recorded in Slovakia. During the period studied incidence rates rose by an annual mean percent change of 4,2 and 2,8 in colon and 2,2 and 1,0 in rectal cancer in males and females respectively. Beginning with the year 1995 colorectal cancer is the most common cancer in this country in both genders together. Study of the development of colorectal cancer at the levels of subsites indicated the higher rates but decreasing proportion of rectal cancer and increasing proportion of cases occurring in proximal colon. The importance of this new priority in diagnostics, treatment and control programmes is stressed.

A case-control study of lifestyle and lung cancer associations by histological types.

The objective of the study was to investigate the contribution of dietary factors and physical exercise to the variation in the risk of lung cancer and its major histological types among men and women in the Czech Republic, and reveal interactions between smoking and diet/physical exercise, if any. In a hospital based case-control study, data collected by in-person interviews from 1096 microscopically confirmed lung cancer cases (587 women, 509 men) and 2966 controls were analyzed using unconditional logistic regression stratified by appropriate factors. Among all nonsmoking women protective effects were observed for black tea (OR=0.69), among all smoking women for wine (OR=0.71), physical exercise (OR=0.64) and vitamin supplements (OR=0.71). Among all men, inverse associations were found in smokers between lung cancer risk and frequent intake of fruits (OR=0.69) or moderate intake of spirits (OR=0.64), and a direct association for fat foods (OR=1.68). Comparing the effects of diet/physical activity on lung cancer risk among nonsmokers versus smokers, interactions with smoking appeared for the intake of black tea and milk/dairy products among women, and for moderate intake of spirits in men. When the effects of diet/physical exercise on risk were analyzed by major cell types in women, the intake of wine and physical exercise were inversely associated with the risk of both adenocarcinoma and small cell cancer, the intakes of fruits and vitamin supplements were inversely associated with the risk of squamous cell cancer. In men, the intake of fat foods was directly associated with the risk of squamous cell cancer, while the frequent intake of apples was inversely associated with the risk of both squamous- and small cell cancers. In men an inverse association with the risk of squamous cell cancer was found for the intake of other fruits. These data suggest that diet/physical exercise may affect the risk of lung cancer and major cell types, and that interactions between some dietary items and smoking may occur. Lung cancer is a multifactorial disease, since smoking, its main determinant, and other environmental and lifestyle factors interact with one another and with genetic factors to cause the disease.

Interactions between smoking and other exposures associated with lung cancer risk in women: diet and physical activity.

UNLABELLED: The objective of the study is to estimate the differences in the impact of diet and physical exercise on lung cancer risk in female nonsmokers vs. smokers, and reveal interactions, if any. In a hospital based case-control study, data collected by in-person interviews from 569 female lung cancer cases and 2120 controls were analyzed using unconditional logistic regression stratifying by appropriate factors. Protective effects were observed for intake of milk/dairy products (OR=0.57, 95%CI 0.35-0.94), vegetables (OR=0.60, 95%CI 0.40-0.91), apples (OR=0.69), wine (OR=0.77), and physical exercise (OR=0.59, 95%CI 0.42-0.83) among smokers only, while no similar effects were found among nonsmokers. In contrast, the intake of black tea was associated with a protective effect (OR=0.66, 95%CI 0.47-0.94) among nonsmokers only. Comparing the effects of dietary items and physical activity on lung cancer risk among nonsmokers versus smokers, statistically significant effect modifications were found for black tea (P 0.005), and milk/dairy products (P 0.047). Borderline effect modifications emerged for physical exercise (P 0.077). CONCLUSIONS: These results indicate protective effects of some components of healthful diet and physical exercise among smokers, and of the intake of black tea among nonsmokers. The observed interactions of the impact of black tea, milk/dairy products and physical activity upon lung cancer risk in women at different levels of the smoking habit deserve further studies.

Immunoregulatory properties of synthetic peptides, fragments of a proline-rich polypeptide (PRP) from ovine colostrum.

It has been previously found that a proline-rich polypeptide (PRP) isolated from ovine colostrum has a regulatory effect on the immune response. A nonapeptide fragment Val-Glu-Ser-Tyr-Val-Pro-Leu-Phe-Pro was isolated from the chymotryptic digest of PRP. The nonapeptide showed biological activity similar to PRP. The determined amino acid sequence was now confirmed by synthesis. Synthetic nonapeptide as well as its C-terminal hexapeptide, Tyr-Val-Pro-Leu-Phe-Pro, showed biological activity similar to PRP and the nonapeptide obtained from PRP.

Immunoregulatory activity of substance P fragments.

The C-terminal SP7-11 pentapeptide (Phe-Phe-Gly-Leu-Met-NH2) was found to suppress in vitro the immune response in a dose of 1-5 micrograms/ml. It produced also a distinct immunosuppression in vivo, by both per os and intraperitoneal, applications. In contrast, the N-terminal SP1-4 fragment (Arg-Pro-Lys-Pro) suppressed the response at a dose of 0.1 microgram/ml, but stimulated it slightly at higher doses (1-5 micrograms/ml). A structural analog of SP1-4 (Gly-Pro-Arg-Pro tetrapeptide) was found to be a strong immunosuppressor at a dose of 5 micrograms/ml, indicating the importance of N-terminal basic residue for the immunoregulatory activity of intact SP.

A case-control study of lung cancer among Czech women.

Few data are available to explain the continuing increase in lung cancer mortality among Czech women. The study was designed to examine the role of active smoking and other known or suspected factors. Data collected by personal interviews during the 15 months of a hospital-based case control study are reported. A total of 140 microscopically confirmed cases and 280 frequency-matched controls were analysed using multiple logistic regression. Cigarette smoking was the most important factor associated with excess risk for lung cancer among women. Significantly increased risk was found both among current smokers (OR=11.20, 95% CI 5.9-21.2), and ex-smokers (OR=10.02, 95% CI 5.5-18.4). Positive dose-response gradients (P<0.001) were observed between lung cancer risk and the daily number of cigarettes, duration of smoking, number of pack-years, inhaling, and grade of nicotine dependence assessed by the Fagerström test (Heatherton TF, Kozlowski LT, Frecker RC, Fagerström KO. Br J Addict 1991;86:1119-1470; Pomerleau OF. In: Bolliger CT, Fagerström KO, editors. The Tobacco Epidemic. Basle: Karger, 1997: 122-131). Exposure to environmental smoke was associated with elevated lung cancer risk (OR=3.58, for lifetime non-smokers exposed both in childhood and in adult age). Physical exercise and body mass index were inversely associated with lung cancer risk. For the category of physical exercise of more than 5 h per week, the odds ratio was 0.38, compared to subjects admitting no physical exercise. For body mass index, the odds ratio for the highest (compared to the lowest) quartile was 0.50. Chronic cough and phlegm (at least 3 months per year) were associated with excess risk (OR=6.07) only if their duration was less than 2 years before diagnosis of lung cancer, and, therefore, they were suspected of being more likely early symptoms of preclinical lung cancer rather than its cause. Our results support the statement that cigarette smoking is by far the most important cause of the on-going epidemic of lung cancer among Czech women, and are consistent with the concept of a balance between risk and protective factors whose eventual maintenance or alteration determine the development of disease (as suggested by Rylander R, Axelsson G, Andersson L, Liljequist T, Bergman B. Lung Cancer 1996;14(Suppl 1): S75-S83). Concerted control of smoking appears to be an urgent priority in lung cancer prevention among women, including specific approaches targeted on the female population.

Statistical modelling and prediction of lung cancer mortality in the Czech and Slovak Republics, 1960-1999.

BACKGROUND: The aim of the study was to analyse the pattern of lung cancer mortality from 1960 to 1989 and to predict lung cancer mortality for 1990-1999 for males and females aged > or = 30 years in the Czech and Slovak Republics. METHOD: The mortality pattern of lung cancer was examined and predicted using republic-age-period-cohort models. RESULTS: Trends in lung cancer mortality were upward for both sexes over the study period. In the early 1960s, lung cancer mortality in Slovak males was much lower than that in Czech males, but since the late 1960s lung cancer mortality in males increased more rapidly in Slovakia than in the Czech Republic. It was predicted that mortality due to lung cancer in Slovak males would exceed that in Czech males during the last 5 years of the 20th century. Slovak female lung cancer mortality was lower than that for Czech females throughout the study period, and the trends in both republics were similar.

New analogs of the immunoregulatory PRP-pentapeptide.

To determine the role of consecutive amino acid residues in the immunoreactivity of the shortest active fragment of PRP, a series of analogs substituted by L-alanine in successive positions of the peptide chain was synthesized. The immunological investigations were carried out in several models: the immune response to T-cell dependent antigen, SRBC (in vivo and in vitro) and to T-cell independent antigen, PVP in vitro. The immunotropic action of the peptide was, in addition, verified with respect to thymocytes forming autologous rosettes. The results of these experiments revealed immunotropic activity (in all tests) of the analog containing alanine instead of proline in position 5 of PRP-pentapeptide.

Regional and national variation in lung cancer mortality in Italy and Czechoslovakia.

In developed countries lung cancer mortality has been shown to be related to lifestyle, occupational and environmental aspects, diet, and other factors which may vary widely from one region to another. To investigate inter-area differences in lung cancer mortality and cigarette smoking a descriptive study has been carried out in three areas of Italy and two republics of Czechoslovakia. The highest death rates from lung cancer were found in the Czech Republic and Northern Italy, for both sexes. Analysis of age-specific rates by birth cohort, comparing all five areas, showed the greatest differences in trends between Slovakia and Northern Italy in men, and between the Czech Republic and Southern Italy in women. The lowest rates were observed in Southern Italy throughout the period under study, particularly among women. Making allowance for the latency period between the onset of exposure and the development of the disease, data on the occurrence of lung cancer could be interpreted looking at previous smoking habits. An imperfect overlap between the trend of cigarette smoking and the corresponding lung cancer mortality pattern was present in Northern and Southern Italy, a finding suggesting that even non-smoking-related factors could have played a significant role in lung cancer aetiology.

Dietary habits and lung cancer risk among non-smoking women.

A case-control study was conducted to investigate the relationship between diet and the risk of lung cancer among women non-smokers and to compare with women smokers in the same population. Data collected by personal interviews from 435 microscopically confirmed cases and 1710 controls were analysed using unconditional logistic regression. In addition to results for all study subjects, associations between diet and lung cancer risk were compared between two highly contrasting groups: smokers (odds ratio (OR) 7.03) and non-smokers (OR 1.00). A protective effect of frequent (daily or several times per week) black tea drinking appeared among non-smoking women (OR 0.65, 95% confidence interval (CI) 0.43-0.99). Among smoking women, protective effects were observed for frequent intake of milk/dairy products (OR 0.56, 95% CI 0.32-0.96), coffee (OR 0.47, 95% CI 0.25-0.88), and wine consumption (daily or weekly OR 0.60, 95% CI 0.37-0.98; monthly OR 0.60, 95% CI 0.39-0.94). Inverse associations with the risk appeared for physical exercise for smokers only, and for the body mass index both among non-smoking and smoking women. Some items of diet may contribute to variation in risk among women in the Czech Republic; their importance seems to vary in relation to their status in smoking, the dominant factor in the aetiology of lung cancer.

Characterization of phospholipase A2 secretion from human platelets.

Human platelets secreted phospholipase A2 in a dose- and time-dependent manner when challenged with thrombin, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), or collagen. Enzyme release was maximal at concentrations of 0.1 units/ml of thrombin, 100 nM TPA, or 2 micrograms/ml of collagen; and complete by 2 min in platelets treated with thrombin or TPA. Cells challenged with collagen required up to 5 min for maximal secretion. Besides dose and time functions, phospholipase A2 secretion was also dependent on platelet concentration and the levels of bovine serum albumin in the incubation medium. The secreted enzyme was soluble and exhibited substrate and Ca2+ requirements similar to a detergent-solubilized, partially purified phospholipase A2 from whole platelets [Kramer et al., Biochim. Biophys. Acta (1988) 959, 269-279]. The pH optimum of the secreted enzyme, however, was 1-2 units lower than the pH optimum of the phospholipase A2 from whole cells. Secreted phospholipase A2 hydrolyzed phosphatidylethanolamine at 5-12 times the rate of phosphatidylcholine when the substrates were present in pure form. These apparent differences in activity were greatly diminished, though, when 1:1 molar mixtures of the two substrates were employed. Because phospholipase A2 catalyzes a key reaction during the formation of bioactive arachidonate metabolites, the secretion of this enzyme from platelets may be important in the regulation of thrombosis.

Effect of tuftsin and its partial sequences on the arterial blood pressure in guinea-pigs.

The effect of tuftsin (Thr-Lys-Pro-Arg) and its partial sequences: Thr-Lys-Pro, Lys-Pro-Arg, Thr-Lys, Lys-Pro and Pro-Arg on arterial blood pressure was studied in experiments on guinea-pigs anesthetized with urethane. The peptides were administered intravenously in a dose of 1 mg/kg. The blood pressure was measured directly in the carotid artery. Tuftsin and peptides: Thr-Lys-Pro, Thr-Lys and Pro-Arg, after longer period of latency, caused protracted rise in arterial blood pressure. Such action was not shown by Lys-Pro-Arg and Lys-Pro.

Immunosuppressive activity of C-terminal fragments of tachykinins.

The immunosuppressive activity of three pentapeptides related to the C-terminal fragments of tachykinins was investigated using the PFC (plaque forming cell) test. The peptides were of the general structure Phe-X-Gly-Leu-Met-NH2, with Tyr, Val and Ile in X position, respectively. The results were compared with those obtained previously for the substance P (SP) C-terminal pentapeptide. It was found that peptides containing aromatic residues in X position were more potent immunosuppressors than peptides containing aliphatic residues in the same position. The results also suggest that in mammalian organisms substance SP may be involved in immunomodulation which is rather not the case with other mammalian tachykinins (neurokinin A and neurokinin B).

The absolute configuration on the chiral nitrogen atom of proline residue in the metal complexes of oligopeptides.

The CD spectra of the Cu(II) and Ni(II) complexes with peptides containing N-terminal L-proline residue are discussed. The formation of the absolute configuration on the bound proline nitrogen is observed in all studied complexes and its contribution to the chiralooptical properties is easily seen in CD spectra.