Early diagnosis of pancreatic cancer: What strategies to avoid a foretold catastrophe

While great strides in improving survival rates have been made for most cancers in recent years, pancreatic ductal adenocarcinoma (PDAC) remains one of the solid tumors with the worst prognosis. PDAC mortality often overlaps with incidence. Surgical resection is the only potentially curative treatment, but it can be performed in a very limited number of cases. In order to improve the prognosis of PDAC, there are ideally two possible ways: the discovery of new strategies or drugs that will make it possible to treat the tumor more successfully or an earlier diagnosis that will allow patients to be operated on at a less advanced stage. The aim of this review was to summarize all the possible strategies available today for the early diagnosis of PDAC and the paths that research needs to take to make this goal ever closer. All the most recent studies on risk factors and screening modalities, new laboratory tests including liquid biopsy, new imaging methods and possible applications of artificial intelligence and machine learning were reviewed and commented on. Unfortunately, in 2022 the results for this type of cancer still remain discouraging, while a catastrophic increase in cases is expected in the coming years. The article was also written with the aim of highlighting the urgency of devoting more attention and resources to this pathology in order to reach a solution that seems more and more unreachable every day

Ritz-like values in steplength selections for stochastic gradient methods

The steplength selection is a crucial issue for the effectiveness of the stochastic gradient methods for large-scale optimization problems arising in machine learning. In a recent paper, Bollapragada et al. (SIAM J Optim 28(4):3312–3343, 2018) propose to include an adaptive subsampling strategy into a stochastic gradient scheme, with the aim to assure the descent feature in expectation of the stochastic gradient directions. In this approach, theoretical convergence properties are preserved under the assumption that the positive steplength satisfies at any iteration a suitable bound depending on the inverse of the Lipschitz constant of the objective function gradient. In this paper, we propose to tailor for the stochastic gradient scheme the steplength selection adopted in the full-gradient method knows as limited memory steepest descent method. This strategy, based on the Ritz-like values of a suitable matrix, enables to give a local estimate of the inverse of the local Lipschitz parameter, without introducing line search techniques, while the possible increase in the size of the subsample used to compute the stochastic gradient enables to control the variance of this direction. An extensive numerical experimentation highlights that the new rule makes the tuning of the parameters less expensive than the trial procedure for the efficient selection of a constant step in standard and mini-batch stochastic gradient methods

Behavioural Evidence and Chemical Identification of a Female Sex Pheromone in Anagrus atomus (Hymenoptera: Mymaridae)

Anagrus atomus (L.) is an egg parasitoid involved in the biological control of Empoasca vitis (G\uf6the) in vineyards. Sex pheromones play a crucial role in mate finding for several parasitoid species and could be used for monitoring under field conditions. We carried out laboratory and field studies aimed at assessing the existence and identity of a possible A. atomus sex pheromone. We found that males were significantly attracted by virgin females independent of age. Males were not attracted to individuals of the same sex, but they were attracted by a crude extract from an unmated female and its polar fraction. Eugenol (4-allyl-2-methoxyphenol) was identified as the attractive substance and proved to be attractive not only in the olfactometer but also in another laboratory bioassay and under field conditions. Attraction of males, but not females, confirms that this is not an aggregation pheromone. This is the first sex-pheromone component identified in Mymaridae, however more compounds could be involved in the mating behaviour of A. atomus. The utility of a sex pheromone in A. atomus is discussed in the context of fitness returns

The evolution of the large-scale emission in FRI jets

Recent observations in X-rays and gamma-rays of nearby FRI radio galaxies have raised the question of the origin of the emission detected in the termination structures of their jets. The study of these structures can give information on the conditions for particle acceleration and radiation at the front shocks. In addition, an evolutionary scenario can help to disentangle the origin of the detected X-ray emission in young FRI sources, like some Gigahertz Peaked Spectrum AGNs. This work focuses on the nature and detectability of the radiation seen from the termination regions of evolving FRI jets. We use the results of a relativistic, two-dimensional numerical simulation of the propagation of an FRI jet, coupled with a radiation model, to make predictions for the spectra and lightcurves of the thermal and non-thermal emission at different stages of the FRI evolution. Our results show that under moderate magnetic fields, the synchrotron radiation would be the dominant non-thermal channel, appearing extended in radio and more compact in X-rays, with relatively small flux variations with time. The shocked jet synchrotron emission would dominate the X-ray band, although the shocked ISM/ICM thermal component alone may be significant in old sources. Inverse Compton scattering of CMB photons could yield significant fluxes in the GeV and TeV bands, with a non-negligible X-ray contribution. The IC radiation would present a bigger angular size in X-rays and GeV than in TeV, with fluxes increasing with time. We conclude that the thermal and non-thermal broadband emission from the termination regions of FRI jets could be detectable for sources located up to distances of a few 100 Mpc.Comment: 9 pages, 5 figures, accepted for publication in MNRA

Swimming at the Time of COVID-19: A Cross-Sectional Study among Young Italian Competitive Athletes

During the coronavirus disease 2019 (COVID-19) pandemic, several restriction measures were imposed to control the virus transmission, with important repercussions on different sectors, including sport. This study aimed to explore the effects of the COVID-19 pandemic on Italian competitive swimmers by analyzing how the disease and the restriction measures affected their training. In total, 396 competitive swimmers (mean age 16.0 ± 3.2 years) participated. A questionnaire was used to collect their general information, to assess whether they had had COVID-19 and the number of training days lost due to the disease or to the closure of swimming facilities, and the possible alternative training adopted. Twenty-four (6.1%) participants had had COVID-19 and lost, on average, 32 training days. The closure of facilities caused an interruption in swimming training for about 18% of the participants. The majority of these continued their training, mainly through home-based exercise, but reduced their weekly training time (-8 median hours/week). A positive association was found between regularly adopted weekly training volume and that assumed during pandemic closure (OR 9.433, CI95% 1.644–54.137, p = 0.012), suggesting that the previous level of engagement in sport can represent a predictor of exercise maintenance in challenging situations such as a pandemic. Further studies are needed to identify personal, environmental, and social resources that can help individuals to counteract the negative effects of restriction measures

Velocity asymmetries in YSO jets: Intrinsic and extrinsic mechanisms

It is a well established fact that some YSO jets (e.g. RW Aur) display different propagation speeds between their blue and red shifted parts, a feature possibly associated with the central engine or the environment in which the jet propagates. In order to understand the origin of asymmetric YSO jet velocities, we investigate the efficiency of two candidate mechanisms, one based on the intrinsic properties of the system and one based on the role of the external medium. In particular, a parallel or anti-parallel configuration between the protostellar magnetosphere and the disk magnetic field is considered and the resulting dynamics are examined both in an ideal and a resistive magneto-hydrodynamical (MHD) regime. Moreover, we explore the effects of a potential difference in the pressure of the environment, as a consequence of the non-uniform density distribution of molecular clouds. Ideal and resistive axisymmetric numerical simulations are carried out for a variety of models, all of which are based on a combination of two analytical solutions, a disk wind and a stellar outflow. We find that jet velocity asymmetries can indeed occur both when multipolar magnetic moments are present in the star-disk system as well as when non-uniform environments are considered. The latter case is an external mechanism that can easily explain the large time scale of the phenomenon, whereas the former one naturally relates it to the YSO intrinsic properties. [abridged]Comment: accepted for publication in A&

A novel kcna2 variant in a patient with non-progressive congenital ataxia and epilepsy: Functional characterization and sensitivity to 4-aminopyridine

Kv1.2 channels, encoded by the KCNA2 gene, are localized in the central and peripheral nervous system, where they regulate neuronal excitability. Recently, heterozygous mutations in KCNA2 have been associated with a spectrum of symptoms extending from epileptic encephalopathy, intellectual disability, and cerebellar ataxia. Patients are treated with a combination of antiepileptic drugs and 4-aminopyridine (4-AP) has been recently trialed in specific cases. We identified a novel variant in KCNA2, E236K, in a Serbian proband with non-progressive congenital ataxia and early onset epilepsy, treated with sodium valproate. To ascertain the pathogenicity of E236K mutation and to verify its sensitivity to 4-AP, we transfected HEK 293 cells with Kv1.2 WT or E236K cDNAs and recorded potassium currents through the whole-cell patchclamp. In silico analysis supported the electrophysiological data. E236K channels showed voltagedependent activation shifted towards negative potentials and slower kinetics of deactivation and activation compared with Kv1.2 WT. Heteromeric Kv1.2 WT+E236K channels, resembling the condition of the heterozygous patient, confirmed a mixed gain-and loss-of-function (GoF/LoF) biophysical phenotype. 4-AP inhibited both Kv1.2 and E236K channels with similar potency. Homology modeling studies of mutant channels suggested a reduced interaction between the residue K236 in the S2 segment and the gating charges at S4. Overall, the biophysical phenotype of E236K channels correlates with the mild end of the clinical spectrum reported in patients with GoF/LoF defects. The response to 4-AP corroborates existing evidence that KCNA2-disorders could benefit from variant-tailored therapeutic approaches, based on functional studies

On the global hydration kinetics of tricalcium silicate cement

We reconsider a number of measurements for the overall hydration kinetics of tricalcium silicate pastes having an initial water to cement weight ratio close to 0.5. We find that the time dependent ratio of hydrated and unhydrated silica mole numbers can be well characterized by two power-laws in time, $x/(1-x)\sim (t/t_x)^\psi$. For early times $t < t_x$ we find an `accelerated' hydration ($\psi = 5/2$) and for later times $t > t_x$ a `deaccelerated' behavior ($\psi = 1/2$). The crossover time is estimated as $t_x \approx 16 hours$. We interpret these results in terms of a global second order rate equation indicating that (a) hydrates catalyse the hydration process for $t<t_x$, (b) they inhibit further hydration for $t > t_x$ and (c) the value of the associated second order rate constant is of magnitude 6x10^{-7} - 7x10^{-6} liter mol^{-1} s^{-1}. We argue, by considering the hydration process actually being furnished as a diffusion limited precipitation that the exponents $\psi = 5/2$ and $\psi = 1/2$ directly indicate a preferentially `plate' like hydrate microstructure. This is essentially in agreement with experimental observations of cellular hydrate microstructures for this class of materials.Comment: RevTeX macros, 6 pages, 4 postscript figure

Two-Dimensional Spectroscopy of Extended Molecular Systems: Applications to Energy Transport and Relaxation in an α-Helix

A simulation study of the coupled dynamics of amide I and amide II vibrations in an α-helix dissolved in water shows that two-dimensional (2D) infrared spectroscopy may be used to disentangle the energy transport along the helix through each of these modes from the energy relaxation between them. Time scales for both types of processes are obtained. Using polarization-dependent 2D spectroscopy is an important ingredient in the method we propose. The method may also be applied to other two-band systems, both in the infrared (collective vibrations) and the visible (excitons) parts of the spectrum.

Increased prevalence of clonal hematopoiesis of indeterminate potential amongst people living with HIV

People living with human immunodeficiency virus (PLWH) have significantly increased risk for cardiovascular disease in part due to inflammation and immune dysregulation. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related acquisition and expansion of hematopoietic stem cells due to leukemogenic driver mutations, increases risk for both hematologic malignancy and coronary artery disease (CAD). Since increased inflammation is hypothesized to be both a cause and consequence of CHIP, we hypothesized that PLWH have a greater prevalence of CHIP. We searched for CHIP in multi-ethnic cases from the Swiss HIV Cohort Study (SHCS, n = 600) and controls from the Atherosclerosis Risk in the Communities study (ARIC, n = 8111) from blood DNA-derived exome sequences. We observed that HIV is associated with a twofold increase in CHIP prevalence, both in the whole study population and in a subset of 230 cases and 1002 matched controls selected by propensity matching to control for demographic imbalances (SHCS 7%, ARIC 3%, p = 0.005). We also observed that ASXL1 is the most commonly mutated CHIP-associated gene in PLWH. Our results suggest that CHIP may contribute to the excess cardiovascular risk observed in PLWH