The benefits of exercise training for cancer patients are becoming increasingly evident. Physical exercise has been shown to reduce cancer incidence and inhibit tumor growth. Here we provide the ...status of the current molecular understanding of the effect of exercise on cancer. We propose that exercise has a role in controlling cancer progression through a direct effect on tumor-intrinsic factors, interplay with whole-body exercise effects, alleviation of cancer-related adverse events, and improvement of anti-cancer treatment efficacy. These findings have wide-ranging societal implications, as this understanding may lead to changes in cancer treatment strategies.
Hojman et al. discuss the role of exercise in controlling cancer progression through direct effects on tumor-intrinsic factors, interplay with whole-body exercise effects, alleviation of cancer-related adverse events, and improvement of cancer treatment efficacy. Understanding these mechanistic interactions is warranted for pursuing exercise as cancer medicine.
Non-additive genetic variation is usually ignored when genome-wide markers are used to study the genetic architecture and genomic prediction of complex traits in human, wild life, model organisms or ...farm animals. However, non-additive genetic effects may have an important contribution to total genetic variation of complex traits. This study presented a genomic BLUP model including additive and non-additive genetic effects, in which additive and non-additive genetic relation matrices were constructed from information of genome-wide dense single nucleotide polymorphism (SNP) markers. In addition, this study for the first time proposed a method to construct dominance relationship matrix using SNP markers and demonstrated it in detail. The proposed model was implemented to investigate the amounts of additive genetic, dominance and epistatic variations, and assessed the accuracy and unbiasedness of genomic predictions for daily gain in pigs. In the analysis of daily gain, four linear models were used: 1) a simple additive genetic model (MA), 2) a model including both additive and additive by additive epistatic genetic effects (MAE), 3) a model including both additive and dominance genetic effects (MAD), and 4) a full model including all three genetic components (MAED). Estimates of narrow-sense heritability were 0.397, 0.373, 0.379 and 0.357 for models MA, MAE, MAD and MAED, respectively. Estimated dominance variance and additive by additive epistatic variance accounted for 5.6% and 9.5% of the total phenotypic variance, respectively. Based on model MAED, the estimate of broad-sense heritability was 0.506. Reliabilities of genomic predicted breeding values for the animals without performance records were 28.5%, 28.8%, 29.2% and 29.5% for models MA, MAE, MAD and MAED, respectively. In addition, models including non-additive genetic effects improved unbiasedness of genomic predictions.
People may deny responsibility for negative consequences of their actions by claiming that they were “only obeying orders.” The “Nuremberg defense” offers one extreme example, though it is often ...dismissed as merely an attempt to avoid responsibility. Milgram’s classic laboratory studies reported widespread obedience to an instruction to harm, suggesting that social coercion may alter mechanisms of voluntary agency, and hence abolish the normal experience of being in control of one’s own actions. However, Milgram’s and other studies relied on dissembling and on explicit measures of agency, which are known to be biased by social norms. Here, we combined coercive instructions to administer harm to a co-participant, with implicit measures of sense of agency, based on perceived compression of time intervals between voluntary actions and their outcomes, and with electrophysiological recordings. In two experiments, an experimenter ordered a volunteer to make a key-press action that caused either financial penalty or demonstrably painful electric shock to their co-participant, thereby increasing their own financial gain. Coercion increased the perceived interval between action and outcome, relative to a situation where participants freely chose to inflict the same harms. Interestingly, coercion also reduced the neural processing of the outcomes of one’s own action. Thus, people who obey orders may subjectively experience their actions as closer to passive movements than fully voluntary actions. Our results highlight the complex relation between the brain mechanisms that generate the subjective experience of voluntary actions and social constructs, such as responsibility.
•Responsibility for action is a key feature of human societies•It depends on association between actions and outcomes in the brain•Claims of reduced responsibility are sometimes based on “only obeying orders”•Two experiments suggest coercion can reduce implicit measures of sense of agency
Acting under coercion modifies the subjective experience of being the author of an action, reducing the perceived temporal association between actions and outcomes. Caspar et al. show that the neural processing of action outcomes under coercion more closely resembles situations of passive movement than actions carried out intentionally.
Since development of the Utstein style recommendations for the uniform reporting of cardiac arrest, increasing numbers of national and regional out-of-hospital cardiac arrest (OHCA) registries have ...been established worldwide. The International Liaison Committee on Resuscitation (ILCOR) created the Research and Registries Working Group and aimed to systematically report data collected from these registries.
We conducted two surveys of voluntarily participating national and regional registries. The first survey aimed to identify which core elements of the current Utstein style for OHCA were collected by each registry. The second survey collected descriptive summary data from each registry. We chose the data collected for the second survey based on the availability of core elements identified by the first survey.
Seven national and four regional registries were included in the first survey and nine national and seven regional registries in the second survey. The estimated annual incidence of emergency medical services (EMS)-treated OHCA was 30.0–97.1 individuals per 100,000 population. The combined data showed the median age varied from 64 to 79 years and more than half were male in all 16 registries. The provision of bystander cardiopulmonary resuscitation (CPR) and bystander automated external defibrillator (AED) use was 19.1–79.0% in all registries and 2.0–37.4% among 11 registries, respectively. Survival to hospital discharge or 30-day survival after EMS-treated OHCA was 3.1–20.4% across all registries. Favorable neurological outcome at hospital discharge or 30 days after EMS-treated OHCA was 2.8–18.2%. Survival to hospital discharge or 30-day survival after bystander-witnessed shockable OHCA ranged from 11.7% to 47.4% and favorable neurological outcome from 9.9% to 33.3%.
This report from ILCOR describes data on systems of care and outcomes following OHCA from nine national and seven regional registries across the world. We found variation in reported survival outcomes and other core elements of the current Utstein style recommendations for OHCA across nations and regions.
Genetic evaluation based on information from phenotypes, pedigree and markers can be implemented using a recently developed single-step method. In this paper we compare accuracies of predicted ...breeding values for daily gain and feed conversion ratio (FCR) in Danish Duroc pigs obtained from different versions of single-step methods, the traditional pedigree-based method and the genomic BLUP (GBLUP) method. In particular, we present a single-step method with an adjustment of the genomic relationship matrix so that it is compatible to the pedigree-based relationship matrix. Comparisons are made for both genotyped and non-genotyped animals and univariate and bivariate models. The results show that the three methods with marker information (two single-step methods and GBLUP) produce more accurate predictions of genotyped animals than the pedigree-based method. In addition, single-step methods provide more accurate predictions for non-genotyped animals. The results also show that the single-step method with adjusted genomic relationship matrix produce more accurate predictions than the original single-step method. Finally, the results for the bivariate analyses show a somewhat improved accuracy and reduced inflation of predictions for FCR for the two single-step methods compared with the univariate analyses. The conclusions are: first, the methods with marker information improve prediction compared with the pedigree-based method; second, a single-step method, contrary to GBLUP, provides improved predictions for all animals compared to the pedigree-based method; and third, a single-step method should be used with an adjustment of the genomic relationship matrix.
The onset of the COVID-19 pandemic commenced an era of widespread disruptions in the academic world, including shut downs, periodic shifts to online learning, and disengagement from students. In an ...effort to transition back to in-person learning, many universities and schools tried to implement policy that balanced student learning with community health. While academic administrators have little control over some aspects of COVID-19 spread, they often choose to use temporary shutdowns of in-person teaching based on perceived hotspots of COVID-19. Specifically, if administrators have substantial evidence of within-group transmission for a class or other academic unit (a "hotspot"), the activities of that class or division of the university might be temporarily moved online. In this article, we describe an approach used to make these types of decisions. Using demographic information and weekly COVID-19 testing outcomes for university students, we use an XGBoost model that produces an estimated probability of testing positive for each student. We discuss variables engineered from the demographic information that increased model fit. As part of our approach, we simulate semesters under the null hypothesis of no in-class transmission, and compare the distribution of simulated outcomes to the observed group positivity rates to find an initial p-value for each group (e.g., section, housing area, or major). Using a simulation-based modification of a standard false discovery rate procedure, we identify possible hot spots-classes or groups whose COVID-19 rates exceed the levels expected for the demographic mix of students in each group of interest. We use simulation experiments and an anonymized example from Fall 2020 to illustrate the performance of our approach. While our example is based on hotspot detection in a university setting, the approach can be used for monitoring the spread of infectious disease within any interconnected organization or population.
Non-indigenous species (NIS) can impact marine biodiversity and ecosystem structure and function. Once introduced into a new region, secondary dispersal is limited by the physiology of the organism ...in relation to the ambient environment and by complex interactions between a suite of ecological factors such as presence of predators, competitors, and parasites. Early prediction of dispersal potential and future 'area of impact' is challenging, but also a great asset in taking appropriate management actions. Aerobic scope (AS) in fish has been linked to various fitness-related parameters, and may be valuable in determining dispersal potential of aquatic invasive species in novel environments. Round goby, Neogobius melanostomus, one of the most wide-ranging invasive fish species in Europe and North America, currently thrives in brackish and fresh water, but its ability to survive in high salinity waters is unknown to date. We show that AS in round goby is reduced by 30% and blood plasma osmolality increased (indicating reduced capacity for osmoregulation) at salinities approaching oceanic conditions, following slow ramping (5 PSU per week) and subsequent long-term acclimation to salinities ranging between 0 and 30 PSU (8 days at final treatment salinities before blood plasma osmolality measurements, 12-20 additional days before respirometry). Survival was also reduced at the highest salinities yet a significant proportion (61%) of the fish survived at 30 PSU. Reduced physiological performance at the highest salinities may affect growth and competitive ability under oceanic conditions, but to what extent reduced AS and osmoregulatory capacity will slow the current 30 km year-1 rate of advance of the species through the steep salinity gradient from the brackish Baltic Sea and into the oceanic North Sea remains speculative. An unintended natural experiment is in progress to test whether the rate of advance slows down. At the current rate of advance the species will reach the oceanic North Sea by 2018/2019, therefore time for taking preventative action is short.
We present 3–50 keV NuSTAR observations of the active galactic nuclei Mrk 335 in a very low flux state. The spectrum is dominated by very strong features at the energies of the iron line at 5–7 keV ...and Compton hump from 10–30 keV. The source is variable during the observation, with the variability concentrated at low energies, which suggesting either a relativistic reflection or a variable absorption scenario. In this work, we focus on the reflection interpretation, making use of new relativistic reflection models that self consistently calculate the reflection fraction, relativistic blurring and angle-dependent reflection spectrum for different coronal heights to model the spectra. We find that the spectra can be well fitted with relativistic reflection, and that the lowest flux state spectrum is described by reflection alone, suggesting the effects of extreme light-bending occurring within ∼2 gravitational radii (R
G) of the event horizon. The reflection fraction decreases sharply with increasing flux, consistent with a point source moving up to above 10 R
G as the source brightens. We constrain the spin parameter to greater than 0.9 at the 3σ confidence level. By adding a spin-dependent upper limit on the reflection fraction to our models, we demonstrate that this can be a powerful way of constraining the spin parameter, particularly in reflection dominated states. We also calculate a detailed emissivity profile for the iron line, and find that it closely matches theoretical predictions for a compact source within a few R
G of the black hole.
The majority of ultraluminous X-ray sources are point sources that are spatially offset from the nuclei of nearby galaxies and whose X-ray luminosities exceed the theoretical maximum for spherical ...infall (the Eddington limit) onto stellar-mass black holes. Their X-ray luminosities in the 0.5-10 kiloelectronvolt energy band range from 10(39) to 10(41) ergs per second. Because higher masses imply less extreme ratios of the luminosity to the isotropic Eddington limit, theoretical models have focused on black hole rather than neutron star systems. The most challenging sources to explain are those at the luminous end of the range (more than 10(40) ergs per second), which require black hole masses of 50-100 times the solar value or significant departures from the standard thin disk accretion that powers bright Galactic X-ray binaries, or both. Here we report broadband X-ray observations of the nuclear region of the galaxy M82 that reveal pulsations with an average period of 1.37 seconds and a 2.5-day sinusoidal modulation. The pulsations result from the rotation of a magnetized neutron star, and the modulation arises from its binary orbit. The pulsed flux alone corresponds to an X-ray luminosity in the 3-30 kiloelectronvolt range of 4.9 × 10(39) ergs per second. The pulsating source is spatially coincident with a variable source that can reach an X-ray luminosity in the 0.3-10 kiloelectronvolt range of 1.8 × 10(40) ergs per second. This association implies a luminosity of about 100 times the Eddington limit for a 1.4-solar-mass object, or more than ten times brighter than any known accreting pulsar. This implies that neutron stars may not be rare in the ultraluminous X-ray population, and it challenges physical models for the accretion of matter onto magnetized compact objects.
Humans primarily interact with information technology through glass touch screens, and the world would indeed be unrecognizable without glass. However, the low toughness of oxide glasses continues to ...be their Achilles heel, limiting both future applications and the possibility to make thinner, more environmentally friendly glasses. Here, we show that with proper control of plasticity mechanisms, record-high values of fracture toughness for transparent bulk oxide glasses can be achieved. Through proper combination of gas-mediated permanent densification and rational composition design, we increase the glasses’ propensity for plastic deformation. Specifically, we demonstrate a fracture toughness of an aluminoborate glass (1.4 MPa m0.5) that is twice as high as that of commercial glasses for mobile devices. Atomistic simulations reveal that the densification of the adaptive aluminoborate network increases coordination number changes and bond swapping, ultimately enhancing plasticity and toughness upon fracture. Our findings thus provide general insights into the intrinsic toughening mechanisms of oxide glasses.
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