Genetic partitioning of interleukin-6 signalling in mice dissociates Stat3 from Smad3-mediated lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal disease that is unresponsive to current therapies and characterized by excessive collagen deposition and subsequent fibrosis. While inflammatory cytokines, including interleukin (IL)-6, are elevated in IPF, the molecular mechanisms that underlie this disease are incompletely understood, although the development of fibrosis is believed to depend on canonical transforming growth factor (TGF)-β signalling. We examined bleomycin-induced inflammation and fibrosis in mice carrying a mutation in the shared IL-6 family receptor gp130. Using genetic complementation, we directly correlate the extent of IL-6-mediated, excessive Stat3 activity with inflammatory infiltrates in the lung and the severity of fibrosis in corresponding gp130757F mice. The extent of fibrosis was attenuated in B lymphocyte-deficient gp130757F;µMT−/− compound mutant mice, but fibrosis still occurred in their Smad3−/− counterparts consistent with the capacity of excessive Stat3 activity to induce collagen 1α1 gene transcription independently of canonical TGF-β/Smad3 signalling. These findings are of therapeutic relevance, since we confirmed abundant STAT3 activation in fibrotic lungs from IPF patients and showed that genetic reduction of Stat3 protected mice from bleomycin-induced lung fibrosis

Quantum central limit theorem for continuous-time quantum walks on odd graphs in quantum probability theory

The method of the quantum probability theory only requires simple structural data of graph and allows us to avoid a heavy combinational argument often necessary to obtain full description of spectrum of the adjacency matrix. In the present paper, by using the idea of calculation of the probability amplitudes for continuous-time quantum walk in terms of the quantum probability theory, we investigate quantum central limit theorem for continuous-time quantum walks on odd graphs.Comment: 19 page, 1 figure

Race, ethnicity and risk of second primary contralateral breast cancer in the United States

Breast cancer survivors have a high risk of a second primary contralateral breast cancer (CBC), but there are few studies of CBC risk in racial/ethnic minority populations. We examined whether the incidence and risk factors for CBC differed by race/ethnicity in the United States. Women with a first invasive Stage I-IIB breast cancer diagnosis at ages 20-74 years between 2000 and 2015 in the Surveillance, Epidemiology, and End Results Program (SEER) 18 registries were followed through 2016 for a diagnosis of invasive CBC ≥1 year after the first breast cancer diagnosis. We used cause-specific Cox proportional hazards models to test the association between race/ethnicity and CBC, adjusting for age, hormone receptor status, radiation therapy, chemotherapy and stage at first diagnosis, and evaluated the impact of contralateral prophylactic mastectomy, socioeconomic status, and insurance status on the association. After a median follow-up of 5.9 years, 9247 women (2.0%) were diagnosed with CBC. Relative to non-Hispanic (NH) White women, CBC risk was increased in NH Black women (hazard ratio = 1.44, 95% CI 1.35-1.54) and Hispanic women (1.11, 95% CI 1.02-1.20), with the largest differences among women diagnosed at younger ages. Adjustment for contralateral prophylactic mastectomy, socioeconomic status and health insurance did not explain the associations. Therefore, non-Hispanic Black and Hispanic women have an increased risk of CBC that is not explained by clinical or socioeconomic factors collected in SEER. Large studies of diverse breast cancer survivors with detailed data on treatment delivery and adherence are needed to inform interventions to reduce this disparity

Ownership of co-creation assets: driving B2B value propositions in the service economy

The benefits of specialization have been driving the rise of the service economy and pushing capability frontiers and economic growth. In service economies, almost any activity, asset, and skill can be bought on competitive markets, making it harder to build competitive advantage on any of those inputs. Against that background, the question emerges what constitutes sustainable value propositions of service providers. Drawing on an emerging stream of research on the non-ownership value of services, we argue that service providers create value by taking on ownership of service assets and thereby transform uncertainty of value creation into economic opportunities. In our view, service providers offer the essential value proposition of transforming their clients’ uncertainty downsides into opportunities related to assets such as vehicles, real estate, equipment and computing platforms. Clients benefit by delegating ownership of assets to the domain of a service provider. In turn, clients can focus their investment on their most promising assets. Service providers create sustainable competitive advantage by assuming ownership and excelling at the management of (a) unique physical assets, (b) unique intangible assets and (c) maintaining an appropriate architecture of social capital through customer relationships and business ecosystems

Psychometric Evidence of a Multidimensional Measure of Prosocial Behaviors for Spanish Adolescents

Prior theories and scholars rarely distinguished between distinct forms of prosocial behaviors (i.e., actions intended to benefit others) and most scholars operationalize prosocial behaviors as a global construct. Furthermore, stringent tests of psychometric properties of prosocial behavior measures are rare, especially in countries other than the United States. The present study was designed to examine the structure and functions of a multidimensional measure of prosocial behaviors in youth from Spain. Six hundred and 66 adolescents (46% girls; M age = 15.33 years, SD = 0.47 years) from Valencia, Spain, completed the Prosocial Tendencies Measure-Revised (PTM-R), measures of sympathy, perspective taking, and a global measure of prosocial behavior. Results showed that the hypothesized 6-factor structure of the PTM-R had good fit, the best fit model as compared to alternative models, and that there were several unique patterns of relations between specific forms of prosocial behaviors and sympathy, perspective taking, and the global measure of prosocial behavior. Furthermore, although there were significant gender differences in some forms of prosocial behaviors, the structure of the PTM-R was equivalent across gender. Discussion focuses on the implications for theories and measurement of prosocial behaviors

Multiwavelength L-band fiber laser with bismuth-oxide EDF and photonic crystal fiber.

A multiwavelength laser comb using a bismuth-based erbium-doped fiber and 50 m photonic crystal fiber is demonstrated in a ring cavity configuration. The fiber laser is solely pumped by a single 1455 nm Raman pump laser to exploit its higher power delivery compared to that of a single-mode laser diode pump. At 264 mW Raman pump power and 1 mW Brillouin pump power, 38 output channels in the L-band have been realized with an optical signal-to-noise ratio above 15 dB and a Stokes line spacing of 0.08 nm. The laser exhibits a tuning range of 12 nm and produces stable Stokes lines across the tuning range between Brillouin pump wavelengths of 1603 nm and 1615 nm

Effects of sleep deprivation on neural functioning: an integrative review

Sleep deprivation has a broad variety of effects on human performance and neural functioning that manifest themselves at different levels of description. On a macroscopic level, sleep deprivation mainly affects executive functions, especially in novel tasks. Macroscopic and mesoscopic effects of sleep deprivation on brain activity include reduced cortical responsiveness to incoming stimuli, reflecting reduced attention. On a microscopic level, sleep deprivation is associated with increased levels of adenosine, a neuromodulator that has a general inhibitory effect on neural activity. The inhibition of cholinergic nuclei appears particularly relevant, as the associated decrease in cortical acetylcholine seems to cause effects of sleep deprivation on macroscopic brain activity. In general, however, the relationships between the neural effects of sleep deprivation across observation scales are poorly understood and uncovering these relationships should be a primary target in future research

Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review.

The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer. Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts. The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes

The Clinical Sequencing Evidence-Generating Research Consortium: Integrating Genomic Sequencing in Diverse and Medically Underserved Populations

The Clinical Sequencing Evidence-Generating Research (CSER) consortium, now in its second funding cycle, is investigating the effectiveness of integrating genomic (exome or genome) sequencing into the clinical care of diverse and medically underserved individuals in a variety of healthcare settings and disease states. The consortium comprises a coordinating center, six funded extramural clinical projects, and an ongoing National Human Genome Research Institute (NHGRI) intramural project. Collectively, these projects aim to enroll and sequence over 6,100 participants in four years. At least 60% of participants will be of non-European ancestry or from underserved settings, with the goal of diversifying the populations that are providing an evidence base for genomic medicine. Five of the six clinical projects are enrolling pediatric patients with various phenotypes. One of these five projects is also enrolling couples whose fetus has a structural anomaly, and the sixth project is enrolling adults at risk for hereditary cancer. The ongoing NHGRI intramural project has enrolled primarily healthy adults. Goals of the consortium include assessing the clinical utility of genomic sequencing, exploring medical follow up and cascade testing of relatives, and evaluating patient-provider-laboratory level interactions that influence the use of this technology. The findings from the CSER consortium will offer patients, healthcare systems, and policymakers a clearer understanding of the opportunities and challenges of providing genomic medicine in diverse populations and settings, and contribute evidence toward developing best practices for the delivery of clinically useful and cost-effective genomic sequencing in diverse healthcare settings