Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers

Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968.Objective: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking.Data Sources: Primary data.Study Selection: Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy.DataExtraction: Uniform statistical analysis scripts were runlocally. Starting with 94 050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD 16 years), and a logistic regression of heavy vs light smoking with ther s16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum.Data Synthesis: Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR]=1.45; 95% CI, 1.36-1.55; n=13 843) than were carriers of the risk allele who were late-onset smokers (OR=1.27; 95% CI, 1.21-1.33, n=19 505) (P=.01).Conclusion: These results highlight an increased genetic vulnerability to smoking in early-onset smokers

Simulated Microgravity Alters Gene Regulation Linked to Immunity and Cardiovascular Disease

Microgravity exposure induces a cephalad fluid shift and an overall reduction in physical activity levels which can lead to cardiovascular deconditioning in the absence of countermeasures. Future spaceflight missions will expose crew to extended periods of microgravity among other stressors, the effects of which on cardiovascular health are not fully known. In this study, we determined cardiac responses to extended microgravity exposure using the rat hindlimb unloading (HU) model. We hypothesized that exposure to prolonged simulated microgravity and subsequent recovery would lead to increased oxidative damage and altered expression of genes involved in the oxidative response. To test this hypothesis, we examined hearts of male (three and nine months of age) and female (3 months of age) Long-Evans rats that underwent HU for various durations up to 90 days and reambulated up to 90 days post-HU. Results indicate sex-dependent changes in oxidative damage marker 8-hydroxydeoxyguanosine (8-OHdG) and antioxidant gene expression in left ventricular tissue. Three-month-old females displayed elevated 8-OHdG levels after 14 days of HU while age-matched males did not. In nine-month-old males, there were no differences in 8-OHdG levels between HU and normally loaded control males at any of the timepoints tested following HU. RNAseq analysis of left ventricular tissue from nine-month-old males after 14 days of HU revealed upregulation of pathways involved in pro-inflammatory signaling, immune cell activation and differential expression of genes associated with cardiovascular disease progression. Taken together, these findings provide a rationale for targeting antioxidant and immune pathways and that sex differences should be taken into account in the development of countermeasures to maintain cardiovascular health in space

Quasi-three-level Model Applied to Measured Spectra of Nonlinear Absorption and Refraction in Organic Molecules

Materials with a large nonlinear refractive index (2) and relatively small linear and nonlinear absorption losses, namely, two-photon absorption (2PA, of coefficient 2), have long been sought after for applications such as all-optical switching (AOS). Here we experimentally determine the linear and 2PA properties of several organic molecules, which we approximate as centrosymmetric, and use a simplified essential-state model (quasi-three-level model) to predict the dispersion of 2. We then compare these predictions with experimental measurements of 2 and find good agreement. Here “quasi”-three-level means using a single one-photon allowed intermediate state and multiple (here two) two-photon allowed states. This also allows predictions of the figure-of-merit (FOM), defined as the ratio of nonlinear refractive phase shift to the 2PA fractional loss, that determines the viability for such molecules to be used in device applications. The model predicts that the optimized wavelength range for a large FOM lies near the short wavelength linear absorption edge for cyanine-like dyes where the magnitude of 2 is quite large. However, 2PA bands lying close to the linear absorption edge in certain classes of molecules can greatly reduce this FOM. We identify two molecules having a large FOM for AOS. We note that the FOM is often defined as the ratio of real to imaginary parts of the third-order susceptibility ((3)) with multiple processes leading to both components. As explained later in this paper, such definitions require care to only include the 2PA contribution to the imaginary part of (3) in regions of transparency.Abstract © 2016 Optical Society of Americ

Linearly polarized, 3.35 W narrow-linewidth, 1150 nm fiber master oscillator power amplifier for frequency doubling to the yellow

A high-power linearly polarized Yb-doped silica fiber master oscillator power amplifier at 1150 nm is reported. It produced 3.35 W cw and 2.33 W of average power in 1 s pulses at a 100 kHz repetition rate, both with 8 pm linewidth. This is the first report, to the best of our knowledge, of a high-power Yb-doped fiber amplifier at a wavelength longer than 1135 nm. The pulsed output was frequency doubled in a bulk periodically poled near-stoichiometric LiTaO 3 chip to generate 976 mW of average power at 575 nm with an overall system optical-to-optical efficiency of 9.8% with respect to launched pump power

Functional and transcriptional characterization of complex neuronal co-cultures

Brain-on-a-chip systems are designed to simulate brain activity using traditional in vitro cell culture on an engineered platform. It is a noninvasive tool to screen new drugs, evaluate toxicants, and elucidate disease mechanisms. However, successful recapitulation of brain function on these systems is dependent on the complexity of the cell culture. In this study, we increased cellular complexity of traditional (simple) neuronal cultures by co-culturing with astrocytes and oligodendrocyte precursor cells (complex culture). We evaluated and compared neuronal activity (e.g., network formation and maturation), cellular composition in long-term culture, and the transcriptome of the two cultures. Compared to simple cultures, neurons from complex co-cultures exhibited earlier synapse and network development and maturation, which was supported by localized synaptophysin expression, up-regulation of genes involved in mature neuronal processes, and synchronized neural network activity. Also, mature oligodendrocytes and reactive astrocytes were only detected in complex cultures upon transcriptomic analysis of age-matched cultures. Functionally, the GABA antagonist bicuculline had a greater influence on bursting activity in complex versus simple cultures. Collectively, the cellular complexity of brain-on-a-chip systems intrinsically develops cell type-specific phenotypes relevant to the brain while accelerating the maturation of neuronal networks, important features underdeveloped in traditional cultures

Referral Criteria for Specialist Palliative Care for Patients With Dementia

Importance: Patients with dementia have considerable supportive care needs. Specialist palliative care may be beneficial, but it is unclear which patients are most appropriate for referral and when they should be referred.Objective: To identify a set of consensus referral criteria for specialist palliative care for patients with dementia. Design, Setting, and Participants: In this survey study using 3 rounds of Delphi surveys, an international, multidisciplinary panel of clinicians from 5 continents with expertise in the integration of dementia and palliative care were asked to rate 83 putative referral criteria (generated from a previous systematic review and steering committee discussion). Specialist palliative care was defined as an interdisciplinary team consisting of practitioners with advanced knowledge and skills in palliative medicine offering consultative services for specialist-level palliative care in (nonhospice) inpatient, outpatient, community, and home-based settings. Main Outcomes and Measures: Consensus was defined a priori as at least 70% agreement among experts. A criterion was coded as major if the experts advocated that meeting 1 criterion alone was satisfactory to justify a referral. Data were summarized using descriptive statistics. Results: Of the 63 invited and eligible panelists, the response rate was 58 (92.1%) in round 1, 58 (92.1%) in round 2, and 60 (95.2%) in round 3. Of the 58 panelists who provided demographic data in round 1, most were aged 40 to 49 years (28 of 58 [48.3%]), and 29 panelists (50%) each were men and women. Panelists achieved consensus on 15 major and 42 minor criteria for specialist palliative care referral. The 15 major criteria were grouped under 5 categories, including dementia type (eg, rapidly progressive dementia), symptom distress (eg, severe physical symptoms), psychosocial factors or decision-making (eg, request for hastened death, assisted suicide, or euthanasia), comorbidities or complications (eg, ≥2 episodes of aspiration pneumonia in the past 12 months); and hospital use (eg, ≥2 hospitalizations within the past 3 months). Conclusions and Relevance: In this Delphi survey study, international experts reached consensus on a range of criteria for referral to specialist palliative care. With testing and validation, these criteria may be used to standardize specialist palliative care access for patients with dementia across various care settings.</p

Synergies between biodiversity conservation and ecosystem service provision: lessons on integrated ecosystem service valuation from a Himalayan protected area, Nepal.

We utilised a practical approach to integrated ecosystem service valuation to inform decision-making at Shivapuri-Nagarjun National Park in Nepal. The Toolkit for Ecosystem Service Site-based Assessment (TESSA) was used to compare ecosystem services between two alternative states of the site (protection or lack of protection with consequent changed land use) to estimate the net consequences of protection. We estimated that lack of protection would have substantially reduced the annual ecosystem service flow, including a 74% reduction in the value of greenhouse gas sequestration, 60% reduction in carbon storage, 94% reduction in nature-based recreation, and 88% reduction in water quality. The net monetary benefit of the park was estimated at $11 million year-1. We conclude that: (1) simplified cost-benefit analysis between alternative states can be usefully employed to determine the ecosystem service consequences of land-use change, but monetary benefits should be subject to additional sensitivity analysis; (2) both biophysical indicators and monetary values can be standardised using rose plots, to illustrate the magnitude of synergies and trade-offs among the services; and (3) continued biodiversity protection measures can preserve carbon stock, although the benefit of doing so remains virtual unless an effective governance option is established to realise the monetary values

Role of carbon cycle observations and knowledge in carbon management

Author Posting. © Annual Reviews, 2003. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Environment and Resources 28 (2003): 521-558, doi:10.1146/annurev.energy.28.011503.163443.Agriculture and industrial development have led to inadvertent changes in the natural carbon cycle. As a consequence, concentrations of carbon dioxide and other greenhouse gases have increased in the atmosphere and may lead to changes in climate. The current challenge facing society is to develop options for future management of the carbon cycle. A variety of approaches has been suggested: direct reduction of emissions, deliberate manipulation of the natural carbon cycle to enhance sequestration, and capture and isolation of carbon from fossil fuel use. Policy development to date has laid out some of the general principles to which carbon management should adhere. These are summarized as: how much carbon is stored, by what means, and for how long. To successfully manage carbon for climate purposes requires increased understanding of carbon cycle dynamics and improvement in the scientific capabilities available for measurement as well as for policy needs. The specific needs for scientific information to underpin carbon cycle management decisions are not yet broadly known. A stronger dialogue between decision makers and scientists must be developed to foster improved application of scientific knowledge to decisions. This review focuses on the current knowledge of the carbon cycle, carbon measurement capabilities (with an emphasis on the continental scale) and the relevance of carbon cycle science to carbon sequestration goals.The National Center for Atmospheric Research is supported by the National Science Foundation