No Tradeoff between Coherence and Sub-Poissonianity for Heisenberg-Limited Lasers.

The Heisenberg limit to laser coherence C-the number of photons in the maximally populated mode of the laser beam-is the fourth power of the number of excitations inside the laser. We generalize the previous proof of this upper bound scaling by dropping the requirement that the beam photon statistics be Poissonian (i.e., Mandel's Q=0). We then show that the relation between C and sub-Poissonianity (Q<0) is win-win, not a tradeoff. For both regular (non-Markovian) pumping with semiunitary gain (which allows Q→-1), and random (Markovian) pumping with optimized gain, C is maximized when Q is minimized.

Pragmatic sedation strategies to prevent secondary brain injury in low-resource settings.

Traumatic brain injury is the alteration in brain function due to an external force. It is common and affects millions of people worldwide annually. The World Health Organization estimates that 90% of global deaths caused by injuries occur in low- and middle-income countries, with traumatic brain injury contributing up to half of these trauma-related deaths. Patients with traumatic brain injury in low- and middle-income countries have twice the odds of dying compared with their counterparts in high-income countries. Sedation is a key element of care in the management of traumatic brain injury, used for its neuroprotective effects and to prevent secondary brain injury. While sedatives have the potential to improve outcomes, they can be challenging to administer and have potentially dangerous complications. Sedation in low-resource settings should aim to be effective, safe, affordable and feasible. In this paper, we summarise the indications for sedation in traumatic brain injury, the choice of sedative drugs and the pragmatic management and monitoring of sedated traumatic brain injury patients in low-resource settings.

Long-term decline of the Amazon carbon sink.

Atmospheric carbon dioxide records indicate that the land surface has acted as a strong global carbon sink over recent decades, with a substantial fraction of this sink probably located in the tropics, particularly in the Amazon. Nevertheless, it is unclear how the terrestrial carbon sink will evolve as climate and atmospheric composition continue to change. Here we analyse the historical evolution of the biomass dynamics of the Amazon rainforest over three decades using a distributed network of 321 plots. While this analysis confirms that Amazon forests have acted as a long-term net biomass sink, we find a long-term decreasing trend of carbon accumulation. Rates of net increase in above-ground biomass declined by one-third during the past decade compared to the 1990s. This is a consequence of growth rate increases levelling off recently, while biomass mortality persistently increased throughout, leading to a shortening of carbon residence times. Potential drivers for the mortality increase include greater climate variability, and feedbacks of faster growth on mortality, resulting in shortened tree longevity. The observed decline of the Amazon sink diverges markedly from the recent increase in terrestrial carbon uptake at the global scale, and is contrary to expectations based on models.

Opportunities for intervention and innovation in school food within UK schools.

We have recently been funded by the UK Prevention Research Partnership (UKPRP) to develop a UK school food network. The overarching aim is to build a community working towards a more health-promoting food and nutrition system in UK schools (primary and secondary). Here we describe the current status of school food research, including a review of the literature supporting the health-promoting schools approach and outline the opportunities for intervention and innovation establishment of the network present. Key potential school food research themes are described, and their prioritisation within the network, as well as network activities that have been planned, with the ultimate ambition of reducing socio-economic diet-related inequalities, and, consequently, non-communicable disease risk.

Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence.

Cigarette smoking is a leading cause of preventable mortality worldwide. Nicotine dependence, which reduces the likelihood of quitting smoking, is a heritable trait with firmly established associations with sequence variants in nicotine acetylcholine receptor genes and at other loci. To search for additional loci, we conducted a genome-wide association study (GWAS) meta-analysis of nicotine dependence, totaling 38,602 smokers (28,677 Europeans/European Americans and 9925 African Americans) across 15 studies. In this largest-ever GWAS meta-analysis for nicotine dependence and the largest-ever cross-ancestry GWAS meta-analysis for any smoking phenotype, we reconfirmed the well-known CHRNA5-CHRNA3-CHRNB4 genes and further yielded a novel association in the DNA methyltransferase gene DNMT3B. The intronic DNMT3B rs910083-C allele (frequency=44-77%) was associated with increased risk of nicotine dependence at P=3.7 × 10-8 (odds ratio (OR)=1.06 and 95% confidence interval (CI)=1.04-1.07 for severe vs mild dependence). The association was independently confirmed in the UK Biobank (N=48,931) using heavy vs never smoking as a proxy phenotype (P=3.6 × 10-4, OR=1.05, and 95% CI=1.02-1.08). Rs910083-C is also associated with increased risk of squamous cell lung carcinoma in the International Lung Cancer Consortium (N=60,586, meta-analysis P=0.0095, OR=1.05, and 95% CI=1.01-1.09). Moreover, rs910083-C was implicated as a cis-methylation quantitative trait locus (QTL) variant associated with higher DNMT3B methylation in fetal brain (N=166, P=2.3 × 10-26) and a cis-expression QTL variant associated with higher DNMT3B expression in adult cerebellum from the Genotype-Tissue Expression project (N=103, P=3.0 × 10-6) and the independent Brain eQTL Almanac (N=134, P=0.028). This novel DNMT3B cis-acting QTL variant highlights the importance of genetically influenced regulation in brain on the risks of nicotine dependence, heavy smoking and consequent lung cancer.

Nicotine dependence is associated with functional variation in FMO3, an enzyme that metabolizes nicotine in the brain.

A common haplotype of the flavin-containing monooxygenase gene FMO3 is associated with aberrant mRNA splicing, a twofold reduction in in vivo nicotine N-oxidation and reduced nicotine dependence. Tobacco remains the largest cause of preventable mortality worldwide. CYP2A6, the primary hepatic nicotine metabolism gene, is robustly associated with cigarette consumption but other enzymes contribute to nicotine metabolism. We determined the effects of common variants in FMO3 on plasma levels of nicotine-N-oxide in 170 European Americans administered deuterated nicotine. The polymorphism rs2266780 (E308G) was associated with N-oxidation of both orally administered and ad libitum smoked nicotine (P⩽3.3 × 10-5 controlling for CYP2A6 genotype). In vitro, the FMO3 G308 variant was not associated with reduced activity, but rs2266780 was strongly associated with aberrant FMO3 mRNA splicing in both liver and brain (P⩽6.5 × 10-9). Surprisingly, in treatment-seeking European American smokers (n=1558) this allele was associated with reduced nicotine dependence, specifically with a longer time to first cigarette (P=9.0 × 10-4), but not with reduced cigarette consumption. As N-oxidation accounts for only a small percentage of hepatic nicotine metabolism we hypothesized that FMO3 genotype affects nicotine metabolism in the brain (unlike CYP2A6, FMO3 is expressed in human brain) or that nicotine-N-oxide itself has pharmacological activity. We demonstrate for the first time nicotine N-oxidation in human brain, mediated by FMO3 and FMO1, and show that nicotine-N-oxide modulates human α4ß2 nicotinic receptor activity in vitro. These results indicate possible mechanisms for associations between FMO3 genotype and smoking behaviors, and suggest nicotine N-oxidation as a novel target to enhance smoking cessation.

Strong Constraints on Cosmological Gravity from GW170817 and GRB 170817A.

The detection of an electromagnetic counterpart (GRB 170817A) to the gravitational-wave signal (GW170817) from the merger of two neutron stars opens a completely new arena for testing theories of gravity. We show that this measurement allows us to place stringent constraints on general scalar-tensor and vector-tensor theories, while allowing us to place an independent bound on the graviton mass in bimetric theories of gravity. These constraints severely reduce the viable range of cosmological models that have been proposed as alternatives to general relativistic cosmology.

Threats to intact tropical peatlands and opportunities for their conservation.

Large, intact areas of tropical peatland are highly threatened at a global scale by the expansion of commercial agriculture and other forms of economic development. Conserving peatlands on a landscape scale, with their hydrology intact, is of international conservation importance to preserve their distinctive biodiversity and ecosystem services and maintain their resilience to future environmental change. We explored threats to and opportunities for conserving remaining intact tropical peatlands; thus, we excluded peatlands of Indonesia and Malaysia, where extensive deforestation, drainage, and conversion to plantations means conservation in this region can protect only small fragments of the original ecosystem. We focused on a case study, the Pastaza-Marañón Foreland Basin (PMFB) in Peru, which is among the largest known intact tropical peatland landscapes in the world and is representative of peatland vulnerability. Maintenance of the hydrological conditions critical for carbon storage and ecosystem function of peatlands is, in the PMFB, primarily threatened by expansion of commercial agriculture linked to new transport infrastructure that is facilitating access to remote areas. There remain opportunities in the PMFB and elsewhere to develop alternative, more sustainable land-use practices. Although some of the peatlands in the PMFB fall within existing legally protected areas, this protection does not include the most carbon-dense (domed pole forest) areas. New carbon-based conservation instruments (e.g., REDD+, Green Climate Fund), developing markets for sustainable peatland products, transferring land title to local communities, and expanding protected areas offer pathways to increased protection for intact tropical peatlands in Amazonia and elsewhere, such as those in New Guinea and Central Africa which remain, for the moment, broadly beyond the frontier of commercial development.

Complications and Their Resolution in Recipients of Deceased and Living Donor Liver Transplants: Findings From the A2ALL Cohort Study.

The purpose of this study was to explore long-term complications in recipients of deceased donor liver transplant (DDLT) and living donor liver transplant (LDLT) in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). We analyzed 471 DDLTs and 565 LDLTs from 1998 to 2010 that were followed up to 10 years for 36 categories of complications. Probabilities of complications and their resolutions were estimated using the Kaplan-Meier method, and predictors were tested in Cox proportional hazards models. Median follow-up for DDLT and LDLT was 4.19 and 4.80 years, respectively. DDLT recipients were more likely to have hepatocellular carcinoma and higher disease severity, including Model for End-Stage Liver Disease score. Complications occurring with higher probability in LDLT included biliary-related complications and hepatic artery thrombosis. In DDLT, ascites, intra-abdominal bleeding, cardiac complications and pulmonary edema were significantly more probable. Development of chronic kidney disease stage 4 or 5 was less likely in LDLT recipients (hazard ratio [HR] 0.41, p = 0.02). DDLT and LDLT had similar risk of grade 4 complications (HR 0.89, p = 0.60), adjusted for other risk factors. Once a complication occurred, the time to resolution did not differ between LDLT and DDLT. Future efforts should be directed toward reducing the occurrence of complications after liver transplantation.

Optimizing the Point-Source Emission Rates and Geometries of Pheromone Mating Disruption Mega-Dispensers.

High-emission-rate "mega-dispensers" have come into increasing use for sex pheromone mating disruption of moth pests over the past two decades. These commercially available dispensers successfully suppress mating and reduce crop damage when they are deployed at very low to moderate densities, ranging from 1 to 5/ha to 100-1000/ha, depending on the dispenser types and their corresponding pheromone emission rates. Whereas traditionally the emission rates for successful commercial mating disruption formulations have been measured in terms of amounts (usually milligram) emitted by the disruptant application per acre or hectare per day, we suggest that emission rates should be measured on a per-dispenser per-minute basis. In addition we suggest, because of our knowledge concerning upwind flight of male moths being dependent on contact with pheromone plume strands, that more attention needs to be paid to optimizing the flux within plume strands that shear off of any mating disruption dispenser's surface. By measuring the emission rates on a per-minute basis and measuring the plume strand concentrations emanating from the dispensers, it may help improve the ability of the dispensers to initiate upwind flight from males and initiate their habituation to the pheromone farther downwind than can otherwise be achieved. In addition, by optimizing plume strand flux by paying attention to the geometries and compactness of mating disruption mega-dispensers may help reduce the cost of mega-dispenser disruption formulations by improving their behavioral efficacy while maintaining field longevity and using lower loading rates per dispenser.

A telephone reminder intervention to improve breast screening information and access.

OBJECTIVES: In the UK, women aged 50-70 are offered breast cancer screening every three years. Screening participation rates in London have been particularly low. Low rates have been associated with low socio-economic status, and some ethnic groups have been observed to be underserved by cancer screening. This paper reports on a telephone reminder intervention in London Newham, an area of high deprivation and ethnic diversity. STUDY DESIGN: Observational study of planned intervention. METHODS: Women invited for breast screening were telephoned to confirm receipt of the invitation letter, remind invitees of their upcoming appointment, and to provide further information. Aggregate data at general practice level on invitation to and attendance at breast screening and on numbers reached by telephone were analysed by logistic regression. RESULTS: For the 29 participating GP practices (10,928 invitees) overall uptake in 2010 was higher compared to the previous screening round in 2007 (67% vs. 51%; p < 0.001). On average 59% of invitees were reached by the reminder calls. A 10% increase in women reached resulted in an 8% increase in the odds of women attending their screening appointment (95% CI: 5%-11%), after adjusting for 2007 attendance rates. Practices with a higher proportion of South Asian women were associated with a larger uptake adjusted for 2007 uptake and population reached by the telephone intervention, (4% increase in odds of attendance per 10% increase in South Asian population, CI 1%-7%, p = 0.003) while practices with a higher proportion of black women were associated with a smaller uptake similarly adjusted. (11% decrease in odds of attendance per 10% increase in black population, CI 9%-16%, p < 0.001). CONCLUSIONS: A language- and culture-sensitive programme of reminder calls substantially improved breast cancer screening uptake.

Biomarkers for the diagnosis and treatment of rheumatoid arthritis - a systematic review.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease, symmetrically affecting the small joints. Biomarkers are tools that can be used in the diagnosis and monitoring of RA. AIM: To systematically explore the role of the biomarkers: C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated protein (Anti-CCP), 14-3-3η protein, and the multi-biomarker disease activity (MBDA) score for the diagnosis and treatment of RA. METHODS: A systematic review of the English literature using four different databases was carried out. RESULTS: CRP >7.1 mg/L predicted poor conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) outcome in RA. Anti-CCP, CRP ≥0.3 mg/dL, and RF predicted bone erosion and cartilage destruction. Combination of high 14-3-3η protein with RF and CRP improved the prediction of rapid erosion progression (REP). Anti-CCP was not associated with disease activity but was associated with increased radiographic damage (r = 0.46, p = 0.048). RF was not associated with joint damage but correlated with ultrasound-detected bone erosion. The 14-3-3η protein significantly correlated with inflammation, bone rremodeling, and osteoporosis in RA patients (p < 0.05). In addition, the 14-3-3η protein positively correlated with RA duration (p = 0.003), disease aactivity, and positive RF (p = 0.025) and it distinguished early from established RA. Early MBDA scores correlated with later response in disease activity after 6 and 12 weeks of treatment (p < 0.05). The MBDA score was able to differentiate between small differences in disease activity, predicted remission over 1-year pperiod, and was a strong predictor of radiographic progression of RA. CONCLUSION: The investigated biomarkers are helpful tools in clinical practice for diagnosis, monitoring of treatment, and predicting prognosis in RA patients. However, further research is still required to investigate novel biomarkers for the pre-treatment selection of potentially responsive patients before starting therapy for a precision medicine in this area.

Outcomes and native renal recovery following simultaneous liver-kidney transplantation.

With the increase in patients having impaired renal function at liver transplant due to MELD, accurate predictors of posttransplant native renal recovery are needed to select candidates for simultaneous liver-kidney transplantation (SLK). Current UNOS guidelines rely on specific clinical criteria for SLK allocation. To examine these guidelines and other variables predicting nonrecovery, we analyzed 155 SLK recipients, focusing on a subset (n = 78) that had post-SLK native GFR (nGFR) determined by radionuclide renal scans. The 77 patients not having renal scans received a higher number of extended criteria donor organs and had worse posttransplant survival. Of the 78 renal scan patients, 31 met and 47 did not meet pre-SLK UNOS criteria. The UNOS criteria were more predictive than our institutional criteria for all nGFR recovery thresholds (20-40 mL/min), although at the most conservative cut-off (nGFR ≤ 20) it had low sensitivity (55.3%), specificity (75%), PPV (67.6%) and NPV (63.8%) for predicting post-SLK nonrecovery. On multivariate analysis, the only predictor of native renal nonrecovery (nGFR ≤ 20) was abnormal pre-SLK renal imaging (OR 3.85, CI 1.22-12.5). Our data support the need to refine SLK selection utilizing more definitive biomarkers and predictors of native renal recovery than current clinical criteria.

Working range of stimulus flux transduction determines dendrite size and relative number of pheromone component receptor neurons in moths.

We are proposing that the "relative" abundances of the differently tuned pheromone-component-responsive olfactory receptor neurons (ORNs) on insect antennae are not a result of natural selection working to maximize absolute sensitivity to individual pheromone components. Rather, relative abundances are a result of specifically tuned sensillum-plus-ORN units having been selected to accurately transduce and report to the antennal lobe the maximal ranges of molecular flux imparted by each pheromone component in every plume strand. To not reach saturating stimulus flux levels from the most concentrated plume strands of a pheromone blend, the dendritic surface area of the ORN type that is tuned to the most abundant component of a pheromone blend is increased in dendritic diameter in order to express a greater number of major pheromone component-specific odorant receptors. The increased ability of these enlarged dendrite, major component-tuned ORNs to accurately report very high flux of its component results in a larger working range of stimulus flux able to be accurately transduced by that type of ORN. However, the larger dendrite size and possibly other high-flux adjustments in titers of pheromone-binding proteins and degrading enzymes cause a decrease in absolute sensitivity to lower flux levels of the major component in lower concentration strands of the pheromone blend. In order to restore the ability of the whole-antenna major pheromone component-specific channel to accurately report to its glomerulus the abundance of the major component in lower concentration strands, the number of major component ORNs over the entire antenna is adjusted upward, creating a greater proportion of major component-tuned ORNs than those tuned to minor components. Pheromone blend balance reported by the whole-antennal major and minor component channels in low plume-flux strands is now restored, and the relative fluxes of the 2 components occurring in both low- and high-flux strands are thereby accurately reported to the component-specific glomeruli. Thus, we suggest that the 2 phenomena, dendrite size and relative numbers of differentially tuned ORNs are linked, and both are related to wide disparities in molecular flux ranges occurring for the more abundant and less abundant components in the pheromone blend plume strands.

Is childhood physical abuse associated with anxiety disorders among adults?

Several studies have examined the association between childhood physical abuse (CPA) and anxiety disorders with inconsistent results. In order to help clarify this relationship, we investigated the association between CPA and current anxiety disorders while controlling for the following groups of factors: (1) demographics; (2) family background; (3) current socioeconomic status (SES); (4) current stressors; and (5) current mood disorders. Data from the 2005 Canadian Community Health Survey were analyzed. The sample included 12,481 respondents from the Canadian provinces of Manitoba and Saskatchewan. The regional-level response rate was 84%. Fully 7.3% (n = 964) of respondents reported they had been physically abused as a child or adolescent by someone close to them and 4.4% (n = 540) reported they had been diagnosed with an anxiety disorder by a health professional. A significant association between CPA and anxiety disorders was found when controlling for demographic factors, family background, current SES and stressors (OR = 1.61; 95% CI = 1.25, 2.08). The odds of anxiety disorders declined to non-significance when further statistical adjustments were made for current mood disorders. The findings of this research suggest that the relationship between CPA and anxiety may be largely explained by co-morbid mood disorders.

The minor issue of electroconvulsive therapy.

ECT can be life-saving for patients with certain mental illnesses, such as severe depression, but that is no reason to allow ECT without informed consent. Nor is there general medical justification for the use of ECT on children, a practice in the United Kingdom that is out of control.

Early onset myasthenia gravis in a Malawian woman: Challenges in managing myasthenia gravis in a low-resource setting.

Myasthenia gravis is a rare autoimmune disease, which presents with ocular or generalised symptoms. Few publications describe its prevalence in African populations. We describe a young woman who was diagnosed with myasthenia gravis in a Malawian public hospital and outline the challenges encountered in managing this condition in a low-resource setting.

Healthcare utilization and costs among patients with psoriasis and psoriatic arthritis in the USA-a retrospective study of claims data from 2009 to 2020.

OBJECTIVES: To compare healthcare resource utilization and costs among patients with psoriasis, psoriatic arthritis (PsA), and a control group of patients without psoriasis and PsA in the USA. METHODS: The IBM® MarketScan® Commercial Database was used to identify three adult patient groups from 1/1/2009 through 4/30/2020: (1) Psoriasis: ≥ 2 diagnoses ≥ 30 days apart for psoriasis (no PsA diagnoses); (2) PsA: ≥ 2 diagnoses for PsA; (3) Control: no psoriasis or PsA diagnoses in their entire claims records. Patients with comorbid rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, or ulcerative colitis were excluded from the analyses. Controls were matched 1:1 to psoriasis and PsA patients based on age, gender, index year, and number of non-rheumatological comorbidities. Healthcare resource utilization and costs (in 2019 USD) were evaluated descriptively and through mixed models for five years of follow-up. RESULTS: A total of 142,531 psoriasis and 21,428 PsA patients were matched to the control group (N = 163,959). Annual all-cause healthcare costs per patient were $7,470, $11,062, and $29,742 for the control, psoriasis, and PsA groups, respectively. All-cause healthcare costs increased over time and were significantly greater among PsA vs. psoriasis (p < 0.0001) and the control groups (p < 0.0001). Across all categories of healthcare resources, utilization was greatest among patients with PsA and lowest in the control group. CONCLUSION: Annual healthcare costs and resource utilization were significantly higher with PsA compared with psoriasis and the control group, confirming the substantial economic burden of PsA. The cost disparity between these patient groups highlights a continued unmet medical need. Key Points • Patients with PsA incurred significantly greater healthcare resource utilization and costs than patients with psoriasis and patients without psoriasis and PsA. • Significantly greater costs and healthcare resource utilization were also observed among patients with psoriasis compared with patients without psoriasis and PsA.

Interleukin 1 of the central nervous system is produced by ameboid microglia.

By screening specific populations of rat brain cells, we found that ameboid microglia secrete an 18 kD peptide with IL-1 biological activity. The IL-1 activity released by microglia was found to be identical to rat macrophage IL-1 on fractionation by gel filtration and high pressure liquid anion-exchange chromatography, and it was neutralized by an antiserum specific for murine IL-1. When added to astroglia grown in culture, microglial IL-1 increased the cell number of five- to sevenfold, and increased astroglial incorporation of [3H]thymidine by three- to fivefold. We propose that the proliferation of astroglia in specific brain regions may be regulated by the signaled release of IL-1 from activated microglial cells.