Proxy evidence for state-dependence of climate sensitivity in the Eocene greenhouse.

Despite recent advances, the link between the evolution of atmospheric CO2 and climate during the Eocene greenhouse remains uncertain. In particular, modelling studies suggest that in order to achieve the global warmth that characterised the early Eocene, warmer climates must be more sensitive to CO2 forcing than colder climates. Here, we test this assertion in the geological record by combining a new high-resolution boron isotope-based CO2 record with novel estimates of Global Mean Temperature. We find that Equilibrium Climate Sensitivity (ECS) was indeed higher during the warmest intervals of the Eocene, agreeing well with recent model simulations, and declined through the Eocene as global climate cooled. These observations indicate that the canonical IPCC range of ECS (1.5 to 4.5 °C per doubling) is unlikely to be appropriate for high-CO2 warm climates of the past, and the state dependency of ECS may play an increasingly important role in determining the state of future climate as the Earth continues to warm.

Indian agriculture, air pollution, and public health in the age of COVID.

Emerging evidence supports the intuitive link between chronic health conditions associated with air pollution and the vulnerability of individuals and communities to COVID-19. Poor air quality already imposes a highly significant public health burden in Northwest India, with pollution levels spiking to hazardous levels in November and early December when rice crop residues are burned. The urgency of curtailing the COVID-19 pandemic and mitigating a potential resurgence later in the year provides even more justification for accelerating efforts to dramatically reduce open agricultural burning in India.

Managing taste and odour metabolite production in drinking water reservoirs: The importance of ammonium as a key nutrient trigger.

Taste and odour (T&O) compounds (most commonly 2-MIB and Geosmin) in drinking water are becoming an increasingly global problem for water management. Here, the trigger(s) for 2-MIB and Geosmin production were investigated in Plas Uchaf reservoir (North Wales, UK) with detailed water sample analysis between 2015 and 2016. Historical abstraction data from this reservoir and 4 reservoirs in Somerset (England, UK) were compared statistically using Self-Organising Map (SOM) analysis. In-reservoir measurements (2015-2016) revealed an 85% reduction in ammonium from the primary external loading source led to lower 2-MIB and Geosmin concentrations, with peak concentrations of 2-MIB declining from 60 to 21  ng l-1 and Geosmin declining from 140 to 18  ng l-1. No other measured water chemistry parameter showed a significant difference between years. The SOM results support the in-reservoir findings, revealing 2-MIB and Geosmin to be associated with high ammonium relative to nitrate for all 5 reservoirs. We conclude that ammonium is key for stimulating cyanobacterial productivity and production of T&O compounds. Whilst it is well understood that adequate availability of phosphorus is required for rapid growth in cyanobacteria, and hence should still be considered in management decisions, we suggest that monitoring sources and concentrations of ammonium is key for managing T&O outbreaks in drinking water reservoirs.

Early hatching enhances survival despite beneficial phenotypic effects of late-season developmental environments.

Seasonal shifts in environmental conditions provide predictable cues to which organisms can respond in adaptive ways. For example, seasonal changes in temperature can induce phenotypes at different times of the year that have season-specific fitness benefits. Here, we tested the hypothesis that embryo responses to seasonal changes in thermal environments are adaptively matched to the timing of reproduction (environmental-matching hypothesis). We collected eggs of the brown anole lizard (Anolis sagrei) from early and late seasons, and exposed them to early and late thermal regimes that mimic nest temperatures. After measuring offspring morphology and performance, we quantified their survival in the field. Females had higher fecundity, but produced smaller eggs, early in the season compared with late in the season. Late-season eggs exposed to late thermal regimes had relatively high survival, but early-season eggs exposed to early thermal regimes had similar survival rates to those exposed to mismatched conditions. Late-season nest temperatures and late-season eggs produced offspring that were relatively large and fast runners. However, despite phenotypic benefits of late-season conditions, early-season hatchlings had greater survival in the field. Our results do not fully support the environmental-matching hypothesis but suggest that selection favours seasonal shifts in reproductive investment of mothers (high early-season fecundity) over plastic responses of embryos to seasonal environmental changes.

Characterization of Intraocular Pressure Increases and Management Strategies Following Treatment With Fluocinolone Acetonide Intravitreal Implants in the FAME Trials.

BACKGROUND AND OBJECTIVE: To compare elevated intraocular pressure (IOP) management and outcomes among patients with diabetic macular edema who received fluocinolone acetonide (FAc) implants versus sham-control treatment and explore the prior ocular steroid exposure impact on IOP outcomes. PATIENTS AND METHODS: Best-corrected visual acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study charts or electronic VA testers. Goldmann applanation tonometry was used to measure IOP. RESULTS: Elevated IOP was more common in FAc-versus sham control-treated patients. Medication, and less often trabeculoplasty or surgery, was used to lower IOP without affecting VA outcomes. No patient treated with 0.2 µg/day FAc who received prior ocular steroid required IOP-lowering surgery. CONCLUSION: Elevated IOP may occur following FAc implant receipt; however, in the present study, it was manageable and did not impact vision outcomes. Patients previously treated with ocular steroid did not require IOP-lowering surgery following 0.2 µg/day FAc implant administration. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:426-435.].

Habitat- and season-specific temperatures affect phenotypic development of hatchling lizards.

Embryonic environments influence phenotypic development, but relatively few experiments have explored the effects of natural environmental variation. We incubated eggs of the lizard Anolis sagrei under conditions that mimicked natural spatial and temporal thermal variation to determine their effects on offspring morphology and performance. Incubation temperatures mimicked two microhabitats (open, shade) at two different times of the incubation season (April, July). Egg survival, incubation duration and offspring size were influenced by interactions between habitat- and season-specific nest temperatures, and locomotor performance was influenced primarily by temporal factors. These findings highlight the importance of spatial and temporal environmental variation in generating variation in fitness-related phenotypes.

Use of the Fluocinolone Acetonide Intravitreal Implant for the Treatment of Noninfectious Posterior Uveitis: 3-Year Results of a Randomized Clinical Trial in a Predominantly Asian Population.

INTRODUCTION: The fluocinolone acetonide (FA) intravitreal implant 0.59 mg (Retisert(®), Bausch + Lomb, Rochester, NY, USA) provides sustained release of FA directly to the vitreous cavity over a prolonged period of time. The purpose of this study was to evaluate the safety and efficacy of a 0.59- and 2.1-mg FA intravitreal implant in patients with noninfectious posterior uveitis. METHODS: A prospective, multicenter, randomized, double-masked, dose-controlled study was performed. Patients were randomized to the 0.59- or 2.1-mg FA implant surgically placed in the vitreous cavity through a pars plana incision and were evaluated at visits through 3 years. Patients with bilateral disease had the more severely affected eye implanted. Outcomes included uveitis recurrence rate, best-corrected visual acuity (BCVA), use of adjunctive therapy, and safety. RESULTS: A total of 239 patients, predominantly Asian, were implanted (n = 117, 0.59-mg implant; n = 122, 2.1-mg implant). Approximately 80% of patients had bilateral disease. Recurrence rates for implanted eyes decreased from 42.3% during the 1-year pre-implantation period to 25.9% during the 3-year post-implantation period (P = 0.0003) and increased for nonimplanted fellow eyes from 19.8 to 59.7% (P < 0.0001). More implanted eyes gained ≥3 lines of BCVA compared to nonimplanted fellow eyes (P ≤ 0.0046); and implanted eyes required less adjunctive systemic therapy and fewer periocular injections (P < 0.0001). Elevations of intraocular pressure (≥10 mm Hg) were frequent in implanted eyes (67.8%, 0.59-mg implant; 71.3%, 2.1-mg implant); nearly all (94.9%) phakic implanted eyes required cataract surgery. CONCLUSION: The FA intravitreal implant significantly reduced uveitis recurrence rates and led to improvements in visual acuity and reductions in adjunctive therapy. Lens clarity and intraocular pressure require monitoring.

Binocular training reduces amblyopic visual acuity impairment.

Amblyopia is the most common cause of monocular visual impairment. Patching, which is modestly effective, is the current treatment of amblyopia in children. There is no clinically approved treatment for adults. The present study is a clinical trial (non-sham controlled and non-randomized) that assessed the efficacy of binocular training for improvement of the visual acuity in children and adults with amblyopia. Twenty-two amblyopic subjects ranging in age from 5 to 73 (mean: 36.2) years for whom patching and/or surgical treatments did not correct their visual impairment completed an average of 14.5 sessions of binocular training over a period of 4 to 6 weeks. Random dot kinematograms were presented dichoptically to the two eyes and the participants' task was to identify the direction of motion of the targets. Mean visual acuity improvement was 0.34 LogMAR (range: 0.1-0.58 LogMAR) and was shown to persist 6 months following the cessation of binocular training. Our study provides results in a large number of patients that confirm the clinical effectiveness of binocular training as a treatment for amblyopia in improving visual acuity in both children and adults. Moreover, this study is the first to demonstrate that the improvements in visual function were maintained for 6 months in the absence of any additional treatment.

Fluocinolone acetonide intravitreal implant for diabetic macular edema: a 3-year multicenter, randomized, controlled clinical trial.

PURPOSE: We studied the 3-year efficacy and safety results of a 4-year study evaluating fluocinolone acetonide (FA) intravitreal implants in eyes with persistent or recurrent diabetic macular edema (DME). DESIGN: Prospective, evaluator-masked, controlled, multicenter clinical trial. PARTICIPANTS: We included 196 eyes with refractory DME. METHODS: Patients were randomized 2:1 to receive 0.59-mg FA implant (n = 127) or standard of care (SOC additional laser or observation; n = 69). The implant was inserted through a pars plana incision. Visits were scheduled on day 2, weeks 1, 3, 6, 12, and 26, and thereafter every 13 weeks through 3 years postimplantation. MAIN OUTCOME MEASURES: The primary efficacy outcome was ≥15-letter improvement in visual acuity (VA) at 6 months. Secondary outcomes included resolution of macular retinal thickening and Diabetic Retinopathy Severity Score (DRSS). Safety measures included incidence of adverse events (AEs). RESULTS: Overall, VA improved ≥3 lines in 16.8% of implanted eyes at 6 months (P=0.0012; SOC, 1.4%); in 16.4% at 1 year (P=0.1191; SOC, 8.1%); in 31.8% at 2 years (P=0.0016; SOC, 9.3%); and in 31.1% at 3 years (P=0.1566; SOC, 20.0%). The number of implanted eyes with no evidence of retinal thickening at the center of the macula was higher than SOC eyes at 6 months (P<0.0001), 1 year (P<0.0001; 72% vs 22%), 2 years (P=0.016), and 3 years (P=0.861). A higher rate of improvement and lower rate of decline in DRSS occurred in the implanted group versus the SOC group at 6 months (P=0.0006), 1 year (P=0.0016), 2 years (P=0.012), and 3 years (P=0.0207). Intraocular pressure (IOP) ≥30 mmHg was recorded in 61.4% of implanted eyes (SOC, 5.8%) at any time and 33.8% required surgery for ocular hypertension by 4 years. Of implanted phakic eyes, 91% (SOC, 20%) had cataract extraction by 4 years. CONCLUSIONS: The FA intravitreal implant met the primary and secondary outcomes, with significantly improved VA and DRSS and reduced DME. The most common AEs included cataract progression and elevated IOP. The 0.59-mg FA intravitreal implant may be an effective treatment for eyes with persistent or recurrent DME. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Literacy and science: each in the service of the other.

We use conceptual and empirical lenses to examine synergies between inquiry science and literacy teaching and learning of K-12 (kindergarten through high school) curriculum. We address two questions: (i) how can reading and writing be used as tools to support inquiry-based science, and (ii) how do reading and writing benefit when embedded in an inquiry-based science setting? After elaborating the theoretical and empirical support for integrated approaches, we discuss how to support their implementation in today's complicated curricular landscape.

Influences on self-evaluation during a clinical skills programme for nurses.

Education has moved from teacher to student-centred practices. Increasing emphasis is placed on 'life-long' learning in the context of a rapidly changing knowledge base. Self-evaluation is seen as one strategy to facilitate student-centred continuous professional development. The literature, however, suggests that learners' ability to self-assess is mixed, and little is known regarding how students perform self-assessment. This study focussed on senior nurses undertaking a scenario-based clinical skills course. Learners were asked to self-evaluate several times during the course. This research explored the influences on using the self-evaluation exercise. The study drew upon grounded theory methodology and was influenced by constructionist and postmodernist theories. Three methods of data collection were used: semi-structured interviews, observation of supervision sessions and recording of the numerical self-evaluation ratings. Multiple interviews with students (n = 14) and the educational supervisor (n = 1) were conducted. Thematic analysis and data collection were conducted iteratively. The study found that feeling confident and stating that confidence were not necessarily the same. Feeling confident was complex, influenced by changing perceptions of clinical skills and credibility. Changing frames of reference were used to judge feelings of confidence. Stating confidence appeared to be socially negotiated, influenced by social acceptability considerations such as modesty and the need to show progress over time. The discourses of empowerment and surveillance were influential and self-evaluation is discussed using Foucault's theory of governmentality, illustrating how learners can be both empowered and controlled through self-evaluation. Further consideration of the socially constructed nature of self-evaluations would benefit both educational practice and future research.

Copy number variations in three children with sudden infant death.

Sudden death of an infant is a devastating event that needs an explanation. When an explanation cannot be found, the case is labeled as sudden infant death syndrome or unclassified sudden infant death. The influence of genetic factors has been recognized for sudden infant death, but copy number variations (CNVs) as potential risk factors have not been evaluated yet. Twenty-seven families were enrolled in this study. The tissue specimens from deceased children were obtained and array-based comparative genomic hybridization (array-CGH) experiments were performed on the genomic DNA isolated from these specimens using Agilent Technologies Custom 4 x 44K arrays. Quantitative polymerase chain reaction experiments were performed to confirm the overlapping duplication and deletion region in two different cases. A de novo CNV is detected in 3 of 27 cases (11%). In case 1, an approximately 3-Mb (chr 8: 143,211,215-qter) duplication on 8q24.3-qter and a 4.4-Mb deletion on the 22q13.3-qter (chr 22: 45,047,068-qter) were detected. Subtelomeric chromosome analysis of the father and the surviving sibling of case 1 showed a balanced reciprocal translocation, 46,XY,t(8;22)(q24.3;q13.3). A 240-kb (chr 6: 26,139,810-26,380,787) duplication and a 1.9-Mb deletion (chr 6: 26,085,971-27,966,150) at chromosome 6p22 were found in cases 2 and 3, respectively. Array-CGH and conventional cytogenetic studies did not reveal the observed CNVs in the parents and the siblings of cases 2 and 3. The detected CNVs in cases 2 and 3 encompassed several genes including the major histone cluster genes. Array-CGH analysis may be beneficial during the investigations after sudden infant death.

Bilateral central retinal artery occlusion in a patient with acute pancreatitis.

PURPOSE: To illustrate a case of bilateral simultaneous central retinal artery occlusion in a patient with acute pancreatitis. METHODS: This patient presented to the emergency room with a 4-day history of acute painless bilateral loss of vision and was then immediately referred to the on-call ophthalmologist. PATIENT: This patient is a 47-year-old white man with a chronic history of alcohol abuse. RESULTS: Laboratory workup and computed tomography abdominal imaging were diagnostic of acute pancreatitis. DISCUSSION: It is postulated that the resultant complement activation with subsequent leukoembolization along with the combined effect of other variables led to microvascular damage resulting in bilateral central retinal artery occlusion.

Treatment of posterior uveitis with a fluocinolone acetonide implant: three-year clinical trial results.

OBJECTIVES: To evaluate the safety and efficacy of 0.59-mg and 2.1-mg fluocinolone acetonide (FA) intravitreous implants in noninfectious posterior uveitis. DESIGN: A 3-year, multicenter, randomized, historically controlled trial of the 0.59-mg FA intravitreous implant in 110 patients and the 2.1-mg FA intravitreous implant in 168 patients. MAIN OUTCOME MEASURES: Recurrence rate, vision, and complications. RESULTS: Uveitis recurrence was reduced in implanted eyes from 62% (during the 1-year preimplantation period) to 4%, 10%, and 20% during the 1-, 2-, and 3-year postimplantation periods, respectively, for the 0.59-mg dose group (P < .01) and from 58% to 7%, 17%, and 41%, respectively, for the 2.1-mg dose group (P < .01). More implanted eyes than nonimplanted eyes had improved visual acuity (P < .01). Implanted eyes had higher incidences of intraocular pressure elevation (> or = 10 mm Hg) than nonimplanted eyes (P < .01), and glaucoma surgery was required in 40% of implanted eyes vs 2% of nonimplanted eyes (P < .01). Cataracts were extracted in 93% of phakic implanted eyes vs 20% of phakic nonimplanted eyes (P < .01). CONCLUSIONS: The FA implant significantly reduced uveitis recurrence and improved or stabilized visual acuity in subjects with noninfectious posterior uveitis. Most subjects required cataract extraction, and a significant proportion required intraocular pressure-lowering surgery. APPLICATION TO CLINICAL PRACTICE: The FA implant provides an alternative therapy for prolonged control of inflammation in noninfectious posterior uveitis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00407082.

Diagnostic and therapeutic performance of video-assisted thoracoscopic surgery (VATS) in investigation and management of pleural exudates.

INTRODUCTION: Video-assisted thoracoscopic surgery (VATS) is the gold standard investigation for diagnosis of pleural exudates. It is invasive and it is important to ensure that it is performed to acceptable national standards. We assumed that VATS empyema fluid culture would not contribute further to microbiological diagnosis in referred culture-negative empyemas. PATIENTS AND METHODS: Eighty-six consecutive external referrals for VATS for diagnosis of a cytology-negative pleural exudate (or for further management of the exudate) were studied retrospectively. Diagnostic yield, pleurodesis efficacy and complications were compared to national standards and good practice recommendations. VATS empyema fluid microbiological culture results were compared to pre-VATS empyema fluid culture results. RESULTS: VATS was performed well within national standards with a diagnostic yield of 82.3% for cytology-negative exudates, 100% pleurodesis efficacy, 5.8% postoperative fever, with only one significant complication (1.2% rate) and no deaths. Compliance with good practice pleural fluid documentation points was greater than 70%. VATS empyema fluid culture positivity (84.6%) was significantly higher than pre-VATS fluid culture (35%). CONCLUSIONS: VATS was performed to acceptable standards. These data confirm the utility and safety of VATS in the right context but also suggest the potential diagnostic utility of VATS empyema fluid culture. Further studies are required to investigate this latter possibility further.

Real-time three-dimensional myocardial contrast echocardiography: is it clinically feasible?

AIMS: Real-time 3D echocardiography (RT3DE) and 2D low mechanical index (LMI), contrast specific, myocardial perfusion imaging are now both accepted techniques. We evaluated the feasibility of an RT3DE LMI implementation in unselected patients. METHODS AND RESULTS: Forty-six patients undergoing contrast enhanced dobutamine stress echo were imaged with novel 3D LMI power modulation software. All patients underwent contrast enhanced 2D and RT3DE acquisitions, in left ventricular opacification (LVO), and LMI perfusion modes. The data sets were evaluated segmentally for wall motion (WM) and myocardial contrast enhancement. Of the 736 evaluated segments, WM could be assessed in 726 (98.6%) of the 2D and 708 (96.2%) 3D segments (P = 0.007). Perfusion could be assessed in 721 (98%) of 2D and 701 (95.2%) of 3D segments (P = 0.006). Six hundred and sixty-one segments had normal WM and thickening in 2D and of these RT3DE demonstrated normal myocardial opacification in 77.2% of basal, 85% of mid, and 91.8% of apical segments. Thirty-four segments were akinetic, with no evidence of perfusion in 2D, and of these RT3DE revealed a perfusion defect in 31 (91%, P = NS). CONCLUSION: LMI RT3DE evaluation of myocardial perfusion is feasible in most segments. It has the potential to accurately locate and possibly quantify perfusion defects.