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BACKGROUND: The etiology of endometriosis is not well understood. Limited evidence suggests that dietary factors influence risk, but prospective data related to carbohydrate, fiber, and gluten consumption are scarce. Despite this, recommendations concerning fiber, gluten intake, and endometriosis are pervasive in the lay literature. OBJECTIVES: We aimed to investigate the associations of carbohydrate quality [glycemic index (GI) and glycemic load (GL)], fiber intake (total, legume, vegetable, cruciferous vegetable, fruit, cereal), and gluten intake with incident laparoscopically confirmed endometriosis. METHODS: This was a prospective cohort study using data collected from 81,961 premenopausal women in the Nurses’ Health Study II (mean age = 36 y in 1991). Diet was assessed with a validated FFQ every 4 y. Cox proportional hazards models were used to calculate rate ratios (RRs) and 95% CIs. RESULTS: A total of 3810 incident cases of laparoscopically confirmed endometriosis were reported over 24 y of follow-up. Women in the highest quintile of GI had 12% (95% CI: 1.01, 1.23; P(trend) = 0.03) higher risk of endometriosis diagnosis than those in the lowest quintile. Total vegetable and cruciferous vegetable fiber intakes were also associated with higher risk (highest compared with lowest quintile RR: 1.13; 95% CI: 1.02, 1.24; P(trend) = 0.004 and RR: 1.17; 95% CI: 1.06, 1.29; P(trend) = 0.02, respectively). Higher intake of fruit fiber was associated with lower risk of endometriosis but the association was not significant after adjusting for the Alternative Healthy Eating Index. Gluten intake was also associated with lower risk (highest compared with lowest quintile RR: 0.91; 95% CI: 0.80, 1.02; P(trend) = 0.01), but these results were not consistent in direction nor statistical significance across sensitivity analyses. No association was observed for GL or total, legume, or cereal fiber intake. CONCLUSIONS: Our findings suggest that carbohydrate quality and specific types of fiber—total vegetable and cruciferous vegetable fiber—are associated with endometriosis diagnosis in premenopausal women. These results also indicate it is unlikely that gluten intake is a strong factor in the etiology or symptomatology of endometriosis.

Background: There are no established methods for pancreatic cancer (PAC) screening, but the NCI and the Pancreatic Cancer Action Network (PanCAN) are investigating risk-based screening strategies in patients with new-onset diabetes (NOD), a group with elevated PAC risk. Preliminary estimates of the cost-effectiveness of these strategies can provide insights about potential value and inform supplemental data collection. Using data from the Enriching New-Onset Diabetes for Pancreatic Cancer (END-PAC) risk model validation study, we assessed the potential value of CT screening for PAC in those determined to be at elevated risk, as is being done in a planned PanCAN Early Detection Initiative trial. Methods: We created an integrated decision tree and Markov state-transition model to assess the cost-effectiveness of PAC screening in patients aged ≥50 years with NOD using CT imaging versus no screening. PAC prevalence, sensitivity, and specificity were derived from the END-PAC validation study. PAC stage distribution in the no-screening strategy and PAC survival were derived from the SEER program. Background mortality for patients with diabetes, screening and cancer care expenditure, and health state utilities were derived from the literature. Life-years (LYs), quality-adjusted LYs (QALYs), and costs were tracked over a lifetime horizon and discounted at 3% per year. Results are presented in 2020 US dollars, and we took a limited US healthcare perspective. Results: In the base case, screening resulted in 0.0055 more LYs, 0.0045 more QALYs, and $293 in additional expenditures for a cost per QALY gained of $65,076. In probabilistic analyses, screening resulted in a cost per QALY gained of 25% of screen-detected PAC cases needed to be resectable for the cost per QALY gained with screening to be Conclusions: We found that risk-based PAC screening in patients with NOD is likely to be cost-effective in the United States if even a modest fraction (>25%) of screen-detected patients with PAC are resectable. Future studies should reassess the value of this intervention once clinical trial data become available.

Synopsis Genome size varies ∼100,000-fold across eukaryotes and has long been hypothesized to be influenced by metamorphosis in animals. Transposable element accumulation has been identified as a major driver of increase, but the nature of constraints limiting the size of genomes has remained unclear, even as traits such as cell size and rate of development co-vary strongly with genome size. Salamanders, which possess diverse metamorphic and non-metamorphic life histories, join the lungfish in having the largest vertebrate genomes—3 to 40 times that of humans—as well as the largest range of variation in genome size. We tested 13 biologically-inspired hypotheses exploring how the form of metamorphosis imposes varying constraints on genome expansion in a broadly representative phylogeny containing 118 species of salamanders. We show that metamorphosis during which animals undergo the most extensive and synchronous remodeling imposes the most severe constraint against genome expansion, with the severity of constraint decreasing with reduced extent and synchronicity of remodeling. More generally, our work demonstrates the potential for broader interpretation of phylogenetic comparative analysis in exploring the balance of multiple evolutionary pressures shaping phenotypic evolution.

Narrative electronic prescribing instructions (NEPIs) are text that convey information on the administration or co-administration of a drug as directed by a prescriber. For researchers, NEPIs have the potential to advance our understanding of the risks and benefits of medications in populations; however, due to their unstructured nature, they are not often utilized. The goal of this scoping review was to evaluate how NEPIs are currently employed in research, identify opportunities and challenges for their broader application, and provide recommendations on their future use. The scoping review comprised a comprehensive literature review and a survey of key stakeholders. From the literature review, we identified 33 primary articles that described the use of NEPIs. The majority of articles (n = 19) identified issues with the quality of information in NEPIs compared with structured prescribing information; nine articles described the development of novel algorithms that performed well in extracting information from NEPIs, and five described the used of manual or simpler algorithms to extract prescribing information from NEPIs. A survey of 19 stakeholders indicated concerns for the quality of information in NEPIs and called for standardization of NEPIs to reduce data variability/errors. Nevertheless, stakeholders believed NEPIs present an opportunity to identify prescriber's intent for the prescription and to study temporal treatment patterns. In summary, NEPIs hold much promise for advancing the field of pharmacoepidemiology. Researchers should take advantage of addressing important questions that can be uniquely answered with NEPIs, but exercise caution when using this information and carefully consider the quality of the data.

The inner $\sim$200 pc region of the Galaxy contains a 4 million M$_{\odot}$ supermassive black hole (SMBH), significant quantities of molecular gas, and star formation and cosmic ray energy densities that are roughly two orders of magnitude higher than the corresponding levels in the Galactic disk. At a distance of only 8.2 kpc, the region presents astronomers with a unique opportunity to study a diverse range of energetic astrophysical phenomena, from stellar objects in extreme environments, to the SMBH and star-formation driven feedback processes that are known to influence the evolution of galaxies as a whole. We present a new survey of the Galactic center conducted with the South African MeerKAT radio telescope. Radio imaging offers a view that is unaffected by the large quantities of dust that obscure the region at other wavelengths, and a scene of striking complexity is revealed. We produce total intensity and spectral index mosaics of the region from 20 pointings (144 hours on-target in total), covering 6.5 square degrees with an angular resolution of 4$"$,at a central frequency of 1.28 GHz. Many new features are revealed for the first time due to a combination of MeerKAT's high sensitivity, exceptional $u,v$-plane coverage, and geographical vantage point. We highlight some initial survey results, including new supernova remnant candidates, many new non-thermal filament complexes, and enhanced views of the Radio Arc Bubble, Sgr A and Sgr B regions. This project is a SARAO public legacy survey, and the image products are made available with this article., Comment: 29 pages, 15 figures, 3 tables, accepted for publication in the The Astrophysical Journal. Replacement arXiv version with higher quality figures

Background Central nervous system (CNS)-active medication use is an important modifiable risk factor for falls in older adults. A fall-related injury should prompt providers to evaluate and reduce CNS-active medications to prevent recurrent falls. We evaluated change in CNS-active medications up to 12 months following a fall-related injury in community-dwelling older adults compared with a matched cohort without fall-related injury. Methods Participants were from the Adult Changes in Thought study conducted at Kaiser Permanente Washington. Fall-related injury codes between 1994 and 2014 defined index encounters in participants with no evidence of such injuries in the preceding year. We matched each fall-related injury index encounter with up to five randomly selected clinical encounters from participants without injury. Using automated pharmacy data, we estimated the average change in CNS-active medication use at 3, 6, and 12 months post-index according to the presence or absence of CNS-active medication use before index. Results One thousand five hundred sixteen participants with fall-related injury index encounters (449 CNS-active users, 1067 nonusers) were matched to 7014 index encounters from people without fall-related injuries (1751 users, 5236 nonusers). Among CNS-active users at the index encounter, those with fall-related injury had an average decrease in standard daily doses (SDDs) at 12 months (-0.43; 95% CI: -0.63 to -0.23), and those without injury had a greater (p = 0.047) average decrease (-0.66; 95% CI: -0.78 to -0.55). Among nonusers at index, those with fall-related injury had a smaller increase than those without injury (+0.17, 95% CI: +0.13 to +0.21, vs. +0.24, 95% CI: +0.20 to +0.28, p = 0.005). Conclusions The differences in CNS-active medication use change over 12 months between those with and without fall-related injury were small and unlikely to be clinically significant. These results suggest that fall risk-increasing drug use is not reduced following a fall-related injury, thus opportunities exist to reduce CNS-active medications, a potentially modifiable risk factor for falls.

Background/Introduction Advancements in balloon-expandable transcatheter heart valves (THV) have improved outcomes in transcatheter aortic valve implantation (TAVI). The most recent iteration, the SAPIEN 3 Ultra THV, offers a taller paravalvular skirt which has demonstrated similar short-term outcomes while reducing mild paravalvular leak in high- and intermediate-risk patients. Purpose We sought to describe a real-world experience comparing short-term outcomes in the SAPIEN 3 THV to the SAPIEN 3 Ultra THV in patients across the risk spectrum (including low-risk). Methods We conducted a retrospective, observational study of patients who underwent TAVI using either the SAPIEN 3 or SAPIEN 3 Ultra THV between 2019–2020. In-hospital, 30-day and 1-year Valve Academic Research Consortium-2–defined outcomes were examined. Results We screened a total of 457 patients who underwent TAVI at our institution between 2019–2020. Included were 254 patients who received either the SAPIEN 3 THV or the SAPIEN 3 Ultra THV. Baseline clinical characteristics were similar in both cohorts (Table 1). Procedural success was similar in both cohorts (97.2% vs. 97.3%; p=1.ehab724.1647) with similar rates of >mild paravalvular leak (7.7% vs. 10.7%; p=0.3796). Mortality and rates of stroke were extremely low and similar in both cohorts at 30 days and 1 year (Table 2). There was a trend towards lower rates of permanent pacemaker implantation in the SAPIEN 3 Ultra cohort (In-Hospital: 9.2% vs.4.5%, p=0.2177; 30-Day: 11.3% vs.4.5%, p=0.0658; 1-Year: 12.7% 5.4%, p=0.0536). Conclusions In this real-world analysis of contemporary TAVI patients across the risk spectrum, the SAPIEN 3 Ultra THV demonstrated excellent short-term outcomes comparable to the SAPIEN 3 THV with a trend towards lower rates of permanent pacemaker implantation. Funding Acknowledgement Type of funding sources: None.

Disease-free survival (DFS) in early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer is significantly greater with the addition of neratinib after adjuvant trastuzumab versus no additional therapy. However, it remains uncertain whether these survival gains represent good value for the money, given the substantial cost of neratinib.To evaluate clinical and economic implications of adding neratinib after adjuvant trastuzumab based on results from the phase III ExteNET trial.A 3-state Markov model was developed to estimate the cost-effectiveness of neratinib for women with early-stage (I-III) HER2-positive breast cancer. Five-year recurrence rates were derived from the ExteNET trial. Mortality and recurrence rates after 5 years were derived from the HERceptin Adjuvant (HERA) trial. Outcomes included life-years, quality-adjusted life-years (QALYs), and direct medical expenditures. The analysis was performed from a payer perspective over a lifetime horizon. One-way sensitivity and probabilistic analyses were conducted to evaluate uncertainty.Total cost of neratinib following adjuvant trastuzumab was $317,619 versus $152,812 for adjuvant trastuzumab alone. A gain of 0.4 QALYs (15.7 vs. 15.3) and 0.1 years of projected life expectancy (18.3 vs. 18.2) favored neratinib after trastuzumab versus trastuzumab alone. The neratinib cost per QALY gained was $416,106. At standard willingness-to-pay thresholds of $50,000, $100,000, and $200,000 per QALY gained, neratinib has a probability of 2.8%, 16.7%, and 33.9% of cost-effectiveness, respectively. The cost per QALY gained in a scenario analysis only including patients with hormone-receptor positive disease was $275,311.Based on 5-year data from ExteNET, neratinib following adjuvant trastuzumab is not projected to be cost-effective, even among those patients shown to derive the greatest clinical benefit. Future analyses should reassess the cost-effectiveness associated with neratinib treatment as trial data mature.No outside funding supported this study. Roth reports consulting fees from Genentech. Steuten reports grants from AstraZeneca, EMD Serono, and Genomic Health, along with personal fees from Agendia, unrelated to this study. The other authors have no conflicts of interest in connection with this study.

Leishmaniasis is broadly classified into three types: cutaneous, mucocutaneous and visceral. The visceral form is most dangerous and can result in death. Although leishmaniasis is an ancient disease, its treatment is still challenging. Several drugs, differing in their cost, toxicity, treatment duration and emergence of drug resistance, are used for different types of leishmaniasis. To overcome these limitations, the search for newer drugs and other treatments continues. In this article, we discuss conventional drugs, other treatments, including newer options such as immunotherapy and immunochemotherapy, and future prospects for leishmaniasis treatment.

We present experiments and simulations of high energy mid-infrared laser-matter applications, including near-critical density laser wakefield acceleration, detection of ultralow electron densities from radiation or strong-field ionization, and novel mechanisms for nonlinear infrared self-guiding.

Aims. The Spectrometer Telescope for Imaging X-rays (STIX) on Solar Orbiter is a hard X-ray imaging spectrometer, which covers the energy range from 4 to 150 keV. STIX observes hard X-ray bremsstrahlung emissions from solar flares and therefore provides diagnostics of the hottest (⪆10 MK) flare plasma while quantifying the location, spectrum, and energy content of flare-accelerated nonthermal electrons. Methods. To accomplish this, STIX applies an indirect bigrid Fourier imaging technique using a set of tungsten grids (at pitches from 0.038 to 1 mm) in front of 32 coarsely pixelated CdTe detectors to provide information on angular scales from 7 to 180 arcsec with 1 keV energy resolution (at 6 keV). The imaging concept of STIX has intrinsically low telemetry and it is therefore well-suited to the limited resources available to the Solar Orbiter payload. To further reduce the downlinked data volume, STIX data are binned on board into 32 selectable energy bins and dynamically-adjusted time bins with a typical duration of 1 s during flares. Results. Through hard X-ray diagnostics, STIX provides critical information for understanding the acceleration of electrons at the Sun and their transport into interplanetary space and for determining the magnetic connection of Solar Orbiter back to the Sun. In this way, STIX serves to link Solar Orbiter’s remote and in-situ measurements.

BACKGROUND: Linked birth certificate–hospital discharge records are a valuable resource for examining pregnancy outcomes among women with disability conditions. Few studies relying on these data have been able to assess the accuracy of identification of pre-existing disability conditions. We assessed the accuracy of International Classification of Diseases version 9 (ICD9) codes for identifying selected physical, sensory, and intellectual conditions that may result in disability. As ICD9 codes were utilized until recently in most states, this information is useful to inform analyses with these records. METHODS: We reviewed 280 of 311 (90%) medical records of pregnant women with disabilities based on ICD9 codes and 390 of 8,337 (5%) records of pregnant women without disabilities who had deliveries at a large university medical center. We estimated sensitivity, specificity, and positive predictive values (PPV) using the medical record as gold standard. We adjusted for verification bias using inverse probability weighting and imputation. RESULTS: The estimated sensitivity of ICD9 codes to identify women with disabilities with deliveries 2009–2012 was 44%; PPV was 98%, improving over time. Although sensitivity was

MeerKAT's large number of antennas, spanning 8 km with a densely packed 1 km core, create a powerful instrument for wide-area surveys, with high sensitivity over a wide range of angular scales. The MeerKAT Galaxy Cluster Legacy Survey (MGCLS) is a programme of long-track MeerKAT L-band (900-1670 MHz) observations of 115 galaxy clusters, observed for $\sim$6-10 hours each in full polarisation. The first legacy product data release (DR1), made available with this paper, includes the MeerKAT visibilities, basic image cubes at $\sim$8" resolution, and enhanced spectral and polarisation image cubes at $\sim$8" and 15" resolutions. Typical sensitivities for the full-resolution MGCLS image products are $\sim$3-5 {\mu}Jy/beam. The basic cubes are full-field and span 4 deg^2. The enhanced products consist of the inner 1.44 deg^2 field of view, corrected for the primary beam. The survey is fully sensitive to structures up to $\sim$10' scales and the wide bandwidth allows spectral and Faraday rotation mapping. HI mapping at 209 kHz resolution can be done at $0, Comment: 43 pages, 33 figures, 6 tables. Accepted for publication in Astronomy and Astrophysics

Background: Few studies have reported on interventions to alleviate financial toxicity in patients with cancer. We developed a financial navigation program in collaboration with our partners, Consumer Education and Training Services (CENTS) and Patient Advocate Foundation (PAF), to improve patient knowledge about treatment costs, provide financial counseling, and to help manage out-of-pocket expenses. We conducted a pilot study to assess the feasibility and impact of this program. Methods: Patients with cancer received a financial education course followed by monthly contact with a CENTS financial counselor and a PAF case manager for 6 months. We measured program adherence, self-reported financial burden and anxiety, program satisfaction, and type of assistance provided. Results: Thirty-four patients (median age, 60.5 years) were consented (85% white and 50% commercially insured). Debt, income declines, and loans were reported by 55%, 55%, and 30% of patients, respectively. CENTS counselors assisted most often with budgeting, retirement planning, and medical bill questions. PAF case managers assisted with applications for appropriate insurance coverage, cost of living issues (eg, housing, transportation), and disability applications. High financial burden and anxiety about costs (4 or 5 on a Likert scale) were reported at baseline by 37% and 47% of patients, respectively. Anxiety about costs decreased over time in 33% of patients, whereas self-reported financial burden did not substantially change. Conclusion: Implementing an oncology financial navigation program is feasible, provides concrete assistance in navigating the cost of care, and mitigates anxiety about costs in a subset of patients. Future work will focus on measuring the program’s impact on financial and clinical outcomes.

OBJECTIVES: Evidence suggests use of proton pump inhibitors (PPIs) and H(2) blockers may provoke disease flares in individuals with established inflammatory bowel disease (IBD); however, there are no studies investigating the relationship of these medications with risk of developing pediatric IBD. The hypothesis was that use of acid suppression therapy in children might be associated with development of pediatric IBD. METHODS: This was a nested case-control study of 285 Kaiser Permanente Northern California members, age ≤21 years diagnosed with IBD from 1996 to 2016. Four controls without IBD were matched to each case on age, race, and membership status at the case's index date. Disease risk scores (DRS) were computed for each subject. Odds ratios and 95% confidence intervals were calculated by using conditional logistic regression models adjusted for DRS. RESULTS: The children's mean age was 15.1 ± 2.6 years and 49.5% were female. Six cases (n = 3 Crohn's disease [CD], n = 3 ulcerative colitis [UC]) and 6 controls were prescribed PPIs and 10 cases (n = 7 CD, n = 3 UC) and 28 controls were prescribed H2 blockers. The OR for the association of at least 1 PPI or H(2) blocker prescription with subsequent IBD was 3.6 (95% CI, 1.1–11.7) for PPIs and 1.6 (95% CI, 0.7–3.7) for H(2) blockers. CONCLUSIONS: Early-life PPI use appears to be associated with subsequent IBD risk. These findings have implications for clinical treatment of children with gastrointestinal symptoms and warrant further investigation in a larger cohort.

This paper studies the energy dissipation of nonthermal electrons in the chromospheric flare ribbons during the peak time of a Geostationary Operational Environmental Satellite X-class flare (SOL2011-09-06) using desaturated Solar Dynamics Observatory/Atmospheric Imaging Assembly extreme-ultraviolet (EUV) narrow-band images. The temperature distribution in emission measure, called the differential emission measure (DEM), derived from the EUV fluxes from the flare ribbons shows an increase in the emission measure up to a temperature around 9 × 106 K, followed by a steep decline at higher temperatures. In contrast, the flare loop reaches temperatures up to 27 × 106 K. This result is in agreement with previously reported single-temperature measurements using soft X-ray filter images, as well as DEM distributions reported for smaller flares obtained from EUV line observations. The main difference between small and large flares appears to be an increased emission measure in the flare ribbons, while the ribbon peak temperature is similar for all flares. This is different from the flare loop temperatures, where the hottest temperatures occur in the largest flares. However, the physically relevant quantity for energy dissipation, the energy content of the heated plasma as a function of temperature, does not need to peak at the same temperature as the DEM. The poorly constrained source thickness in radial extent of the flare ribbons has a significant impact on the shape of the differential thermal energy distribution. In particular, if the highest temperatures occur over a wide radial extent as “evaporating” plasma starts expending, the largest amount of energy could potentially be hidden above the peak temperature of the DEM.

7017 Background: There are no established methods for pancreatic cancer (PC) screening, but the National Cancer Institute and the Pancreatic Cancer Action Network (PanCAN) are investigating risk-based screening strategies in new-onset diabetes (NOD)—a group with elevated PC risk. Preliminary estimates of the cost-effectiveness of these strategies can provide insights about potential value and inform supplemental data collection. Using data from the Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) risk model validation study, we assessed the potential value of CT screening for PC in those determined to be at elevated PC risk, as is being done in a planned PanCAN Early Detection Initiative (EDI) trial. Methods: We created an integrated decision tree and Markov state-transition model to assess the cost-effectiveness of screening those age ≥50 and with NOD for PC using CT imaging vs. no screening. PC prevalence, sensitivity, and specificity were derived from the ENDPAC validation study. PC stage distribution in the no screening strategy and PC survival were derived from SEER. Background mortality for diabetics, screening and cancer care expenditure, and health state utilities were derived from the literature. The base case assumed 40% of screen-detected PC cases were resectable, and a threshold analysis explored the fraction required for screening to be 25% of screen-detected cases needed to be resectable for the cost per QALY gained with screening to be 25%) of screen-detected cases are resectable. Future studies should reassess the value of this intervention once PanCAN EDI data become available. [Table: see text]

Summary VRC-HIVMAB060-00-AB (VRC01) is a broadly neutralizing HIV-1 monoclonal antibody (mAb) isolated from the B cells of an HIV-infected patient. It is directed against the HIV-1 CD4 binding site and is capable of potently neutralizing the majority of diverse HIV-1 strains. This Phase I dose-escalation study in healthy adults was conducted at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA). Primary objectives were the safety, tolerability and pharmacokinetics (PK) of VRC01 intravenous (i.v.) infusion at 5, 20 or 40 mg/kg, given either once (20 mg/kg) or twice 28 days apart (all doses), and of subcutaneous (s.c.) delivery at 5 mg/kg compared to s.c. placebo given twice, 28 days apart. Cumulatively, 28 subjects received 43 VRC01 and nine received placebo administrations. There were no serious adverse events or dose-limiting toxicities. Mean 28-day serum trough concentrations after the first infusion were 35 and 57 μg/ml for groups infused with 20 mg/kg (n = 8) and 40 mg/kg (n = 5) doses, respectively. Mean 28-day trough concentrations after the second infusion were 56 and 89 μg/ml for the same two doses. Over the 5–40 mg/kg i.v. dose range (n = 18), the clearance was 0·016 l/h and terminal half-life was 15 days. After infusion VRC01 retained expected neutralizing activity in serum, and anti-VRC01 antibody responses were not detected. The human monoclonal antibody (mAb) VRC01 was well tolerated when delivered i.v. or s.c. The mAb demonstrated expected half-life and pharmacokinetics for a human immunoglobulin G. The safety and PK results support and inform VRC01 dosing schedules for planning HIV-1 prevention efficacy studies.

Subtropical marine stratus clouds regulate coastal and global climate, but future trends in these clouds are uncertain. In coastal Southern California (CSCA), interannual variations in summer stratus cloud occurrence are spatially coherent across 24 airfields and dictated by positive relationships with stability above the marine boundary layer (MBL) and MBL height. Trends, however, have been spatially variable since records began in the mid-1900s due to differences in nighttime warming. Among CSCA airfields, differences in nighttime warming, but not daytime warming, are strongly and positively related to fraction of nearby urban cover, consistent with an urban heat island effect. Nighttime warming raises the near-surface dew point depression, which lifts the altitude of condensation and cloud base height, thereby reducing fog frequency. Continued urban warming, rising cloud base heights, and associated effects on energy and water balance would profoundly impact ecological and human systems in highly populated and ecologically diverse CSCA.

Six decades of observations at 20 coastal airports, from Alaska to southern California, reveal coherent interannual to interdecadal variation of coastal low cloudiness (CLC) from summer to summer over this broad region. The leading mode of CLC variability represents coherent variation, accounting for nearly 40% of the total CLC variance spanning 1950–2012. This leading mode and the majority of individual airports exhibit decreased low cloudiness from the earlier to the later part of the record. Exploring climatic controls on CLC, we identify North Pacific Sea Surface Temperature anomalies, largely in the form of the Pacific Decadal Oscillation (PDO) as well correlated with, and evidently helping to organize, the coherent patterns of summer coastal cloud variability. Links from the PDO to summer CLC appear a few months in advance of the summer. These associations hold up consistently in interannual and interdecadal frequencies.

6625 Background: Neratinib after adjuvant trastuzumab significantly improves disease-free survival (DFS) in human epidermal growth factor receptor 2-postiive (HER2+) breast cancer, but the median absolute DFS gain is only 1.3 months. There has been much controversy in the clinical and lay media as to whether the substantial cost of neratinib is justified by its effects, including a prominent ASCO Post article from Dr. Vogl about a year ago. We performed a cost-utility analysis to formally assess the value of adding neratinib based on Phase III ExteNET trial results. Methods: We developed a Markov state-transition model to assess the value of neratinib in Stage I-III HER2+ breast cancer. Five-year recurrence rates were derived from ExteNet. Mortality and recurrence rates after 5 years were derived from the HERceptin Adjuvant (HERA) trial. Costs were derived from wholesale acquisition costs and peer-reviewed literature. Health state utilities were derived from ExteNET and prior publications. Outcomes included life years (LY), quality-adjusted life years (QALYs), direct medical expenditures, and cost per QALY gained. The analysis took a payer perspective over a lifetime horizon and results were discounted at 3% per year. One-way and probabilistic analyses were conducted to evaluate uncertainty. As neratinib conferred more clinical benefit in hormone receptor-positive (HR+) disease, we also assessed value in that specific subgroup. Results: Base case results are presented in Table. At typical U.S. willingness to pay thresholds of $100,000 and $150,000 per QALY gained, neratinib had 16.7% and 27.2%, probabilities of cost-effectiveness, respectively. In the HR+ subgroup, neratinib had a cost of $275,311 per QALY gained (19.9% & 31.2% probability of cost-effectiveness at $100,000 & $150,000 per QALY). Conclusions: In the first independent assessment of the value of neratinib after adjuvant trastuzumab, neratinib is not projected to be cost-effective, even among patients who derived the most clinical benefit. Future analyses should reassess the cost-effectiveness of neratinib treatment as trial data mature. Base case results. [Table: see text]

Aim. To assess the effects of amlodipine therapy on quality of life (QoL) parameters among patients with different stages of essential arterial hypertension (EAH). Material and methods. In 97 EAH patients, aged 30-60 years, QoL parameters were assessed before and after amlodipine therapy. Results. In EAH patients, baseline QoL levels were relatively low, especially for the domains of general health, vitality, and mental health. Amlodipine monotherapy improved the physical QoL component, without any clear beneficial impact on mental wellbeing. The largest effect of amlodipine monotherapy on QoL parameters was observed among Stage I EAH patients. It might be the case that this therapy decreases QoL in Stage II and especially Stage III EAH patients, negatively affecting the mental health domain. Conclusion. QoL monitoring during antihypertensive therapy could not only improve therapy compliance, but also increase the motivation towards long-term treatment.

Observations from four periods (three late springs and one early summer) at temperate forest sites in western and eastern Canada offer the first estimation of how the concentrations of submicron forest organic aerosol mass (SFOM) from the oxidation of biogenic volatile organic compounds (BVOC) vary over the ambient temperature range of 7 °C to 34 °C. For the measurement conditions of clear skies, low oxides of nitrogen and within approximately one day of emissions, 50 estimates of SFOM concentrations show the concentrations increase exponentially with temperature. The model that is commonly used to define terpene emissions as a function of temperature is able to constrain the range of the SFOM values across the temperature range. The agreement of the observations and model is improved through the application of an increased yield of SFOM as the organic mass concentration increases with temperature that is based on results from chamber studies. The large range of SFOM concentrations at higher temperatures leaves open a number of questions, including the relative contributions of changing yield and of isoprene, that may be addressed by more ambient observations at higher temperatures.

Ambient particles collected on teflon filters at the Peak of Whistler Mountain, British Columbia (2182 m a.s.l.) during spring and summer 2009 were measured by Fourier transform infrared (FTIR) spectroscopy for organic functional groups (OFG). The project mean and standard deviation of organic aerosol mass concentrations (OM) for all samples was 3.2±3.3 (μg m−3). Measurements of aerosol mass fragments, size, and number concentrations were used to separate fossil-fuel combustion and burning and non-burning forest sources of the measured organic aerosol. The OM was composed of the same anthropogenic and non-burning forest components observed at Whistler mid-valley in the spring of 2008; during the 2009 campaign, biomass burning aerosol was additionally observed from fire episodes occurring between June and September. On average, organic hydroxyl, alkane, carboxylic acid, ketone, and primary amine groups represented 31 %±11 %, 34 %±9 %, 23 %±6 %, 6 %±7 %, and 6 %±3 % of OM, respectively. Ketones in aerosols were associated with burning and non-burning forest origins, and represented up to 27 % of the OM. The organic aerosol fraction resided almost entirely in the submicron fraction without significant diurnal variations. OM/OC mass ratios ranged mostly between 2.0 and 2.2 and O/C atomic ratios between 0.57 and 0.76, indicating that the organic aerosol reaching the site was highly aged and possibly formed through secondary formation processes.

This 12-month, open-label, flexible-dose study with an extension period evaluated the tolerability and efficacy of armodafinil in patients with excessive sleepiness associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy.Armodafinil-naïve, adult patients with excessive sleepiness associated with treated OSA (n = 170), SWD (n = 108), or narcolepsy (n = 50) received armodafinil (100-250 mg) once daily (treated OSA or narcolepsy) or before night shifts (SWD). Patients with OSA were regular users of continuous positive airway pressure (CPAP) therapy. Efficacy measures included the Clinical Global Impression of Improvement (CGI-I) and the Epworth Sleepiness Scale (ESS).Across the diagnosis groups, the most commonly occurring adverse event was headache (14%-24%). Forty-three patients (13%) and 13 patients (4%) were withdrawn because of adverse events and insufficient efficacy, respectively. Armodafinil did not adversely affect CPAP therapy. At the final visit, 80% (95% CI: 74.1, 86.7) of patients with treated OSA and 84% (72.7, 94.8) of patients with narcolepsy were rated on the CGI-I as at least minimally improved with regard to overall clinical condition; 98% (95.2, 100.0) of patients with SWD were rated as improved with regard to sleepiness during night shifts, including the commute to and from work. Armodafinil improved ESS total scores in patients with treated OSA (mean [SD] [95% CI] change from baseline, -7.3 [5.6] [-8.39, -6.30]) and patients with narcolepsy (-4.7 [6.0] [-7.41, -1.93]).Armodafinil administered for 12 months or more was generally well tolerated and improved wakefulness in patients with excessive sleepiness associated with treated OSA, SWD, or narcolepsy. Armodafinil improved the overall clinical condition of patients with treated OSA or narcolepsy.

Jonathan RL Schwartz1,Thomas Roth2, Chris Drake21INTEGRIS Sleep Disorders Center and University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; 2Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI, USAAbstract: Excessive sleepiness (ES) is a major but underestimated public health concern associated with significant impairments in alertness/wakefulness and significant morbidity. The term ES has been used in the sleep medicine literature for years, but due to its nonspecific symptoms (ie tiredness or fatigue), it frequently goes unrecognized or is misdiagnosed in primary care. In some cases ES arises due to poor sleep habits or self-imposed sleep deprivation; however, ES is also a key component of a number of sleep/wake disorders and multiple medical and psychiatric disorders. Identification and treatment of ES is critical to improve the quality of life and well-being of patients and for the safety of the wider community. The inability of patients to recognize the nature, extent, and symptomatic profile of sleep/wake disorders requires vigilance on the part of healthcare professionals. Interventions to address ES and its associated impairments, treatment of the underlying sleep/wake disorder, and follow-up are a priority given the potential for serious consequences if left untreated. Wakefulness-promoting agents are available that treat ES associated with sleep/wake disorders. This review examines current approaches for managing this debilitating and potentially life-threatening condition, focusing on the place of armodafinil as a wakefulness-promoting agent.Keywords: excessive sleepiness, wakefulness, armodafinil, obstructive sleep apnea, narcolepsy, shift-work disorder

Submicron particles collected at Whistler, British Columbia, at 1020 m a.s.l. during May and June 2008 on Teflon filters were analyzed by Fourier transform infrared (FTIR) and X-ray fluorescence (XRF) techniques for organic functional groups (OFG) and elemental composition. Organic mass (OM) concentrations ranged from less than 0.5 to 3.1 μg m−3, with a project mean and standard deviation of 1.3±1.0 μg m−3 and 0.21±0.16 μg m−3 for OM and sulfate, respectively. On average, organic hydroxyl, alkane, and carboxylic acid groups represented 34%, 33%, and 23% of OM, respectively. Ketone, amine and organosulfate groups constituted 6%, 5%, and