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OBJECTIVE To investigate if the extent of absent end-diastolic flow (AEDF) on umbilical artery (UA) Doppler velocimetry predicts pregnancy outcome. METHODS This was a retrospective observational study based on data from 25 000 Doppler examinations of UA flow performed between 1998 and 2017 at the Blood Flow Laboratory, Level III Perinatal Center, Lund, Sweden. All pregnancies with AEDF in the UA were identified, and the duration of AEDF as a proportion of the total duration of the cardiac cycle (Ta /Ttot ratio) was measured in digital images of the Doppler spectrum recorded at the last examination showing AEDF before delivery. Clinical data on pregnancies and neonatal outcomes were extracted from the regional perinatal database and the hospital patient records. The predictive performance of the Ta /Ttot ratio for intrauterine death and any (intrauterine or postnatal) death was assessed. RESULTS A total of 170 fetuses (122 (72%) singletons and 48 (28%) twins) were included in the study. Median gestational age at birth was 189.5 days (range, 163-279 days) (i.e. 27 + 0 weeks (range, 23 + 2 to 39 + 6 weeks)), birth weight was 650 g (range, 320-3326 g) and deviation from expected birth weight (standard deviation score) was -2.975 (range, -6.38 to 0.69). There were 15 (9%) intrauterine and 26 (15%) postnatal deaths. The principal outcome variables and their relationship with Doppler velocimetry results did not differ significantly between singletons and twins, giving a rationale for using the Ta /Ttot ratio in the total study group. Mean Ta /Ttot ratio was 0.42 ± 0.08 and 0.34 ± 0.08 in stillborn and liveborn fetuses, respectively (P = 0.002). For fetuses examined before 30 weeks' gestation, a Ta /Ttot ratio cut-off of 0.30 predicted intrauterine death with 92% sensitivity and a negative predictive value (NPV) of 98% (area under receiver-operating-characteristics curve (AUC), 0.74) and predicted any death with 83% sensitivity and a NPV of 85% (AUC, 0.66). CONCLUSIONS In fetuses with AEDF in the UA, duration of absent flow for at least 30% of the total cardiac cycle length might predict the risk of fetal demise, even when assessed before 30 weeks' gestation. This finding is particularly relevant to growth-restricted fetuses. After evaluation in further studies, the extent of AEDF might facilitate obstetric decision-making in very preterm growth-restricted fetuses. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

Background In Japan, ivabradine is indicated in patients with heart failure (HF) with sinus rhythm and a resting heart rate (HR) ≥75/min under standard treatment. Particularly, it is effective for HF with reduced left ventricular ejection fraction (LVEF). However, elderly people have a higher incidence of atrial fibrillation than young people, and their sinus node function is further deteriorated, resulting in a lower intrinsic HR. In addition, Japan is an ultra-aging society, especially in the countryside; therefore, the target patients for ivabradine may be limited in these regions. Purpose We sought to estimate the possible candidates for ivabradine and investigate their clinical characteristics in our hospital located in rural Japan. Method and results We retrospectively studied 14733 consecutive patients who were suspected heart disease who underwent echocardiography between January 2006 and October 2018 in Kitaishikai Hospital located in Ozu city (Proportion of the population aged ≥65 years: 34%, in 2015) and did not take ivabradine treatment. Of these, 187 patients with hemodynamically stable condition whose E/A ratio was measured and met the criteria of LVEF Conclusion In rural Japan, possible candidates for ivabradine may be rare, so daily attention should be paid. Patients with reduced ejection fraction, small left ventricle, and hemodialysis may be the possible targets for this therapy. Funding Acknowledgement Type of funding sources: None.

Study question Can a scoring model based on morphokinetic data developed to predict pregnancy rates of day–5 blastocyst transfers (KIDSCORE™D5) predict pregnancy rates of day–6 blastocyst transfers? Summary answer KIDSCORE™D5 was able to predict the clinical pregnancy rates of embryo transfers done on day 6 with an area under the curve (AUC) of 0.72. What is known already KIDSCORE™D5 is a scoring model based on morphokinetic data developed to predict the pregnancy rates of day–5 blastocysts. In 2019, Regnier et al. reported that the AUC of KIDSCORE™D5 for predicting clinical pregnancy rates of day–5 blastocyst transfers was 0.6. However, as KIDSCORE™D5 is constructed based on morphological characteristics and developmental dynamics of day–5 blastocysts, it is unclear whether KIDSCORE™D5 can predict pregnancy rates of day–6 blastocyst transfers. Since there are many cases of day–6 blastocyst transfers, it is important to know if KIDSCORE™D5 can predict pregnancy rates of day–6 blastocyst transfers. Study design, size, duration This retrospective single-center study, which included 162 day–5 and 72 day–6 blastocyst transfers, respectively, was conducted at Takahashi Women’s clinic from January to December 2019. Blastocysts derived from 146 patients who underwent intracytoplasmic sperm injection. All blastocysts were cryopreserved and were transferred singly. Participants/materials, setting, methods We used EmbryoScope+™ (Vitrolife) for in-vitro culture and calculated KIDSCORE™D5 (ver.3) using Embryoviewer™ (Vitrolife). Blastocyst scoring was done from 1.0 to 9.9. Clinical pregnancy was defined as the presence of a gestational sac confirmed by transvaginal ultrasonography. Statistical analysis was performed with JMP Pro 15.00 (SAS). The relationship between KIDSCORE™D5 and clinical pregnancy was evaluated by the AUC using ROC curve analysis and multivariate analysis adjusted for patient age. Main results and the role of chance The mean KIDSCORE™D5 of day–5 and day–6 blastocysts was 7.1±1.7 and 3.7±1.5, respectively. KIDSCORE™D5 of day–6 blastocysts was significantly lower than that of day–5 blastocysts (p Limitations, reasons for caution This study had a small sample size, and it was a retrospective single-center study. In addition, the relationship between KIDSCORE™D5 and clinical pregnancy rates may vary among facilities. Therefore, a prospective multicenter validation is necessary. Wider implications of the findings: Our study results indicated that KIDSCORE™D5 predicted clinical pregnancy and that morphokinetic parameters related to clinical pregnancy were similar between day–5 and day–6 blastocysts. Hence, morphokinetic evaluation can serve as a criterion for deciding which of multiple day–6 blastocysts can be transferred. Trial registration number Not applicable

2020 is the year of wildfire records. California experienced its three largest fires early in its fire season. The Pantanal, the largest wetland on the planet, burned over 20% of its surface. More than 18 million hectares of forest and bushland burned during the 2019–2020 fire season in Australia, killing 33 people, destroying nearly 2500 homes, and endangering many endemic species. The direct cost of damages is being counted in dozens of billion dollars, but the indirect costs on water‐related ecosystem services and benefits could be equally expensive, with impacts lasting for decades. In Australia, the extreme precipitation (“200 mm day −1 in several location”) that interrupted the catastrophic wildfire season triggered a series of watershed effects from headwaters to areas downstream. The increased runoff and erosion from burned areas disrupted water supplies in several locations. These post‐fire watershed hazards via source water contamination, flash floods, and mudslides can represent substantial, systemic long‐term risks to drinking water production, aquatic life, and socio‐economic activity. Scenarios similar to the recent event in Australia are now predicted to unfold in the Western USA. This is a new reality that societies will have to live with as uncharted fire activity, water crises, and widespread human footprint collide all‐around of the world. Therefore, we advocate for a more proactive approach to wildfire‐watershed risk governance in an effort to advance and protect water security. We also argue that there is no easy solution to reducing this risk and that investments in both green (i.e., natural) and grey (i.e., built) infrastructure will be necessary. Further, we propose strategies to combine modern data analytics with existing tools for use by water and land managers worldwide to leverage several decades worth of data and knowledge on post‐fire hydrology., Wildfires are a source of socio‐hydrological extremes that increasingly threaten water security across the world; this situation may be referred to as wildfire‐watershed risks (WWR). WWR geographically vary and require locally‐adapted governance for efficient disaster risk reduction. A combination of watershed protection, forest restoration (including fire reintroduction), and adaptation of water infrastructures is the answer to reduce water supply vulnerability to wildfires.

Background Posttraumatic stress disorder (PTSD) is a frequent problem of veterans receiving care and is often associated with cognitive deficits. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a well-validated cognitive screening measure often used in the US Department of Veterans Affairs (VA), particularly in neurorehabilitation settings. However, the influence of PTSD on RBANS performance is unclear, particularly within a heterogeneous VA outpatient population in which PTSD and traumatic brain injury (TBI) may not be the primary focus of care. Methods Participants included 153 veterans with complex deployment-related health problems, including a diagnosis of PTSD (n = 98) and a history of TBI (n = 92). All veterans completed a targeted cognitive battery that included the Wechsler Test of Adult Reading, the Wechsler Adults Intelligence Scale, measure assessing processing speed, attention, and cognitive flexibility, and RBANS. Results A diagnosis of PTSD was associated with worse performance on the Story Recall subtest of the RBANS, but not on any other cognitive measures. A diagnosis of mild TBI, or co-occurring PTSD and TBI did not predict cognitive performance on any measures. Conclusions The RBANS best captured cognitive deficits associated with PTSD compared with a history of mild TBI or co-occurring mild TBI and PTSD. These findings may provide insight into the interpretation and attribution of cognitive deficits in the veteran population.

Background Biodegradable polymer drug-eluting stents (BP-DES) has been developed to overcome the potential drawbacks of the first-generation durable polymer drug-eluting stents (DP-DES). However, it is still under debate whether BP-DES is associated with superior efficacy and safety over DP-DES. Purpose We sought to compare the effects of BP-DES and DP-DES in patients with coronary artery disease. Methods We performed systematic review and a meta-analysis of randomized controlled trials comparing BP-DES and DP-DES on clinical outcomes in patients with coronary artery disease using CE-mark approved drug-eluting stents (DES) with at least 1-year follow-up. We included 32 studies involving 39,686 patients (BP-DES: 21,439 patients, and DP-DES: 18,247 patients). Primary outcome measure was target vessel failure (TVF; equivalent to the composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven target vessel revascularization). We performed subgroup analysis according to the DP-DES generations (newer-generation DP-DES: 15,179patients, and first-generation DP-DES: 3,068 patients), and the effects of newer-generation DP-DES was compared with the BP-DES according to the BP-DES strut thickness (Ultra-thin strut [ Results The odds for TVF was not significantly different between the BP-DES group and the DP-DES group in the entire study population (odds ratio [OR] 0.96, 95% confidence interval [CI] [0.90–1.02], P=0.20). The odds for TVF was significantly low in the BP-DES group relative to the first-generation DP-DES group, however the odds were comparable between the BP-DES group and the newer-generation DP-DES group (BP-DES versus first-generation DP-DES: OR 0.82, 95% CI [0.73–0.92], P Conclusions In this meta-analysis of randomized controlled trials evaluating clinical outcomes, there was no significant differences between BP-DES and DP-DES. We found beneficial effects of BP-DES relative to the first-generation DP-DES, however, there was no statistical differences between BP-DES and newer-generation DP-DES, irrespective of the BP-DES strut thickness. Pooled odds ratios for clinical outcomes Funding Acknowledgement Type of funding source: None

Post-fire hydrologic research typically focuses on the first few years after a wildfire, leading to substantial uncertainty regarding the longevity of impacts. The time needed for hydrologic function to return to pre-fire conditions is critical information for post-fire land and water management decisions. This is particularly true in Mediterranean climates, where water is scarce and in high demand, and the severity and area burned by wildfires are increasing. In part, uncertainty about hydrologic recovery is due to lack of a consistent definition or interpretation of what constitutes “recovery.” Here, we systematically reviewed empirical studies from Mediterranean climates with at least three years of post-fire hydrologic data with the objectives of (a) assessing the recovery period, (b) identifying a definition of post-fire hydrologic recovery, (c) demonstrating a simple analytical approach to aid in assessment of recovery, and (d) outlining research needs and opportunities to better quantify post-fire recovery. We assessed the hydrologic effects reported in 38 sites that were monitored for 3–20 years. Eighteen sites were considered recovered within seven years; however, the recovery time was inconsistent across sites and was not related to location, response variable, or study design. The likelihood of recovery within the study period also decreased with increasing proportion of the watershed area burned. Importantly, we have also proposed a standardized definition and an approach to quantifying hydrologic recovery that may facilitate cross-study comparisons and a deeper understanding of recovery. Specifically, we propose hydrologic recovery has occurred when a specific post-fire hydrologic function or condition of interest returns to the 95% confidence interval of the pre-fire condition. In support of this definition, we have demonstrated applying this simple approach to assess recovery and presented future research topics to improve our understanding of long-term post-fire catchment responses. In addition to the need for more studies that quantify hydrologic responses farther into the post-fire period, understanding post-fire changes in soil structural and hydraulic properties through time will improve our mechanistic understanding of post-fire hydrologic responses and recovery.

Fluorescence spectroscopy has been increasingly used to detect sewage and other anthropogenic contaminants in surface waters. Despite progress in successfully detecting bacterial and sewage inputs to rivers over diverse spatial scales, the use of fluorescence-based in-situ sensors to track contaminant inputs during storm events and to discern bacterial contamination from background natural organic matter (NOM) fluorescence have received less attention. A portable, submersible fluorometer equipped with tryptophan (TRP)-like and humic-like fluorescence sensors was used to track inputs of untreated wastewater added to natural creek water in a laboratory sewage spill simulation. Significant, positive correlations were observed between TRP fluorescence, the TRP:humic ratio, percent wastewater, and Escherichia coli concentrations, indicating that both the TRP sensor and the TRP:humic ratio tracked wastewater inputs against the background creek water DOM fluorescence. The portable fluorometer was subsequently deployed in an urban creek during a storm in 2018. The peak in TRP fluorescence was found to increase with the rising limb of the hydrograph and followed similar temporal dynamics to that of caffeine and fecal indicator bacteria, which are chemical and biological markers of potential fecal pollution. Results from this study demonstrate that tracking of TRP fluorescence intensity and TRP:humic ratios, with turbidity correction of sensor outputs, may be an appropriate warning tool for rapid monitoring of sewage or other bacterial inputs to aquatic environments.

Objective Obstructive Sleep Apnea (OSA) is associated with neuropsychological challenges, including attentional difficulties (Kim et al., 2017), and commonly comorbid with Posttraumatic Stress Disorder (PTSD) in veteran samples (Yesavage et al., 2014). We further explore the relationship between OSA and cognition in veterans with PTSD symptomatology. Method 58 veterans (6 females; mean age = 57.53 years, SD = 13.63) with OSA were screened as part of a larger outpatient study at Palo Alto VA Hospital, completing neuropsychological testing and Clinician Administered PTSD Scale for DSM-5 (CAPS-5) interview. Mean Apnea Hypopnea Index (AHI) was 23.95 (SD = 15.97). Positive Airway Pressure (PAP) therapy had not started at the time of screening. Domain-specific composite scores were created using z-score transformation of individual test scores and hierarchical regression used. Results Initial regression model was significant (F(1,57) = 4.99, p = 0.03, R2 = 0.081) with AHI significantly predicting executive function (EF; β = −0.28, p = 0.03). Attention was then entered into the model (F(2,56) = 22.31, p Conclusions Findings suggest that EF concerns related to OSA may be driven by decreased attention performance, suggesting areas to highlight when formulating recommendations and treatment planning. Further implications and directions to be discussed. Funding Acknowledgements Supported by the Research Service of the Department of Veterans Affairs (Grant Number 1I01RX001799-01A2), VAPAHCS, and Sierra-Pacific MIRECC.

Light Detection and Ranging (LiDAR) methods, such as ground-based Terrestrial Laser Scanning (TLS), have enabled collection of high-resolution point clouds of elevation data to calculate changes in fluvial systems after disturbance, but are often accompanied by uncertainty and errors. This paper reviews and compares TLS analysis methods and develops a workflow to estimate topographic and volumetric changes in channel sedimentation after disturbance. Four analytic methods to estimate topographic and volumetric changes were compared by quantifying the uncertainty in TLS-derived products: Digital Elevation Model (DEM) of difference (DOD), Cloud to Cloud (C2C), Cloud to Mesh (C2M), and Multiple Model to Model Cloud Comparison (M3C2). Mean errors across surfaces within each dataset contributed to a propagation error of 0.015–0.016 m and 0.017–0.018 m for the point clouds and derived DEMs, respectively. The estimated error of the total volumetric change implied increased errors in the conversion of point clouds into a surface by C2M and DOD; whereas C2C and M3C2 were generally simpler, efficient, and accurate techniques for evaluating topographic changes. The comparison of methods to analyze TLS data will contribute to applications of remote sensing of hydro-geomorphic processes in stream channels after disturbance. The workflow presented also aids in estimating uncertainties inherent in data collection and analytic methods for topographic and volumetric change analysis.

Background:Dendritic cells (DCs) play important roles in inducing immune response as well as maintaining immune tolerance. Src homology 2 domain-containing protein tyrosine phosphatase-1 (Shp1) is a negative regulator of signaling in hematopoietic cells and is expressed in a variety of immune cells including DCs. Shp1 homozygous mutant mice (motheaten mice) develop multiple immunological abnormalities and they die around four weeks after birth because of severe pneumonitis. Motheaten mice produce large amounts of autoantibodies, and besides, B-1a cells, a distinct B cell subset, which are an important source of autoantibodies increase in these mice. The functional abnormality of DCs in motheaten mice has not been characterized, but DCs and macrophages increase in various organs of motheaten mice.To analyze the function of Shp1 in DCs, we generated Shp1 conditional knockout mice (Shp1 CKO) in whichShp1gene is specifically depleted in CD11c+cells. We found that aged shp1 CKO developed autoimmune glomerulonephritis. We also found that they developed severe tubulointerstitial nephritis (TIN) at the age of 40 weeks, which is characterized by the infiltration of CD11c+and F4/80+cells. CD4+T cells from Shp1 CKO produce much more amount of IFNγ. Collectively, Shp1 in DCs acts as a key regulatory molecule to protect against autoimmunity.Objectives:We analyzed salivary glands of CKO to confirm whether they have autoimmune sialadenitis because TIN is known to be the most common renal manifestations of Sjögren’s syndrome in human.Methods:Shp1 CKO are generated by crossing a mouse line carrying floxedShp1allele to mice expressing Cre recombinase under the control of the CD11c promoter. Sex- and age-matchedPtpn6fl/fllittermates withoutCregene were studied as controls. We analyzed secretory function of the salivary glands in response to pilocarpine stimulation in Shp1 CKO at the age of 40 weeks or older. We then performed histological examination of salivary glands (submandibular glands and sublingual glands) with light-microscopy and immunohistochemical staining. The mononuclear cells prepared from the salivary glands were analyzed by flow cytometry (FCM). We also quantified anti-SSA/Ro60 antibodies and anti-SSB/LA antibodies by ELISA.Results:Shp1 CKO secreted less saliva flow compared to control mice by pilocarpine stimulation. Histological study showed Shp1 CKO exhibited massive infiltration of inflammatory cells in salivary glands associated with periductal foci and periductal fibrosis. Most of infiltrated cells were stained by anti- CD4 or B220 mAbs. FCM revealed that B cells increased in the salivary glands of Shp1 CKO. In addition, B-1a cells also increased in the salivary glands of the mice. The levels of anti-SSA/Ro60 antibodies and anti-SSB/LA antibodies were increased in Shp1 CKO.Conclusion:CD11c-specific ablation of Shp1 induces the ectopic generation of lymphoid structure in salivary glands and impairment of salivary secretion. Autoantibody profile in Shp1 CKO resembled that in human Sjögren’s syndrome. Our findings suggest that aged Shp1 CKO have the potential to become a new mouse model for the analysis of Sjögren’s syndrome.References:[1]Green C. M. et al. J Heredity. 1975; 250-258.[2]Kaneko T. et al. J Immunology. 2012; 5397-540.[3]Watanabe M. et al. Biochem Biophys Rep. in press.Disclosure of Interests:Masato Kinoshita: None declared, Yoriaki Kaneko Grant/research support from: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc.b, Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Mitsuharu Watanabe: None declared, Yoichi Imai: None declared, Shreya Shrestha: None declared, Junya Suwa: None declared, Yuko Ohishi: None declared, Hiroko Hamatani: None declared, Masao Nakasatomi: None declared, Toru Sakairi: None declared, Hidekazu Ikeuchi Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Yoshihisa Nojima: None declared, Keiju Hiromura Grant/research support from: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc.

Single-cell omics provide insight into cellular heterogeneity and function. Recent technological advances have accelerated single-cell analyses, but workflows remain expensive and complex. We present a method enabling simultaneous, ultra-high throughput single-cell barcoding of millions of cells for targeted analysis of proteins and RNAs. Quantum barcoding (QBC) avoids isolation of single cells by building cell-specific oligo barcodes dynamically within each cell. With minimal instrumentation (four 96-well plates and a multichannel pipette), cell-specific codes are added to each tagged molecule within cells through sequential rounds of classical split-pool synthesis. Here we show the utility of this technology in mouse and human model systems for as many as 50 antibodies to targeted proteins and, separately,70 targeted RNA regions. We demonstrate that this method can be applied to multi-modal protein and RNA analyses. It can be scaled by expansion of the split-pool process and effectively renders sequencing instruments as versatile multi-parameter flow cytometers.

Introduction The occurrence of obstructive sleep apnea (OSA) is high in veterans with posttraumatic stress disorder (PTSD). Our previous research on OSA in Vietnam-era veterans found that 69% had an AHI≥10 (Yesavage, 2012). Efficacious treatments are available for OSA, PAP therapy; however, veterans with OSA frequently fail to use them (Yesavage, 2012; Kuna, 2011). Of the veterans diagnosed with OSA, 63% were not using their prescribed PAP device. The reasons for low PAP adherence include discomfort using PAP and psychological barriers. We developed a novel cognitive-behavioral therapy (CBT) intervention to increase PAP adherence in veterans with PTSD and OSA, called CBT-OSA. Methods Participants included 37 veterans age 18+ from clinics at VA Palo Alto. Participants were randomly assigned to CBT-OSA or an education arm. All participants received treatment as usual in VA Pulmonary Service or a community-based Sleep Medicine Center. Participants in CBT-OSA received therapy from a Clinical Psychologist. The other veterans received education sessions. All participants received weekly, individual sessions during the first four weeks of PAP treatment. Average mask on time was calculated for each participant during week 1-4 of PAP use. Results An independent samples t-test was conducted to compare average mask on time in the CBT-OSA and education conditions. There was a significant difference in the average mask on time for CBT-OSA (M=235.33, SD=139.22) and education (M=136.68; SD=149.19); t(35)=-2.08, p=0.045. These results suggest that veterans who received the CBT treatment increased their PAP use compared to the veterans in the education condition. Conclusion CBT-OSA has shown early efficacy. CBT-OSA increased PAP adherence in veterans with PTSD compared to veterans in the education condition. Veterans receiving CBT-OSA demonstrated a longer average mask on time compared to veterans in the education condition. We are following the participants for one year to examine if CBT-OSA fosters long-term PAP adherence. Support This research is supported by the Research Service of the Department of Veterans Affairs (Grant Number 1I01RX001799-01A2).

In the hydrological cycle, evapotranspiration (ET) transfers moisture from the land surface to the atmosphere and is sensitive to disturbances such as wildfires. Ground-based pre- and post-fire measurements of ET are often unavailable, limiting the potential to understand the extent of wildfire impacts on the hydrological cycle. This research estimated both pre- and post-fire ET using remotely sensed variables and support vector machine (SVM) methods. Input variables (land surface temperature, modified soil-adjusted vegetation index, normalized difference moisture index, normalized burn ratio, precipitation, potential evapotranspiration, albedo and vegetation types) were used to train and develop 56 combinations that yielded 33 unique SVM models to predict actual ET. The models were trained to predict a spatial ET, the Operational Simplified Surface Energy Balance (SSEBop), for the 2003 Coyote Fire in San Diego, California (USA). The optimal SVM model, SVM-ET6, required six input variables and predicted ET for fifteen years with a root-mean-square error (RMSE) of 8.43 mm/month and a R2 of 0.89. The developed model was transferred and applied to the 2003 Old Fire in San Bernardino, California (USA), where a watershed balance approach was used to validate SVM-ET6 predictions. The annual water balance for ten out of fifteen years was within ±20% of the predicted values. This work demonstrated machine learning as a viable method to create a remotely-sensed estimate with wide applicability for regions with sparse data observations and information. This innovative work demonstrated the potential benefit for land and forest managers to understand and analyze the hydrological cycle of watersheds that experience acute disturbances based on this developed predictive ET model.

Objective Squamous cell carcinoma (SCC) is a rare histological type of breast cancer. The cytological diagnosis of non-keratinising, poorly differentiated SCC is often difficult, and distinguishing it from invasive ductal carcinoma or apocrine carcinoma (AC) is especially challenging. We aimed to define the diagnostic cytological features of poorly differentiated SCC of the breast. Methods We studied the cytological findings of poorly differentiated SCC (n=10) and compared them to those of IDC (n=15) and AC (n=14). The following six cytological features were evaluated: streaming arrangement, nucleolar enlargement, dense nuclei, cannibalism, atypical keratinocytes and necrotic background. Results SCC exhibited significantly higher frequencies of streaming arrangement (70% vs 6.7%, P=.002), nucleolar enlargement (80% vs 27%, P=.02), and necrotic background (80% vs 36%, P=.002) than invasive ductal carcinoma. The detection of two or three of these features yielded a higher sensitivity (80%) and specificity (93%) for the diagnosis of SCC. Streaming arrangement (70% vs 0%, P

We describe a cost-effective and low-power-consumption approach for on-chip optical interconnection. This approach includes an investigation into architectures, devices, and materials. We have proposed and fabricated a bonded structure of an Si-based optical layer on a large-scale integration (LSI) chip. The fabricated optical layer contains Si nanophotodiodes for optical detectors, which are coupled with SiON waveguides using surface-plasmon antennas. Optical signals were introduced to the optical layer and distributed to the Si nanophotodiodes. The output signals from the photodiodes were sent electrically to the transimpedance-amplifier circuitries in the LSI. The signals from the photodiodes triggered of the circuitries at 5 GHz. Since electrooptical modulators consume the most power in on-chip optical interconnect systems and require a large footprint, they are critical to establish on-chip optical interconnection. Two approaches are investigated: 1) an architecture using a fewer number of modulators and 2) high electrooptical coefficient materials.

A resistive-switching solid-state brain-neocortex-like device for advanced non-volatile logic applications was developed. This device can be used as a reconfigurable logic device that is operated by electrically connecting and disconnecting pairs of electrodes. This paper reports for the first time the experimental evaluation results of a three-terminal test element group as the unit for a solid state brain neocortex-like device. The solid-state brain-neocortex-like device was experimentally evaluated as unit in a three-terminal test element group. The evaluation results show that the neocortex-like reconfigurable switching, in particular, fringe-electric-field-induced switching is possible in the device.

Behçet’s disease is a chronic, relapsing, inflammatory disorder. This case report describes how use of an improvised topical negative pressure (TNP) device in a patient with a non-healing para-ileostomal ulcer with Behçet’s disease

A satellite-based potential evapotranspiration (PET) product for streamflow simulations is tested for 15 forecast basins in the Upper Mississippi and Red River watersheds under the forecasting responsibility of the National Weather Service (NWS) North Central River Forecast Center (NCRFC). PET demand curves, which are long-term average estimates of daily PET, are derived using the National Aeronautics and Space Administration’s moderate resolution imaging spectroradiometer sensor (MODIS) on board the Terra and Aqua earth observation satellites. The PET demand curves (referred to as M-PET) are then used as input to the NWS Sacramento soil moisture accounting model (SACSMA) and simulated discharge and evapotranspiration (ET) are evaluated. Simulations using M-PET input are compared to simulations produced using the demand curves of the NCRFC (referred to as NC-PET). The M-PET data correlate better with PET estimated using tower data from three sites located within the study region compared to the NC...

AlGaN/GaN HFETs were fabricated around micropipes and on a domain boundary in a semi-insulating silicon carbide (SI-SiC) substrate and the DC characteristics of the fabricated devices were measured. Devices around micropipe showed no pinch-off or large gate leakage. The devices on the domain boundaries showed no degradation in the performances, even though an X-ray topographic analysis indicated that crystal imperfections, due to the defects, propagated to the GaN layer across the hetero interface. Based on these results, we concluded that micropipe degrades the DC characteristics and that the domain boundary does not affect the DC characteristics. From Raman analysis on the devices around the micropipes, these degradations could be attributed to the free carriers introduced into the GaN crystal by the micropipes.

Veterans who have been deployed to combat often have complex medical histories including some combination of traumatic brain injury (TBI); mental health problems; and other chronic, medically unexplained symptoms (i.e., chronic multisymptom illness [CMI] clusters). How these multiple pathologies relate to functional health is unclear. In the current study, 120 Veterans (across multiple combat cohorts) underwent comprehensive clinical evaluations and completed self-report assessments of mental health symptoms (Patient Health Questionnaire-2 [PHQ-2], PTSD Checklist-Civilian Version [PCL-C]) and functional health (Veterans Rand 36-Item Health Survey). Canonical correlation and regression modeling using split-sample permutation tests revealed that the PHQ-2/PCL-C composite variable (among TBI severity and number of problematic CMI clusters) was the primary predictor of multiple functional health domains. Two subscales, Bodily Pain and General Health, were associated with multiple predictors (TBI, PHQ-2/PCL-C, and CMI; and PHQ-2/PCL-C and CMI, respectively), demonstrating the multifaceted nature of how distinct medical problems might uniquely and collectively impair aspects of functional health. Apart from these findings, however, TBI and CMI were not predictors of any other aspects of functional health. Taken together, our findings suggest that mental health problems might exert ubiquitous influence over multiple domains of functional health. Thus, screening of mental health problems and education and promotion of mental health resources can be important to the treatment and care of Veterans.

Objective To determine the point prevalence of sleep disordered breathing (SDB) in a community-based sample of older male veterans and to determine if common markers of SDB apply to this population. Methods Two hundred fourteen older male Veterans (age 55–89 years) were recruited for a study on post-traumatic stress disorder and cognitive decline. Questionnaires concerning anthropomorphic and psychological variables were obtained, as was an overnight polysomnographic examination of sleep. Results Only 13% of the participants lacked clinically meaningful SDB, whereas 33% had moderate SDB and 54% had severe SDB. Being overweight, self-reported snoring, and excessive daytime sleepiness all had good sensitivity (0.86–0.92) but very poor specificity (0.10–0.28) for the prediction of SDB. Conclusions Undiagnosed SDB was more than threefold higher than expected in these community-dwelling older veterans. Traditional markers of SDB were not specific for predicting clinically relevant SDB.

A 50nm topological-switching random-access memory (TRAM) was fabricated for the first time. A high-quality Ge x Te 1−x /Sb 2 Te 3 superlattice film enabled set and reset voltages of TRAM to be less than 40% of those of PRAM. Statistical analysis of 16kb data showed the reset voltage to be less than 1.2 V, the lowest as a TRAM test chip.

A 10-/spl mu/m-thick GaAs/AlGaAs vertical-cavity surface-emitting laser (VCSEL) was fabricated by lifting off GaAs/AlGaAs epitaxial layers from the GaAs substrate to achieve high-density optoelectronic (OE) integration. It was found that the thin-film VCSEL array with a length of 0.25 to 3.0 mm warped due to internal stress in the film itself. The shift created by warping reached 100 /spl mu/m, and this warping was analyzed with a curved cantilever model with a uniform internal stress of 10/sup 7/ to 10/sup 9/ N/m/sup 2/. To fabricate a thin-film VCSEL array simultaneously on a mount, a diced chip with a thickness of 130 /spl mu/m was solder bonded onto a glass mount first, followed by lifting off epitaxial layers containing GaAs/AlGaAs VCSELs from the GaAs substrate. Current-voltage-light output characteristics as well as light-emission spectra for thin-film VCSELs were measured and compared at temperatures between 25/spl deg/C and 75/spl deg/C. It was found that the dependence of the device characteristics of thin-film VCSELs on temperature was similar to that of VCSELs with a GaAs substrate. The light output of thin-film VCSELs was measured for 1000 h during continuous operation at 25/spl deg/C and 50/spl deg/C. About a 20% decrease in optical output in devices without resin mold and no degradation in devices buried in resin mold were observed. Device degradation might be attributable to the internal stress of 10/sup 7/ N/m/sup 2/ and film warp of 0.5-1.0 /spl mu/m. The thin-film devices buried in resin mold had no changes in laser threshold current before or after 1000 h of continuous operation.

This paper describes the fabrication of novel surface-mountable waveguide connectors and presents test results for them. To ensure more highly integrated and low-cost fabrication, we propose new three-dimensional (3-D) waveguide arrays that feature two-dimensionally integrated optical inputs/outputs and optical path redirection. A wafer-level stack and lamination process was used to fabricate the waveguide arrays. Vertical-cavity surface-emitting lasers (VCSELs) and photodiodes were directly mounted on the arrays and combined with mechanical transferable ferrule using active alignment. With the help of a flip-chip bonder, the waveguide connectors were mounted on a printed circuit board by solder bumps. Using mechanical transferable connectors, which can easily plug into the waveguide connectors, we obtained multi-gigabits-per-second transmission performance.

A 3.9-/spl mu/m pixel pitch VGA format 10-b digital output CMOS image sensor with 1.5 transistor/pixel has been developed for mobile applications. The newly developed CMOS pixel architecture realizes the minimum number of the transistors in one pixel. Small pixel size and sufficient fill factor are achieved by using the shared pixel architecture and floating diffusion driving. High conversion gain, low random noise, and low dark current are achieved by buried photodiode with complete charge transfer capability and correlated double sampling (CDS) circuit. The image sensor is fabricated in a thin planarized 0.35-/spl mu/m single poly-Si double-metal customized CMOS process in order to provide good image performance. The image sensor achieves low noise floor of 330 /spl mu/V and low dark current of 50 pA/cm/sup 2/ at 45/spl deg/C. This image sensor also realized various functions by on-chip digital and analog circuits.

As the population of the United States continues to live longer than in previous years, a larger number of older adults are being diagnosed with dementia or other memory-related conditions. The individuals who experience a tremendous amount of stress and burden are the caregivers for the individual with dementia. The majority of the dementia caregiver research has been conducted on Caucasian caregivers, and to a lesser extent on Latino and African American caregivers. However, there is a paucity of research based on Japanese American care-givers. An understanding of how Japanese culture often affects Japanese American caregivers will assist clinicians in providing culturally competent health care to this group of caregivers. The authors provide an overview of the Japanese caregiver literature, followed by a discussion of traditional Japanese cultural values as they apply to a case example that illustrates the interaction of Japanese cultural values and dementia care-giving.

This paper describes a 4-Mb embedded DRAM macro using novel fast random cycle architecture with sense-synchronized read/write (SSR/SSW). The test chip has been fabricated with a 0.15-/spl mu/m logic-based embedded DRAM process and the 1.5-V 143-MHz no-wait row random access operation has been confirmed. Data retention power is suppressed to 92 /spl mu/W owing to the hierarchical power supply and SSR. The macro size is 4.59 mm/sup 2/. The cell occupation ratio of the macro is 46%, which is the same as that of a conventional embedded DRAM macro. The macro size and the data retention power are 30% and 4.6%, respectively, of a 4-Mb embedded SRAM macro fabricated by an identical process.

A novel optoelectronic input/output interface module termed "active interposer" and polymeric waveguide film lamination technologies have been developed for optical interconnects between large-scale integration chips. The fabricated active interposers comprise vertical cavity surface emitting lasers, metal-semiconductor-metal photodiodes, submount, and Si circuits stacked via through-hole electrodes built inside the optoelectronic devices and submounted to achieve high-speed low-crosstalk noise and high-density interconnect performances. Also, waveguide film lamination technologies developed are capable of cost reductions. This paper describes the prototype demonstration of the active interposers assembled on the waveguide film-laminated printed circuit boards. Processing and test results of the fabricated optoelectronic devices suitable for three-dimensional stacking are also addressed.

Introduction – We present herein clinical, histological and magnetic resonance imaging (MRI) findings in a patient with Fukuyama-type congenital muscular dystrophy (FCMD). He is the first case report in the Japanese population living in Brazil. Case report – The child presented with neonatal hypotonia, delayed motor abilities and speech, seizures, cerebral and cerebellar gyrus abnormalities with signal intensity change in the white matter by MRI, high serum level of creatinephosphokinase (CK), and dystrophic skeletal muscle with normal merosin, α-sarcoglycan and dystrophin expression. The fukutin gene study showed one founder 3-kb retrotransposal insertion in the 3′-non-coding region, and in the other allele no mutation was detected after screening all exons and flanking introns by sequencing. Discussion – This case report emphasizes the importance to consider FCMD in Japanese people living in other countries.

Ge x Te 1−x /Sb 2 Te 3 superlattice topological-switching random access memory (TRAM) was developed. Set and reset currents of 55 µA, the lowest for an ULSI-grade device, were obtained. TEM analyses of the Ge-Te structures and novel superlattice fabrication enabled us to reveal the retention, endurance, and electrical characteristics of TRAM for the first time.

Jerome A Yesavage,1,2 Lisa M Kinoshita,1,2 Art Noda,2 Laura C Lazzeroni,2 Jennifer Kaci Fairchild,1,2 Leah Friedman,1,2 Gundeep Sekhon,1,2 Stephanie Thompson,1,2 Jauhtai Cheng,1,2 Jamie M Zeitzer1,2 1Department of Veterans Affairs Health Care System, Palo Alto, CA, USA; 2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA Purpose: Previous work has demonstrated the relatively high prevalence of risk factors for cognitive impairment, such as sleep disordered breathing (SDB) and obesity, in Vietnam War era veterans with post-traumatic stress disorder (PTSD). No data are currently available on the longitudinal stability of SDB as a risk factor for cognitive decline in that population, which this study now reports. Methods: Sample consisted of 48 veterans of the Vietnam War with PTSD who completed longitudinal sleep assessments over a 3-year period. The primary outcome measure, the Apnea-Hypopnea Index (AHI) indicator, was determined during standard overnight polysomnography. Body mass index (BMI) was calculated using standard measurements. Measures of cognitive function tapped auditory verbal memory as measured by the Rey Auditory Verbal Learning Test and executive functioning as measured by the Color-Word Interference Test of the Delis–Kaplan Executive Function System battery. Statistical analyses included mixed effects modeling. Results: In this sample, AHI increased significantly by 2.19 points per year (β=2.19; P

The fabrication of topological-switching random-access memory (TRAM), a new type of phase change memory, was investigated. The deposition and etching process technologies of a GeTe/Sb 2 Te 3 superlattice memory cell were developed and micro test structures of TRAM were fabricated. Analysis of the fabricated structures revealed that the electrical properties of TRAM were different from those of conventional phase change memory and the reset voltage of TRAM, 0.6 V, was less than that of PRAM, 1 V. The non-melting behaviors of resistance change in TRAM were clarified via thermal-conductivity measurements and device simulation.