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The document discusses the genomic profiles and outcomes of de novo versus therapy-related core binding factor acute myeloid leukemia (CBF-AML). It highlights that therapy-related cases may have inferior outcomes due to factors like older age and treatment toxicity. The study reviewed patients to evaluate genetic profiles and outcomes, finding no significant differences in genetic profiles between de novo and therapy-related cases. The study emphasizes the importance of monitoring measurable residual disease and considering intensive therapy and stem cell transplantation based on molecular MRD results. [Extracted from the article]

Measurable residual disease (MRD) monitoring independently predicts long-term outcomes in patients with acute myeloid leukemia (AML). Of the various modalities available, multiparameter flow cytometry–based MRD analysis is widely used and relevant for patients without molecular targets. In the transplant (HCT) setting, the presence of MRD pre-HCT is associated with adverse outcomes. MRD-negative remission status pre-HCT was also associated with longer overall (OS) and progression-free survival and a lower risk of relapse. We hypothesize that the combination of disease risk and MRD at the time of first complete remission (CR1) could identify patients according to the benefit gained from HCT, especially for intermediate-risk patients. We performed a retrospective analysis comparing the outcomes of HCT versus non-HCT therapies based on MRD status in AML patients who achieved CR1. Time-dependent analysis was applied considering time-to-HCT as a time-dependent covariate and compared HCT versus non-HCT outcomes according to MRD status at CR1. Among 336 patients assessed at CR1, 35.1% were MRD positive (MRDpos) post-induction. MRDpos patients benefitted from HCT with improved OS and relapse-free survival (RFS), while no benefit was observed in MRDneg patients. In adverse-risk patients, HCT improved OS (HR for OS 0.55; p = 0.05). In intermediate-risk patients, HCT benefit was not significant for OS and RFS. Intermediate-risk MRDpos patients were found to have benefit from HCT with improved OS (HR 0.45, p = 0.04), RFS (HR 0.46, p = 0.02), and CIR (HR 0.41, p = 0.02). Our data underscore the benefit of HCT in adverse risk and MRDpos intermediate-risk AML patients. [ABSTRACT FROM AUTHOR]

Purpose: Gold standard chemotherapy dosage is based on body surface area (BSA); however many patients experience dose-limiting toxicities (DLT). We aimed to evaluate the effectiveness of BSA, two-dimensional (2D) and three-dimensional (3D) body composition (BC) measurements derived from Lumbar 3 vertebra (L3) computed tomography (CT) slices, in predicting DLT in colon cancer patients. Methods: 203 patients (60.87 ± 12.42 years; 97 males, 47.8%) receiving adjuvant chemotherapy (Oxaliplatin and/or 5-Fluorouracil) were retrospectively evaluated. An artificial intelligence segmentation model was used to extract 2D and 3D body composition measurements from each patients' single mid-L3 CT slice as well as multiple-L3 CT scans to produce a 3D BC report. DLT was defined as any incidence of dose reduction or discontinuation due to chemotherapy toxicities. A receiver operating characteristic (ROC) analysis was performed on BSA and individual body composition measurements to demonstrate their predictive performance. Results: A total of 120 (59.1%) patients experienced DLT. Age and BSA did not vary significantly between DLT and non-DLT group. Females were significantly more likely to experience DLT (p = 4.9 × 10–3). In all patients, the predictive effectiveness of 2D body composition measurements (females: AUC = 0.50–0.54; males: AUC = 0.50–0.61) was equivalent to that of BSA (females: AUC = 0.49; males: AUC = 0.58). The L3 3D skeletal muscle volume was the most predictive indicator of DLT (AUC of 0.66 in females and 0.64 in males). Conclusion: Compared to BSA and 2D body composition measurements, 3D L3 body composition measurements had greater potential to predict DLT in CRC patients receiving chemotherapy and this was sex dependent. [ABSTRACT FROM AUTHOR]

In July 2021 extreme rainfall across Western Europe caused severe flooding and substantial impacts, including over 200 fatalities and extensive infrastructure damage within Germany and the Benelux countries. After the event, a hydrological assessment and a probabilistic event attribution analysis of rainfall data were initiated and complemented by discussing the vulnerability and exposure context. The global mean surface temperature (GMST) served as a covariate in a generalised extreme value distribution fitted to observational and model data, exploiting the dependence on GMST to estimate how anthropogenic climate change affects the likelihood and severity of extreme events. Rainfall accumulations in Ahr/Erft and the Belgian Meuse catchment vastly exceeded previous observed records. In regions of that limited size the robust estimation of return values and the detection and attribution of rainfall trends are challenging. However, for the larger Western European region it was found that, under current climate conditions, on average one rainfall event of this magnitude can be expected every 400 years at any given location. Consequently, within the entire region, events of similar magnitude are expected to occur more frequently than once in 400 years. Anthropogenic climate change has already increased the intensity of the maximum 1-day rainfall event in the summer season by 3–19 %. The likelihood of such an event to occur today compared to a 1.2 ∘ C cooler climate has increased by a factor of 1.2–9. Models indicate that intensity and frequency of such events will further increase with future global warming. While attribution of small-scale events remains challenging, this study shows that there is a robust increase in the likelihood and severity of rainfall events such as the ones causing extreme impacts in July 2021 when considering a larger region. [ABSTRACT FROM AUTHOR]

We here inter-compare four different tracking algorithms by applying them onto the precipitation fields of an ensemble of convection-permitting regional climate models (cpRCMs) and on high-resolution observational datasets of precipitation. The domain covers the Alps and the northern Mediterranean and thus we here analyse heavy precipitation events, that are renowned for causing hydrological hazards. In this way, this study is both, an inter-comparison of tracking algorithms as well as an evaluation study of cpRCMs in the Lagrangian frame of reference. The tracker inter-comparison is performed by comparison of two case studies as well as of climatologies of cpRCMs and observations. We find that that all of the trackers produce qualitatively equal results concerning characteristic track properties. This means that, despite of quantitative differences, equivalent scientific conclusions would be drawn. This result suggests that all trackers investigated are reliable analysis tools of atmospheric research. With respect to the model ensemble evaluation, we find an encouraging performance of cpRCMs in comparison to radar-based observations. In particular prominent hotspots of heavy precipitation events are well-reproduced by the models. In general most characteristic properties of precipitation events have positive biases. Assuming the under-catchment of precipitation in observations in a domain of such complex orography, this result is to be expected. Only the mean area of tracks is underestimated, while their duration is overestimated. Mean precipitation rate is estimated well, while maximum precipitation rate is overestimated. Furthermore, geometrical and rain volume are overestimated. We find that models overestimate the occurrence of precipitation events over all mountain chains, whereas over plain terrain in summer precipitation events are seen underestimated. This suggests that, despite the convection-permitting resolution, thermally driven thunderstorms are either not triggered or their dynamics still under-resolved. Eventually we find that biases in the spatio-temporal properties of precipitation events appear reduced when evaluating cpRCMs against Doppler radar-based and rain gauge-adjusted observational datasets of comparable spatial resolution, strengthening their role in evaluation studies. [ABSTRACT FROM AUTHOR]

Purpose: To compare the incidence, aetiology, and patterns of maxillofacial fracture presentations during the various stages of the 2020 Melbourne COVID-19 lockdown restrictions to periods outside lockdown in 2019 and 2020. Methods: This is a retrospective study of 344 subjects. The patterns of facial trauma presentations to a tertiary hospital in metropolitan Melbourne during the 2020 COVID-19 restrictions were compared to periods with no restrictions over 22 months from March 2019 to December 2020. Results: The incidence of maxillofacial fractures decreased by 28% during lockdown (0.41 vs. 0.57 injuries/day, P = 0.0003). Falls overtook interpersonal violence as the leading cause of fractures (44% of lockdown presentations vs. 25.7% of presentations outside lockdown, P = 0.002), while sporting injuries dropped drastically (4% vs. 17.1%, P = 0.005). Lockdowns saw an increase in the proportion of female patients (40% vs. 26.8%, P = 0.03) and a fivefold increase in proportion of domestic violence-related fractures (6.7% vs. 1.1%, P = 0.006). Alcohol-related injuries decreased significantly (11% vs. 21%, P = 0.03). Conclusions: While restrictions reduced rates of interpersonal violence and alcohol-related maxillofacial trauma, there was a higher proportion of injuries to females, increased falls, and domestic violence-related injuries. [ABSTRACT FROM AUTHOR]

Given her uncontrolled gastric leak, the additional Roux-en-Y gastrojejunostomy, jejunojejunostomy and SIJGET procedure with feeding jejunostomy was applied (see Fig. Conclusion Conversion to a Roux-en-Y gastrojejunostomy with a SIJGET is a novel and viable option for severe sleeve gastrectomy leaks. Keywords: Laparoscopic sleeve gastrectomy; Gastric sleeve leak; SIJGET; Bariatric surgery complications EN Laparoscopic sleeve gastrectomy Gastric sleeve leak SIJGET Bariatric surgery complications 2816 2819 4 07/13/22 20220801 NES 220801 Key Points • Staple line leaks are among the most feared complications, and the management of this condition is constantly evolving. 1 Untransected Roux-en-Y gastrojejunostomy and SIJGET procedure Patient B A 45-year-old man with a BMI of 53.4 kg/m SP 2 sp underwent an elective laparoscopic revision sleeve gastrectomy post a limited sleeve gastrectomy 2 years earlier that produced minimal weight loss. [Extracted from the article]

High resolution regional climate models are needed to understand how climate change will impact extreme precipitation. Current state-of-the-art climate models are Convection Permitting Models (CPMs) at kilometre scale grid-spacing. CPMs are often used together with convective parameterised Regional Climate Models (RCMs) due to high computational costs of CPMs. This study compares the representation of extreme precipitation events between a 12 km resolution RCM and a 2.2 km resolution CPM. Precipitation events are tracked in both models, and extreme events, identified by peak intensity, are analysed in a Northern European case area. Extreme event tracks show large differences in both location and movement patterns between the CPM and RCM. This indicates that different event types are sampled in the two models, with differences extending to much larger scales. We visualise event-development using area-intensity evolution diagrams. This reveals that for the 100 most extreme events, the RCM data is likely dominated by physically implausible events, so called 'grid-point storms', with unrealistically high intensities. For the 1000 and 10,000 most extreme events, intensities are higher for CPM events, while areas are larger for RCM extreme events. Sampling extreme events by season shows that differences between RCM and CPM in intensity and area in the top 100 extreme events are largest in autumn and winter, while for the top 1000 and top 10,000 events differences are largest in summer. Overall this study indicates that extreme precipitation projections from traditional coarse resolution RCMs need to be used with caution, due to the possible influence of grid-point storms. [ABSTRACT FROM AUTHOR]

Here we present the first multi-model ensemble of regional climate simulations at kilometer-scale horizontal grid spacing over a decade long period. A total of 23 simulations run with a horizontal grid spacing of ∼ 3 km, driven by ERA-Interim reanalysis, and performed by 22 European research groups are analysed. Six different regional climate models (RCMs) are represented in the ensemble. The simulations are compared against available high-resolution precipitation observations and coarse resolution (∼ 12 km) RCMs with parameterized convection. The model simulations and observations are compared with respect to mean precipitation, precipitation intensity and frequency, and heavy precipitation on daily and hourly timescales in different seasons. The results show that kilometer-scale models produce a more realistic representation of precipitation than the coarse resolution RCMs. The most significant improvements are found for heavy precipitation and precipitation frequency on both daily and hourly time scales in the summer season. In general, kilometer-scale models tend to produce more intense precipitation and reduced wet-hour frequency compared to coarse resolution models. On average, the multi-model mean shows a reduction of bias from ∼ −40% at 12 km to ∼ −3% at 3 km for heavy hourly precipitation in summer. Furthermore, the uncertainty ranges i.e. the variability between the models for wet hour frequency is reduced by half with the use of kilometer-scale models. Although differences between the model simulations at the kilometer-scale and observations still exist, it is evident that these simulations are superior to the coarse-resolution RCM simulations in the representing precipitation in the present-day climate, and thus offer a promising way forward for investigations of climate and climate change at local to regional scales. [ABSTRACT FROM AUTHOR]

This paper presents the first multi-model ensemble of 10-year, "convection-permitting" kilometer-scale regional climate model (RCM) scenario simulations downscaled from selected CMIP5 GCM projections for historical and end of century time slices. The technique is to first downscale the CMIP5 GCM projections to an intermediate 12–15 km resolution grid using RCMs, and then use these fields to downscale further to the kilometer scale. The aim of the paper is to provide an overview of the representation of the precipitation characteristics and their projected changes over the greater Alpine domain within a Coordinated Regional Climate Downscaling Experiment Flagship Pilot Study and the European Climate Prediction system project, tasked with investigating convective processes at the kilometer scale. An ensemble of 12 simulations performed by different research groups around Europe is analyzed. The simulations are evaluated through comparison with high resolution observations while the complementary ensemble of 12 km resolution driving models is used as a benchmark to evaluate the added value of the convection-permitting ensemble. The results show that the kilometer-scale ensemble is able to improve the representation of fine scale details of mean daily, wet-day/hour frequency, wet-day/hour intensity and heavy precipitation on a seasonal scale, reducing uncertainty over some regions. It also improves the representation of the summer diurnal cycle, showing more realistic onset and peak of convection. The kilometer-scale ensemble refines and enhances the projected patterns of change from the coarser resolution simulations and even modifies the sign of the precipitation intensity change and heavy precipitation over some regions. The convection permitting simulations also show larger changes for all indices over the diurnal cycle, also suggesting a change in the duration of convection over some regions. A larger positive change of frequency of heavy to severe precipitation is found. The results are encouraging towards the use of convection-permitting model ensembles to produce robust assessments of the local impacts of future climate change. [ABSTRACT FROM AUTHOR]

For the first time, we analyze 2.2 km UK Met Office Unified Model convection-permitting model (CPM) projections for a pan-European domain. These new simulations represent a major increase in domain size, allowing us to examine the benefits of CPMs across a range of European climates. We find a change to the seasonality of extreme precipitation with warming. In particular, there is a relatively muted response for summer, which contrasts with much larger increases in autumn and winter. This flattens the hourly extreme precipitation seasonal cycle across Northern Europe which has a summer peak in the present climate. Over the Western Mediterranean, where autumn is the main extreme precipitation season, there is a regional increase in hourly extreme precipitation frequency, but local changes for lower precipitation thresholds are often insignificant. For mean precipitation, decreases are projected across Europe in summer, smaller decreases in autumn, and increases in winter; comparable changes are seen in the driving general circulation model (GCM) simulations. The winter mean increase is accompanied by a large decrease of winter mean snowfall. Comparing the driving GCM projections with the CPM ones, the CPMs show a robust enhanced intensification of precipitation extremes at the convection-permitting scale compared to coarser resolution climate model projections across various European regions for summer and autumn. [ABSTRACT FROM AUTHOR]

We investigate the effect of using convection-permitting models (CPMs) spanning a pan-European domain on the representation of precipitation distribution at a climatic scale. In particular we compare two 2.2 km models with two 12 km models run by ETH Zürich (ETH-12 km and ETH-2.2 km) and the Met-Office (UKMO-12 km and UKMO-2.2 km). The two CPMs yield qualitatively similar differences to the precipitation climatology compared to the 12 km models, despite using different dynamical cores and different parameterization packages. A quantitative analysis confirms that the CPMs give the largest differences compared to 12 km models in the hourly precipitation distribution in regions and seasons where convection is a key process: in summer across the whole of Europe and in autumn over the Mediterranean Sea and coasts. Mean precipitation is increased over high orography, with an increased amplitude of the diurnal cycle. We highlight that both CPMs show an increased number of moderate to intense short-lasting events and a decreased number of longer-lasting low-intensity events everywhere, correcting (and often over-correcting) biases in the 12 km models. The overall hourly distribution and the intensity of the most intense events is improved in Switzerland and to a lesser extent in the UK but deteriorates in Germany. The timing of the peak in the diurnal cycle of precipitation is improved. At the daily time-scale, differences in the precipitation distribution are less clear but the greater Alpine region stands out with the largest differences. Also, Mediterranean autumnal intense events are better represented at the daily time-scale in both 2.2 km models, due to improved representation of mesoscale processes. [ABSTRACT FROM AUTHOR]

We investigate the global distribution of hourly precipitation and its connections with the El Niño–Southern Oscillation (ENSO) using both satellite precipitation estimates and the global sub-daily rainfall gauge dataset. Despite limited moisture availability over continental surfaces, we find that the highest mean and extreme hourly precipitation intensity (HPI) values are mainly located over continents rather than over oceans, a feature that is not evident in daily or coarser resolution data. After decomposing the total precipitation into the product of the number of wet hours (NWH) and HPI, we find that ENSO modulates total precipitation mainly through the NWH, while its effects on HPI are more limited. The contrasting responses to ENSO in NWH and HPI is particularly apparent at the rising branches of the Pacific and Atlantic Walker Circulations, and is also notable over land-based gauges in Australia, Malaysia, the USA, Japan and Europe across the whole distribution of hourly precipitation (i.e. extreme, moderate and light precipitation). These results provide new insights into the global precipitation distribution and its response to ENSO forcing. [ABSTRACT FROM AUTHOR]

The UK Met Office has previously conducted convection-permitting climate simulations over the southern UK (Kendon et al. in Nat Clim Change 4:570-576, 2014). The southern UK simulations have been followed up by a new set of northern UK simulations using the same model configuration. Here we present the mean and extreme precipitation projections from these new simulations. Relative to the southern UK, the northern UK projections show a greater summertime increase of return levels and extreme precipitation intensity in both 1.5km convection-permitting and 12km convection-parameterised simulations, but this increase is against a backdrop of large decreases in summertime mean precipitation and precipitation frequency. Similar to the southern UK, projected change is model resolution dependent and the convection-permitting simulation projects a larger intensification. For winter, return level increases are somewhat lower than for the southern UK. Analysis of model biases highlight challenges in simulating the diurnal cycle over high terrain, sensitivity to domain size and driving-GCM biases, and quality issues of radar precipitation observations, which are relevant to the wider regional climate modelling community. [ABSTRACT FROM AUTHOR]

We live in a digital age where information can be found instantaneously via the Internet. Studies have shown that consumers search for much of their medical information on the Internet, particularly utilizing blogs and social media platforms. As the mental health field is riddled with misinformation and stigma, this offers a unique opportunity for psychiatrists and mental health professionals to reach a broad audience for mental health education and advocacy. In this review, we discuss the various methods and techniques for blogging and social media. We then review the current recommendations for ethics and professionalism as well as make recommendations to strengthen our guidance in this new and evolving field. [ABSTRACT FROM AUTHOR]

Purpose Of Review: Mental health practitioners should understand the features of current, publicly available apps; the features of novel, research apps; and issues behind the integration of mobile apps and digital health services into clinical workflows.Recent Findings: The review is based on a research literature and the authors' clinical and healthcare administration experiences. Articles searched-on telepsychiatry, telemental health, mobile mental health, informatics, cellular phone, ambulatory monitoring, telemetry, and algorithms-were restricted to 2016 and 2017. Technologies are used in a variety of clinical settings, including patients with varying mental illness severity, social supports, and technological literacy. Good practices for evaluating apps, understanding user needs, and training and educating users can increase success rates. Ethics and risk management should be considered. Mobile apps are versatile. Integrating apps into psychiatric treatment requires addressing both patient and clinical workflows, design and usability principles, accessibility, social concerns, and digital health literacy. [ABSTRACT FROM AUTHOR]

Purpose Of Review: Participatory medicine and the availability of commercial technologies have given patients more options to view and track their health information and to communicate with their providers. This shift in the clinical process may be of particular importance in mental healthcare where rapport plays a significant role in the therapeutic process.Recent Findings: In this review, we examined literature related to the impact of technology on the clinical workflow and patient-provider rapport in the mental health field between January 2014 and June 2017. Thirty three relevant articles, of 226 identified articles, were summarized. The use of technology clinically has evolved from making care more accessible and efficient to leveraging technology to improve care, communication, and patient-provider rapport. Evidence exists demonstrating that information and communication technologies may improve care by better connecting patients and providers and by improving patient-provider rapport, although further research is needed. [ABSTRACT FROM AUTHOR]

B Correction to: Climate Dynamics b https://doi.org/10.1007/s00382-022-06555-z In this article the affiliation of the author Steven Chan has been changed from "School of Engineering, University of Newcastle, Callaghan, Australia" to "School of Engineering, Newcastle University, Newcastle-upon-Tyne, UK" The original article has been corrected. The original article can be found online at https://doi.org/10.1007/s00382-022-06555-z. [Extracted from the article]

Mutant isocitrate dehydrogenase (IDH) 1 and 2 proteins alter the epigenetic landscape in acute myeloid leukemia (AML) cells through production of the oncometabolite (R)-2-hydroxyglutarate (2-HG). Here we performed a large-scale RNA interference (RNAi) screen to identify genes that are synthetic lethal to the IDH1R132H mutation in AML and identified the anti-apoptotic gene BCL-2. IDH1- and IDH2-mutant primary human AML cells were more sensitive than IDH1/2 wild-type cells to ABT-199, a highly specific BCL-2 inhibitor that is currently in clinical trials for hematologic malignancies, both ex vivo and in xenotransplant models. This sensitization effect was induced by (R)-2-HG-mediated inhibition of the activity of cytochrome c oxidase (COX) in the mitochondrial electron transport chain (ETC); suppression of COX activity lowered the mitochondrial threshold to trigger apoptosis upon BCL-2 inhibition. Our findings indicate that IDH1/2 mutation status may identify patients that are likely to respond to pharmacologic BCL-2 inhibition and form the rational basis for combining agents that disrupt ETC activity with ABT-199 in future clinical studies. [ABSTRACT FROM AUTHOR]

Gastric cancer patients with positive peritoneal cytology as the only marker of metastatic disease have poor prognoses. There is no universal consensus on the most appropriate treatment regimen for this particular patient group. We reviewed and analyzed published data to determine the optimal treatment regimen for patients with peritoneal cytology-positive gastric adenocarcinomas. Six electronic databases were explored [PubMed, Cochrane (Systematic Reviews and Controlled Trials), PROSPERO, DARE, and EMBASE]. The primary outcome was overall survival with secondary outcomes including patterns of recurrence and treatment-related morbidity. Six studies were included for data extraction. There was no significant heterogeneity between studies. The use of S1 monotherapy was associated with a significant survival benefit (HR 0.48; 95 % CI 0.32-0.70; p = 0.0002). Intraoperative intraperitoneal chemotherapy (IIPC) with adjuvant chemotherapy showed a trend toward improvement in overall survival (HR 0.70; 95 % CI 0.47-1.04; p = 0.08). A recent randomized controlled trial examining extensive intraperitoneal lavage (EIPL) with IIPC showed a significant improvement in overall survival (5-year overall survival, 43.8 % for EIPL-IPC group compared with 4.6 % for IPC group). However, these promising results need to be validated in larger prospective randomized trials. [ABSTRACT FROM AUTHOR]

The intensification of precipitation extremes with climate change is of key importance to society as a result of the large impact through flooding. Observations show that heavy rainfall is increasing on daily timescales in many regions, but how changes will manifest themselves on sub-daily timescales remains highly uncertain. Here we perform the first climate change experiments with a very high resolution (1.5 km grid spacing) model more typically used for weather forecasting, in this instance for a region of the UK. The model simulates realistic hourly rainfall characteristics, including extremes, unlike coarser resolution climate models, giving us confidence in its ability to project future changes at this timescale. We find the 1.5 km model shows increases in hourly rainfall intensities in winter, consistent with projections from a coarser 12 km resolution model and previous studies at the daily timescale. However, the 1.5 km model also shows a future intensification of short-duration rain in summer, with significantly more events exceeding the high thresholds indicative of serious flash flooding. We conclude that accurate representation of the local storm dynamics is an essential requirement for predicting changes to convective extremes; when included we find for the model here that summer downpours intensify with warming. [ABSTRACT FROM AUTHOR]

Aberrant changes in the epigenome are now recognized to be important in driving the development of multiple human cancers including acute myeloid leukemia. Recent advances in sequencing technologies have led to the identification of recurrent mutations in genes that regulate DNA methylation including DNA methyltransferase 3A (DNMT3A), ten-eleven translocation 2 (TET2), and isocitrate dehydrogenase 1 (IDH1) and IDH2. These mutations have been shown to promote self-renewal and block differentiation of hematopoietic stem/progenitor cells. Acquisition of these mutations in hematopoietic stem cells can lead to their clonal expansion resulting in a pre-leukemic stem cell (pre-LSC) population. Pre-LSCs retain the ability to differentiate into the full spectrum of mature daughter cells but can become fully transformed with the acquisition of additional driver mutations. Here, we review the effects of mutations in DNMT3A, TET2, and IDH1/2 on mouse and human hematopoiesis, the current understanding of their role in pre-LSCs, and therapeutic strategies to eliminate this population which may serve as a cellular reservoir for relapse. [ABSTRACT FROM AUTHOR]

Three different resolution (50, 12, and 1.5 km) regional climate model simulations are compared in terms of their ability to simulate moderate and high daily precipitation events over the southern United Kingdom. The convection-permitting 1.5-km simulation is carried out without convective parametrisation. As in previous studies, increasing resolution (especially from 50 to 12 km) is found to improve the representation of orographic precipitation. The 50-km simulation underestimates mean precipitation over the mountainous region of Wales, and event intensity tends to be too weak; this bias is reduced in both the 12- and 1.5-km simulations for both summer and winter. In south-east England lowlands where summer extremes are mostly convective, increasing resolution does not necessary lead to an improvement in the simulation. For the 12-km simulation, simulated daily extreme events are overly intense. Even though the average intensity of summer daily extremes is improved in the 1.5-km simulation, this simulation has a poorer mean bias with too many events exceeding high thresholds. Spatial density and clustering of summer extremes in south-east England are poorly simulated in both the 12- and 1.5-km simulations. In general, we have not found any clear evidence to show that the 1.5-km simulation is superior to the 12-km simulation, or vice versa at the daily level. [ABSTRACT FROM AUTHOR]

We present an analysis of the seasonal, subseasonal, and diurnal variability of rainfall from COAPS Land-Atmosphere Regional Reanalysis for the Southeast at 10-km resolution (CLARReS10). Most of our assessment focuses on the representation of summertime subseasonal and diurnal variability. Summer precipitation in the Southeast United States is a particularly challenging modeling problem because of the variety of regional-scale phenomena, such as sea breeze, thunderstorms and squall lines, which are not adequately resolved in coarse atmospheric reanalyses but contribute significantly to the hydrological budget over the region. We find that the dynamically downscaled reanalyses are in good agreement with station and gridded observations in terms of both the relative seasonal distribution and the diurnal structure of precipitation, although total precipitation amounts tend to be systematically overestimated. The diurnal cycle of summer precipitation in the downscaled reanalyses is in very good agreement with station observations and a clear improvement both over their 'parent' reanalyses and over newer-generation reanalyses. The seasonal cycle of precipitation is particularly well simulated in the Florida; this we attribute to the ability of the regional model to provide a more accurate representation of the spatial and temporal structure of finer-scale phenomena such as fronts and sea breezes. Over the northern portion of the domain summer precipitation in the downscaled reanalyses remains, as in the 'parent' reanalyses, overestimated. Given the degree of success that dynamical downscaling of reanalyses demonstrates in the simulation of the characteristics of regional precipitation, its favorable comparison to conventional newer-generation reanalyses and its cost-effectiveness, we conclude that for the Southeast United states such downscaling is a viable proxy for high-resolution conventional reanalysis. [ABSTRACT FROM AUTHOR]

This study assesses the regional-scale summer precipitation produced by the dynamical downscaling of analyzed large-scale fields. The main goal of this study is to investigate how much the regional model adds smaller scale precipitation information that the large-scale fields do not resolve. The modeling region for this study covers the southeastern United States (Florida, Georgia, Alabama, South Carolina, and North Carolina) where the summer climate is subtropical in nature, with a heavy influence of regional-scale convection. The coarse resolution (2.5° latitude/longitude) large-scale atmospheric variables from the National Center for Environmental Prediction (NCEP)/DOE reanalysis (R2) are downscaled using the NCEP/Environmental Climate Prediction Center regional spectral model (RSM) to produce precipitation at 20 km resolution for 16 summer seasons (1990-2005). The RSM produces realistic details in the regional summer precipitation at 20 km resolution. Compared to R2, the RSM-produced monthly precipitation shows better agreement with observations. There is a reduced wet bias and a more realistic spatial pattern of the precipitation climatology compared with the interpolated R2 values. The root mean square errors of the monthly R2 precipitation are reduced over 93% (1,697) of all the grid points in the five states (1,821). The temporal correlation also improves over 92% (1,675) of all grid points such that the domain-averaged correlation increases from 0.38 (R2) to 0.55 (RSM). The RSM accurately reproduces the first two observed eigenmodes, compared with the R2 product for which the second mode is not properly reproduced. The spatial patterns for wet versus dry summer years are also successfully simulated in RSM. For shorter time scales, the RSM resolves heavy rainfall events and their frequency better than R2. Correlation and categorical classification (above/near/below average) for the monthly frequency of heavy precipitation days is also significantly improved by the RSM. [ABSTRACT FROM AUTHOR]

In normal colonic epithelium, the receptor tyrosine kinase, EphB2 interacts with ephrinB1 ligand to maintain the integrity and architecture of the colonic crypt. Loss of EphB2 is seen in most colorectal cancers and correlates with poor prognosis. In this study, we investigated the effects of two levels of EphB2 expression on cell migration and invasion in a colon cancer cell line and on the growth of tumour xenografts. An EphB2-negative colon cancer cell line (LIM2405) was transfected with a full-length EphB2 cDNA in a vector designed to respond to the drug tetracycline. The effect of two levels of EphB2 expression on the ability of cells to migrate through a porous barrier in response to a chemo-attractant and to invade through artificial basement membranes was tested in vitro. Finally, the effects of two expression levels of EphB2 on tumour growth using an in vivo model of colonic tumour xenograft in a mouse model were assessed. Expression of moderate levels of EphB2 significantly reduced the migration of tumour cells compared to control ( p < 0.05, Kruskal–Wallis test). Expression of high levels of EphB2 further reduced migration of tumour cells ( p < 0.05, Kruskal–Wallis test). Similarly, expression of EphB2 markedly reduces the invasive ability of tumour cells. The in vivo model of tumour growth showed that tumours with the highest level of EphB2 expression had a reduced risk of reaching a 10-mm size (defined event) compared with the control group (Cox regression, hazard ratio (HR) = 0.052, 95% CI 0.005–0.550; p = 0.014). Tumours derived from EphB2 expressing cells had a significantly reduced number of mitotic figures ( p < 0.05) and an increased number of apoptotic cells ( p < 0.05) compared to tumours from control cells. Even a moderate level of EphB2 expression has effects on tumour cells which results in reduced migration and invasiveness and slows the growth of colonic tumour implants in an in vivo model. [ABSTRACT FROM AUTHOR]

Websites are now the basic requirement to an increasing number of communication and business strategies. The usability of a website, effectiveness of its interface, as well as its amount of information, ease of navigation, and user friendliness of its functions, are central to the success of these strategies. Yet these important design qualities remain to date undefined and difficult to evaluate in a convenient and objective way. In this article, we describe the development of the Automatic Website Evaluation System (AWES), an automated website evaluation tool. AWES is applied to 61 Hong Kong hotel websites. HTML tags representing categories of the information pertinent to effective website design are automatically collected and classified. The results can provide objective and quantitative guidance to website design. [ABSTRACT FROM AUTHOR]

The use of conventional surfactants and defoamers in waterborne coatings can often create an undesirable cycle, whereby each imparts a negative effect that requires the other to solve. Molecular defoamers represent a novel class of defoamers that break foam on a molecular level, which is unlike conventional defoamers that utilize macroscopic physical incompatibility within a coating formulation. This is accomplished by the ability of the molecular defoamer to adsorb at the air-water interface of a foam bubble and, thereby, displace some of the surfactants that stabilize the foam. Based on a fundamental understanding of the effects of basic adsorption parameters, innovative nonsilicone molecular defoamers were developed that provide long-term foam control, effectively reduce both surface tension and foam in a variety of emulsion polymers, and decrease significantly the level of defects in waterborne coating applications. A synergistic performance benefit was obtained when these molecular defoamers were used in combination in an acrylic, industrial maintenance formulation. [ABSTRACT FROM AUTHOR]

Since the completion of the sequencing of the human genome, scientific focus has shifted from studying genes to analysing the much larger number of proteins encoded by them. Several proteins can be generated from a single gene depending on how the genetic information is read (transcribed) and how the resultant protein is modified following translation (post-translational modification). Genomic and proteomic technologies are already providing useful information about autoimmune disease, and they are likely to lead to important discoveries within the next decade. [ABSTRACT FROM AUTHOR]

We have developed a multiplexed reverse phase protein (RPP) microarray platform for simultaneous monitoring of site-specific phosphorylation of numerous signaling proteins using nanogram amounts of lysates derived from stimulated living cells. We first show the application of RPP microarrays to the study of signaling kinetics and pathway delineation in Jurkat T lymphocytes. RPP microarrays were used to profile the phosphorylation state of 62 signaling components in Jurkat T cells stimulated through their membrane CD3 and CD28 receptors, identifying a previously unrecognized link between CD3 crosslinking and dephosphorylation of Raf-1 at Ser259. Finally, the potential of this technology to analyze rare primary cell populations is shown in a study of differential STAT protein phosphorylation in interleukin (IL)-2-stimulated CD4+CD25+ regulatory T cells. RPP microarrays, prepared using simple procedures and standard microarray equipment, represent a powerful new tool for the study of signal transduction in both health and disease. [ABSTRACT FROM AUTHOR]

Investigates the effect of human papillomavirus (HPV) DNA from the E6-E7 region on the integrity of DNA in blastocyst stage embryonic cells. Disruption of blastocysts DNA by the presence of HPV DNA; Association of the intensity of DNA damage with the type of HPV; Modification of comet assay for fixed blastocyst cells.

This paper presents a technology which allows for the existence of mixed traffic, as a first step towards intelligent transport systems. We begin by designing an automatic driving controller called the intelligent vehicle driving system (IVDS). This is a two-layer system: the higher layer analyzes the current scenario and infers the control objective that associates with a certain index function; the lower layer optimizes the function provided by the upper layer. IVDS only uses the measurement of a vehicle's speed and distance relative to the vehicle in front, together with measurements of the vehicle's own state. Consequently, the vehicles equipped with the IVDS can operate together with manually-controlled vehicles. Next, a mathematical rule-based model for human drivers is developed. This model attempts to mimic human driver's behavior in vehicle following and lane-changing. Finally, we examine the control performance of the proposed controller and the potential benefits of mixed traffic by implementing the human driver model and IVDS on an automated highway simulator. [ABSTRACT FROM AUTHOR]

Purpose Of Review: We reviewed research on computer-assisted cognitive-behavior therapy (CCBT) and mobile applications with the goals of assessing the effectiveness of these newer methods of delivering or augmenting treatment and making recommendations on the clinical use of computer tools in psychotherapy of depression and anxiety.Recent Findings: Research on CCBT has found solid evidence for efficacy when the use of a therapeutic computer program is supported by a clinician or other helping professionals. Lower levels of efficacy or ineffectiveness typically have been found when computer programs are used as stand-alone treatments. A large number of mobile apps have been created that claim to be useful for depression and/or anxiety. However, considerable caution is warranted in evaluating mobile apps and recommending them to patients. Research on mobile apps is still in an early stage of development. A number of well-established CCBT programs have been studied in multiple randomized, controlled trials and have been found to be effective. Such programs appear to have adequate quality, security, and efficacy to be used in clinical practice. Mobile apps offer easy portability and immediate access to coping strategies and may be useful for augmenting treatment. But clinicians need to select apps with integrity and reliable content for clinical use. [ABSTRACT FROM AUTHOR]

Purpose Of Review: Mental health clinicians should understand how technologies augment, enhance, and provide alternate means for the delivery of mental healthcare. These technologies can be used asynchronously, in which the patient and the clinician need not be communicating at the same time. This contrasts with synchronous technologies, in which patient and clinician must communicate at the same time.Recent Findings: The review is based on research literature and the authors' clinical and healthcare administration experiences. Asynchronous technologies can exist between a single clinician and a single patient, such as patient portal e-mail and messaging, in-app messaging, asynchronous telepsychiatry via store-and-forward video, and specialty patient-to-provider mobile apps. Asynchronous technologies have already been used in different countries with success, and can alleviate the psychiatric workforce shortage and improve barriers to access. Multiple studies referred to in this review demonstrate good retention and acceptability of asynchronous psychotherapy interventions by patients. Asynchronous technologies can alleviate access barriers, such as geographical, scheduling, administrative, and financial issues. It is important for clinicians to understand the efficacy, assess the ethics, and manage privacy and legal concerns that may arise from using asynchronous technologies. [ABSTRACT FROM AUTHOR]

Two genes are synthetically lethal (SL) when defects in both are lethal to a cell but a single defect is non-lethal. SL partners of cancer mutations are of great interest as pharmacological targets; however, identifying them by cell line-based methods is challenging. Here we develop MiSL (Mining Synthetic Lethals), an algorithm that mines pan-cancer human primary tumour data to identify mutation-specific SL partners for specific cancers. We apply MiSL to 12 different cancers and predict 145,891 SL partners for 3,120 mutations, including known mutation-specific SL partners. Comparisons with functional screens show that MiSL predictions are enriched for SLs in multiple cancers. We extensively validate a SL interaction identified by MiSL between the IDH1 mutation and ACACA in leukaemia using gene targeting and patient-derived xenografts. Furthermore, we apply MiSL to pinpoint genetic biomarkers for drug sensitivity. These results demonstrate that MiSL can accelerate precision oncology by identifying mutation-specific targets and biomarkers. [ABSTRACT FROM AUTHOR]

The use of video-based telepsychiatry is increasing in response to consumer demand for convenient, inexpensive, and readily accessible services; improved financial reimbursement; and a robust body of evidence-based literature. Telepsychiatry leads to high patient and provider satisfaction ratings, and outcomes equivalent to in-person care, while younger generations often prefer telepsychiatry over face-to-face encounters. The evidence base for telepsychiatry is especially strong with respect to the treatment of post-traumatic stress disorder (PTSD), depression, and ADHD, while its use in underserved ethnic groups is well described in the American Indian, Hispanic, and Asian populations. Despite this, telepsychiatry barriers still persist. These include personal bias-especially in leadership-and insufficient training; the challenging business environment and legislative processes; and inconsistent reimbursement, licensing, and prescription policies. Technology is now less of a barrier, and it is clear that telepsychiatry overall is flourishing and changing the way that providers are working and patients are being treated. [ABSTRACT FROM AUTHOR]