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A photo/electrothermal surface can convert sunlight and electricity into heat to solve icing problems. The combination of active photo/electrothermal surfaces with passive slippery surfaces provides a highly efficient strategy for all-day anti/deicing. However, the lack of transparency remains a primary impediment to the widespread application of these anti-icing measures in photovoltaics, windshields, and other fields. Herein, we report a bilayer transparent photo/electrothermal coating with a liquid-like slippery property for all-day anti/deicing. The prepared coating exhibits ultraslippery, low ice adhesion, and enhanced stability properties through covalent grafting of polydimethylsiloxane (PDMS) brushes in a cross-linked skeleton of epoxy. Moreover, the coating demonstrates a visible transmittance of up to 77% and effectively absorbs ultraviolet and near-infrared light due to the addition of ultraviolet and infrared absorbers, resulting in a temperature increase under sun illumination. The bottom indium tin oxide layer is fabricated to provide the composite coating with electrothermal capability, so that it can achieve all-weather deicing. The coupling of photo/electrothermal and slippery properties can promote the rapid removal of grown ice in a short time. The slippery properties and their exceptional durability under mechanical, optical, and thermal conditions render the composite coatings highly promising for engineering applications.

In oviparous animals, egg yolk is largely derived from vitellogenin, which is taken up from the maternal circulation by the growing oocytes via the vitellogenin receptor. Recently, a novel member of the lipoprotein receptor superfamily termed low-density lipoprotein receptor-related protein 13 was identified and proposed as a candidate of vitellogenin receptor in oviparous animals. However, the roles of low-density lipoprotein receptor-related protein 13 in vitellogenesis are still poorly defined. Here, we investigated the expression, vitellogenin-binding properties, and function of low-density lipoprotein receptor-related protein 13 in zebrafish. Two different lrp13genes termed lrp13aand lrp13bwere found in zebrafish. Reverse transcription polymerase chain reaction and quantitative polymerase chain reaction revealed both lrp13sto be predominantly expressed in zebrafish ovary, and in situ hybridization detected both lrp13stranscripts in the ooplasm of early stage oocytes. Two yeast hybrid studies showed that among eight vitellogenins of zebrafish, Vtg1, 2, and 3 bind to Lrp13a, while Vtg1, 2, and 5 bind to Lrp13b. We created zebrafish lrp13aand lrp13bmutant lines using CRISPR/Cas9. Knockout of lrp13aleads to a male-biased sex ratio and decreased diameter of embryo yolk, while knockout of lrp13band double knockout of lrp13aand lrp13bleads to the delay of vitellogenesis, followed by follicular atresia. These phenotypes of mutants can be explained by the disruption of vitellogenesis in the absence of Lrp13s. Taken together, our results indicate that both Lrp13a and Lrp13b can serve as vitellogenin receptors in zebrafish among other vitellogenin receptors that are not yet described.Both Lrp13a and Lrp13b serve as vitellogenin receptors in the ovary of zebrafish.Graphical Abstract

Real-World Evidence (RWE), which has historically been used to support post-approval safety studies, has recently gained acceptance for new drug applications as supportive evidence or as new clinical evidence for medicinal products with orphan designation and/or in disease areas with high unmet need. Here, we present a case study for the use of RWE in the approval of abaloparatide in the European Union (EU) under the tradename Eladynos. In addition to data from the pivotal Phase 3 study, the marketing authorization application (MAA) included clinical data from additional interventional and observational studies, as well as post-marketing data obtained from the United States (US) market since approval of abaloparatide by the Food and Drug Administration (FDA) in 2017. The new interventional studies were not designed to assess fracture efficacy and cardiovascular safety which were topics of concern raised by the Committee for Medicinal Products for Human Use (CHMP) during their review of the initial MAA submitted in 2015. However, these studies taken together with the RWE formed the basis for a new MAA. Prior to the planned resubmission in the EU, national Scientific Advice (SA) was sought on the proposed clinical program, specifically on the relevance of Real-World Data (RWD) derived from an observational study to support and complement the efficacy and safety data already available from prospective randomized clinical trials. This case study demonstrates successful use of RWE to address a previously identified gap raised by the CHMP during the review of an earlier MAA, which led to the approval of Eladynos for the treatment of osteoporosis in the EU.

Background: Osteoporotic-related fractures represent an increasing burden to patients, health care systems and society. Aims: This study estimated cost-effectiveness of sequential treatment with abaloparatide (ABL) followed by alendronate (ALN) compared to relevant alternative strategies in US men and women aged 50 to 80 years at very high fracture risk (bone mineral density T-score ≤  − 2.5 and a recent fracture). Methods: A lifetime Markov-based microsimulation model was used to estimate healthcare costs and quality-adjusted life years (QALYs). Comparators were sequential treatment with unbranded teriparatide (TPTD)/ALN, generic ALN monotherapy, and no treatment. Analyses were conducted based on initial fracture site (hip, vertebral, or any fracture) and treatment efficacy data (derived from clinical trials or a recent network meta-analysis). Results: From all analyses completed, sequential ABL/ALN demonstrated more QALYs for lower healthcare costs versus unbranded TPTD/ALN. No treatment was dominated (higher costs for less QALYs) versus ALN monotherapy. Sequential ABL/ALN resulted in favorable cost-effectiveness (at US threshold of $150,000/QALY) versus generic ALN monotherapy in men aged ≥ 50 years with any fracture type, women aged ≥ 65 years with any fracture type, and women aged ≥ 55 years having a hip or vertebral fracture. Discussion: Similar cost-effectiveness of sequential ABL/ALN versus unbranded TPTD/ALN, ALN monotherapy, and no treatment was observed in both US men and women at very high fracture risk, with a moderate improvement in cost-effectiveness in men versus women and in patients with a hip or vertebral fracture. Conclusions: Sequential therapy with ABL/ALN was cost-effective in US men and women at very high risk of fractures.

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The popularity of humidity sensing for respiratory analysis of patients is gradually increasing because of its portability and cost-effectiveness. However, current flexible humidity sensors are mainly made of polymer films, whose poor hygroscopicity and breathability reduce their sensitivity and comfort. In this study, a highly sensitive humidity sensor was developed using non-woven fabric (NWF) coated with graphene oxide (GO). Bovine serum albumin was used to improve the adsorption of GO onto the NWF, and its effect on sensitivity was investigated by adjusting its concentration. High-humidity sensitivity was experimentally validated by testing different relative humidity levels, and its fast response and excellent feasibility under diverse breathing conditions were verified by successful monitoring of fast and deep breathing, differentiating nose and mouth breathing, and even identifying simple spoken words. This study developed a breathable and skin-friendly humidity sensor based on GO/NWF, which is a promising device for human healthcare.

The design and preparation of effective nonprecious metal-based catalysts for the urea oxidation reaction (UOR) coupled with the hydrogen evolution reaction (HER) are of great significance to solve both energy shortage and environmental pollution problems. In this study, a novel hierarchical superhydrophilic and superaerophobicity three-dimensional nanorod-like bifunctional catalyst with a heterostructure (Ni3S2/VS2) was prepared on nickel foam via a simple one-step hydrothermal method, serving as an excellent electrocatalyst for both UOR and HER. The formed heterostructure significantly alters the electronic structure, optimizing charge transfer and increasing the number of active sites, which enhances the electrocatalytic performance of Ni3S2/VS2. As a result, this catalyst requires an extremely low potential of 1.396 V at the current density of 100 mA cm–2for UOR and only 164 mV overpotential at −10 mA cm–2for HER. Notably, a constructed two-electrode electrolyzer system (Ni3S2/VS2∥Ni3S2/VS2) demonstrates extraordinary activity and long-term stability, achieving a current density of 10 mA cm–2at a low cell voltage of 1.48 V, which is superior to majority of the reported catalysts. This work demonstrates that the formation of heterostructures can effectively enhance the catalytic activity of nanomaterials toward UOR and HER and provides a feasible strategy for fabricating highly efficient nonprecious metal overall urea electrocatalysts.

A three-dimensional rGO network encapsulating Na3V2(PO4)2F3nanocuboids was constructed to accelerate electron and Na+transport, while restricting the volume change of Na3V2(PO4)2F3during charge and discharge processes, thereby showing greatly enhanced high-rate performance and cyclability.

Liquid-solid based triboelectric nanogenerator (TENG) can be widely utilized for droplet energy harvesting, in which the hydrophobicity of triboelectric layer is crucial for output enhancement. However, poor mechanical properties of hydrophobic triboelectric layers prepared in classic methods greatly limit the TENG’s application. Here, a stretchable hydrophobic triboelectric nanogenerator (SH-TENG) with excellent output, and durability is devised by strongly bonding PTFE micro particles on a flexible substrate even under extreme stretching or abrasion. By synergistic enhancement of the PTFE particles on both contact-separation and charge-transfer between droplet and triboelectric layer, the transfer charge density of SH-TENG is increased to ∼4.74 × 10−3C/m2·L, along with the open circuit voltage (VOC) and short circuit current (ISC) over 7 times and 6 times higher than TENG without PTFE modified, respectively. Moreover, under a stretching rate of 500%, the SH-TENG shows less 20% decline of its output performance to guarantee applications in flexible electronics. A miniature watch can be sufficiently powered by the SH-TENGs with total area of 0.016 m2under the simulated raindrop flow rate of 50 mL/min. With such outstanding performance and environmental adaptability, the SH-TENG can be integrated with various objects to collect droplet energy and supply electronic devices.

Background:The US Food and Drug Administration has recently approved abaloparatide (ABL) for treatment of women with postmenopausal osteoporosis (PMO) at high risk of fracture. With increasing health care spending and drug prices, it is important to quantify the value of newly available treatment options for PMO. Objective:To determine cost-effectiveness of ABL compared with teriparatide (TPTD) for treatment of women with PMO in the United States. Methods:A discrete-event simulation (DES) model was developed to assess cost-effectiveness of ABL from the US health care perspective. The model included three 18-month treatment strategies with either placebo (PBO), TPTD, or ABL, all followed by additional 5-year treatment with alendronate (ALN). High-risk patients were defined as women with PMO ⩾65 years old with a prior vertebral fracture. Baseline clinical event rates, risk reductions, and patient characteristics were based on the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial. Results:Over a 10-year period, the DES model yielded average total discounted per-patient costs of $10 212, $46 783, and $26 837 and quality-adjusted life-years (QALYs) of 6.742, 6.781, and 6.792 for PBO/ALN, TPTD/ALN, and ABL/ALN, respectively. Compared with TPTD/ALN, ABL/ALN accrued higher QALYs at lower cost and produced an incremental cost-effectiveness ratio (ICER) of $333 266/QALY relative to PBO/ALN. In high-risk women, ABL/ALN also had more QALYs and less cost over TPTD/ALN and yielded an ICER of $188 891/QALY relative to PBO/ALN. Conclusion and Relevance:ABL is a dominant treatment strategy over TPTD. In women with PMO at high risk of fracture, ABL is an alternative cost-effective treatment.

Introduction There are limited data on the management of bone health, including bone mineral density (BMD) evaluation and osteoporosis (OP) treatment, in patients undergoing elective orthopaedic surgeries.Methods This was a retrospective cohort study using administrative claims data from Symphony Health, PatientSource for patients aged ≥50 years with documented kyphoplasty/vertebroplasty (KP/VP), total knee arthroplasty (TKA), and total hip arthroplasty (THA). Risk stratification to identify patients at very high risk for fracture (VHRFx) was based on clinical practice guideline recommendations to the extent information on variables of interest were available from the claims database.Results A total of 251 919 patients met inclusion criteria: KP/VP (31 018), TKA (149 849), and THA (71 052). The majority were female (80.3%) with a mean (SD) age of 68.5 (7.5) years. Patients undergoing KP/VP were older and had a greater comorbidity burden associated with risk for falls, mobility issues, muscle weakness, and respiratory and cardiovascular diseases. In the 6 months before surgery, 11.8% of patients were tested and/or received treatment for OP. Patients undergoing KP/VP were more likely to be tested and/or treated (17.5%) than patients undergoing TKA (11.0%) or THA (10.9%). Overall, men had a lower rate of testing and/or treatment than women (4.6% vs 13.5%). In the 12 months before surgery, patients with an OP diagnosis and at VHRFx (30.8%) had a higher rate of treatment and/or testing than those without OP (11.5%), or those without OP but with a fracture in the year preceding surgery (10.2%).Conclusions Bone health management is suboptimal in patients undergoing elective orthopaedic surgeries and is worse in men than in women. Proper management of OP before and after surgery may improve outcomes.

Objective Continuous renal replacement therapy (CRRT) is well suited for treating metabolic abnormalities and renal insufficiency associated with tumour lysis syndrome (TLS). However, there is controversy regarding the choice of time for CRRT, the selection of CRRT models, and methods of decreasing complications of CRRT. This study aimed to evaluate the efficacy and outcomes of daytime continuous veno-venous haemofiltration (CVVH) for treating paediatric TLS.Methods The clinical features, technique-related complications, and prognosis were prospectively analysed in eight paediatric patients with TLS who were supported by daytime CVVH in West China Second University Hospital, Sichuan University from January 2007 to July 2016.Results Seven patients were boys and one was a girl. All of the patients had hyperphosphataemia, and there were four cases of hyperkalaemia, four cases of hyperuricaemia, and two cases of hypocalcaemia. All of the patients received one to 10 CVVH treatments. Urine output, renal function, serum uric acid levels, and potassium, phosphate, and calcium levels returned to normal in all of the patients, but recovery of renal function was relatively slow. No significant adverse reactions were observed. All of the patients recovered and were discharged.Conclusion Daytime CVVH is a safe and effective treatment for paediatric TLS.

Immunoglobulin A nephropathy (IgAN) is the most frequent pathological diagnosis of tuberculosis (TB)-associated glomerulonephritis. Diagnosing TB-associated IgAN (TB-IgAN) is difficult because of its non-specific and insidious symptoms. An inaccurate diagnosis of TB-IgAN could result in the spread of TB and reduced renal function. Haematuria and proteinuria in conjunction with TB should be assessed because of the potential for diagnosis of IgAN. Renal biopsy is important in securing an accurate diagnosis prior to initiating treatment. Detection of Mycobacterium tuberculosisDNA and assessment of early secreted antigenic target of 6 kDa in renal biopsy tissues may have great potential diagnostic value in patients with TB-IgAN. Anti-TB therapy can effectively alleviate TB and TB-IgAN.

Wheat (Triticum aestivum) is among the most important staple crops for safeguarding the food security of the growing world population. To bridge the gap between genebank diversity and breeding programs, we developed an advanced backcross–nested association mapping plus inter-crossed population (AB–NAMIC) by crossing three popular wheat cultivars as recurrent founders to 20 germplasm lines from a mini core collection. Selective backcrossing combined with selection against undesirable traits and extensive crossing within and between sub-populations created new opportunities to detect unknown genes and increase the frequency of beneficial alleles in the AB–NAMIC population. We performed phenotyping of 590 AB–NAMIC lines and a natural panel of 476 cultivars for six consecutive growing seasons and genotyped these 1066 lines with a 660K SNP array. Genome-wide association studies of both panels for plant development and yield traits demonstrated improved power to detect rare alleles and loci with medium genetic effects in AB–NAMIC. Notably, genome-wide association studies in AB–NAMIC detected the candidate gene TaSWEET6-7B(TraesCS7B03G1216700), which has high homology to the rice SWEET6bgene and exerts strong effects on adaptation and yield traits. The commercial release of two derived AB–NAMIC lines attests to its direct applicability in wheat improvement. Valuable information on genome-wide association study mapping, candidate genes, and their haplotypes for breeding traits are available through WheatGAB (www.wheatgab.com). Our research provides an excellent framework for fast-tracking exploration and accumulation of beneficial alleles stored in genebanks.

To mitigate interference on cell-edge users and improve fairness of the whole system, dynamic inter-cell interference coordination (ICIC) is one of the promising solutions. However, traditional dynamic ICIC is considered as an NP-hard problem and power variability further adds another dimension to this joint optimization issue, making it even more difficult to quickly reach a near-optimal solution. Therefore, we theoretically obtain the closed-form expression of the near-optimal power allocation ratio for users in adjacent cells paired in the same resource block and interfere each other, so that the total utility corresponding to α-fairness is maximized. Dynamic ICIC using this closed-form solution could improve user fairness without causing an increment of the computational complexity. Numerical results show that, compared with the schemes using identical power for different users, our method does not obviously degrade the system's average spectral efficiency.

Purpose: We tested the hypothesis that clevidipine, a rapidly acting dihydropyridine calcium channel blocker, is not inferior to nitroglycerin (NTG) in controlling blood pressure before cardiopulmonary bypass (CPB) during coronary artery bypass grafting (CABG). Methods: In this double-blind study from October 4, 2003 to April 26, 2004, 100 patients undergoing CABG with CPB were randomized at four centres to receive intravenous infusions of clevidipine (0.2-8 μg·kg−1·min−1) or NTG (0.4 μg·kg−1·min−1to a clinician-determined maximum dose rate) from induction of anesthesia through 12 hr postoperatively. The study drug was titrated in the pre-CPB period with the aim of maintaining mean arterial pressure (MAP) within ± 5 mmHg of a clinician-predetermined target. The primary endpoint was the area under the curve (AUC) for the total time each patient’s MAP was outside the target range from drug initiation to the start of CPB, normalized per hour (AUCMAP-D). The predefined non-inferiority criterion for the primary endpoint was a 95% confidence interval (CI) upper limit no greater than 1.50 for the geometric means ratio between clevidipine and NTG. Results: Total mean [standard deviation (SD)] dose pre-bypass was 4.5 (4.7) mg for clevidipine and 6.9 (5.4) mg for NTG (P< 0.05). The geometric mean AUCMAP-Dfor clevidipine was 283 mmHg·min·hr−1(n= 45) and for NTG was 292 mmHg·min·hr−1(n= 48); the geometric means ratio was 0.97 (95% CI 0.74 to 1.27). The geometric mean AUCMAP-Dduring aortic cannulation was 357.7 mmHg·min·hr−1for clevidipine compared with 190.5 mmHg·min·hr−1for NTG. Mean (SD) heart rate with clevidipine was 76.0 (13.8) beats·min−1compared with 81.5 (14.4) beats·min−1for NTG. There were no clinically important differences between groups in adverse events. Conclusion: During CABG, clevidipine was not inferior to NTG for blood pressure control pre-bypass.

Background:Perioperative hypertension affects 80% of cardiac surgery patients and is associated with an increased risk of complications.Objective:To determine the relationship between perioperative blood pressure (BP) control and hospital costs for cardiac surgery in the United States (US) and estimate the potential cost reductions associated with effective therapies.Methods:The analysis estimated hospitalization costs (2011 US dollars (USD)) for cardiac surgery when BP was controlled with intravenous (IV) antihypertensives. Patient characteristics, hospital length of stay, and clinical event rates during the initial hospitalization and post-discharge 30 days after study drug infusion were based on the ECLIPSE (Evaluation of CLevidipine In the Perioperative Treatment of Hypertension Assessing Safety Events) trials. These clinical trial data were combined with data from the Massachusetts Acute Hospital Case Mix Database 2007 – 2009 (MA Case Mix Database) to estimate total hospitalization costs.Results:Effective perioperative BP control in patients requiring IV antihypertensives was associated with a 7% decrease in hospital costs compared with less effective BP control. Reductions in total hospital costs associated with clevidipine versus other IV antihypertensives averaged 394 per patient overall. Cost savings with clevidipine exceeded 500 per patient versus sodium nitroprusside and nitroglycerin, but only 22 compared to nicardipine.Conclusion:Improved perioperative BP control may reduce hospital costs. Given the low cost of IV antihypertensives, the total hospital cost reductions may offset any incremental cost increases associated with newer, more effective therapies.

The interaction between Dma1 and Dnt1 in fission yeast is characterized. The results show that, similar to its homologue Chfr in higher eukaryotes, Dma1 in fission yeast can also affect factors required for microtubule nucleation and spindle formation at early mitosis.

In fission yeast Schizosaccharomyces pombe, a diploid mother cell differentiates into an ascus containing four haploid ascospores following meiotic nuclear divisions, through a process called sporulation. Several meiosis-specific proteins of fission yeast have been identified to play essential roles in meiotic progression and sporulation. We report here an unexpected function of mitotic spindle checkpoint protein Dma1 in proper spore formation. Consistent with its function in sporulation, expression of dma1+is up-regulated during meiosis I and II. We showed that Dma1 localizes to the SPB during meiosis and the maintenance of this localization at meiosis II depends on septation initiation network (SIN) scaffold proteins Sid4 and Cdc11. Cells lacking Dma1 display defects associated with sporulation but not nuclear division, leading frequently to formation of asci with fewer spores. Our genetic analyses support the notion that Dma1 functions in parallel with the meiosis-specific Sid2-related protein kinase Slk1/Mug27 and the SIN signaling during sporulation, possibly through regulating proper forespore membrane assembly. Our studies therefore revealed a novel function of Dma1 in regulating sporulation in fission yeast.

By characterizing the fission yeast Dma1's function during meiosis, we revealed that Dma1 is required for spore formation, while it is dispensable for fidelity of nuclear divisions. We also found that Dma1 is functionally related to SIN pathway and meiosis-specific kinase Slk1 during sporulation.

Germplasm conserved in gene banks is underutilized, owing mainly to the cost of characterization. Genomic prediction can be applied to predict the genetic merit of germplasm. Germplasm utilization could be greatly accelerated if prediction accuracy were sufficiently high with a training population of practical size. Large-scale resequencing projects in rice have generated high quality genome-wide variation information for many diverse accessions, making it possible to investigate the potential of genomic prediction in rice germplasm management and exploitation. We phenotyped six traits in nearly 2000 indica(XI) and japonica(GJ) accessions from the Rice 3K project and investigated different scenarios for forming training populations. A composite core training set was considered in two levels which targets used for prediction of subpopulations within subspecies or prediction across subspecies. Composite training sets incorporating 400 or 200 accessions from either subpopulation of XI or GJ showed satisfactory prediction accuracy. A composite training set of 600 XI and GJ accessions showed sufficiently high prediction accuracy for both XI and GJ subspecies. Comparable or even higher prediction accuracy was observed for the composite training set than for the corresponding homogeneous training sets comprising accessions only of specific subpopulations of XI or GJ (within-subspecies level) or pure XI or GJ accessions (across-subspecies level) that were included in the composite training set. Validation using an independent population of 281 rice cultivars supported the predictive ability of the composite training set. Reliability, which reflects the robustness of a training set, was markedly higher for the composite training set than for the corresponding homogeneous training sets. A core training set formed from diverse accessions could accurately predict the genetic merit of rice germplasm.

It is an important project for present tectonics, to precisely research the time and space of detachment formation in the lithosphere, in geological history. According to collect a lot of collected data of on the magmatic source depths for of Eastern China during Yanshanian (205–135 Ma) and Sichuanian (135–52 Ma) tectonic stages, it is a suitable to roughly determine the local tectonic detachment, partial decoupling decoupling, and interaction between spheres in the lithosphere or at the bottom of the lithosphere. The results showed that the tectonic detachment, partial decoupling decoupling, and interaction between spheres were are exhibited and concentrated at the intersections among among the middle crust, Moho discontinuity, and regional main faults of Eastern China. During the Yanshanian and Sichuanian tectonic stages, however, obvious detachment or migration in those stages at the bottom of the lithosphere does not exist obvious detachment or migration in those stages. The violent magmatic area of Eastern China during the Jurassic and Cretaceous are mainly distributed east to of the boundary of Dahingganling–western Shanxi–Wulingshan–Siwandashan, and to the west to of this boundary the magmatism was is very weak. The authors propose that there was is a continental type of lithosphere at the west to of that boundary, and oceanic-continental transition type of lithosphere (continental crust with oceanic lithospheric mantle) at to the east to of that boundary. The lithosphere transformation and thinning of in Eastern China, in the Jurassic probably resulteded neitherfrom from the mantle plume, un-rooting, upsurge of heat mantle materials, and continental rifting,, nor directly from the subduction of the Pacific plate.

Introduction Myelodysplastic syndromes (MDS) are a group of heterogeneous bone marrow clonal diseases characterized by the abnormal differentiation and development of bone marrow cells. Src homology region 2 domain-containing phosphatase (SHP)-1 is an important tumor suppressor gene that regulates the signal transducer and activator of transcription (STAT) pathway.Methods Survival analysis was performed to evaluate the function of decitabine (5-Aza) in treating MDS patients with and without SHP-1 methylation. The effects of 5-Aza treatment on SHP-1 expression and methylation and STAT3 phosphorylation were investigated in MDS cells by methylation-specific PCR, reverse transcription PCR, and western blotting. Cell viability and apoptosis were similarly evaluated by MTT assay and flow cytometry.Results High-risk MDS patients showed significant SHP-1 hypermethylation compared with low-risk patients, and patients with no SHP-1 methylation had longer overall survival. SHP-1 expression was significantly increased at mRNA and protein levels following 5-Aza treatment, while the phosphorylation of STAT3 protein was significantly decreased. Apoptosis increased significantly in MDS cells treated with higher doses of 5-Aza while cell viability decreased significantly.Conclusion SHP-1 hypermethylation was associated with poor prognosis in HR patients with MDS, suggesting it could be used as a prognostic indicator.

Background Osteoporosis-related fractures are an important public health burden.Objective To examine health care costs in Medicare patients with an osteoporosis-related fracture.Methods Medicare fee-for-service members with an osteoporosis-related fracture between January 1, 2010, to September 30, 2014 were included. A nonfracture comparator group was selected by propensity score matching. Generalized linear models using a gamma distribution were used to compare costs between fracture and nonfracture cohorts.Results A total of 885 676 Medicare beneficiaries had fracture(s) and met inclusion criteria. Average age was 80.5 (±8.4) years; 91% were White, and 94% female. Mean all-cause costs were greater in the fracture vs nonfracture cohort ($47 163.25 vs $16 034.61) overall and for men ($52 273.79 vs $17 352.68). The highest mean costs were for skilled nursing facility ($29 216), inpatient costs ($24 190.19), and hospice care ($20 996.83). The highest incremental costs versus the nonfracture cohort were for hip ($71 057.83 vs $16 807.74), spine ($37 543.87 vs $16 860.49), and radius/ulna ($24 505.27 vs $14 673.86). Total medical and pharmacy costs for patients who experienced a second fracture were higher compared with those who did not ($78 137.59 vs $44 467.47). Proportionally more patients in the fracture versus nonfracture cohort died (18% vs 9.3%), with higher death rates among men (20% vs 11%).Conclusion and Relevance The current findings suggest a significant economic burden associated with fractures. Early identification and treatment of patients at high risk for fractures is of paramount importance for secondary prevention and reduced mortality.

•A significantly greater proportion of abaloparatide/alendronate patients had BMD increases over 0, 3 and 6 percent versus placebo/alendronate.•BMD responses were higher at all anatomic sites and for all thresholds assessed for abaloparatide/alendronate versus placebo/alendronate•This study provides further evidence of cumulative benefit from sequential treatment with an anabolic agent followed by an antiresorptive.

Introduction:Elevated blood pressure (BP) is associated with increased risk of neurologic decline and poor outcome in acute ischemic stroke (AIS). The American Stroke Association (ASA) recommends antihypertensive (AH) therapy if BP is >220120 mmHg, with a goal of 15-25 reduction in the first 24 hours. In thrombolytic candidates, BP should be maintained 185110 mmHg for 24 hours after rt-PA. Labetalol and nicardipine are the recommended parenteral (IV) agents. We sought to characterize the use of IV AHs in the first 24 hours after AIS admission, stratified by treatment with rt-PA.