High Target Research Articles

983-P: First Home Evaluation of the Omnipod Horizon Automated Glucose Control System at Specific Glucose Targets in Adults with Type 1 Diabetes

The Omnipod Horizon™ System is a hybrid closed-loop system (HCL) consisting of a tubeless insulin pump and Dexcom G6 sensor which provides automated insulin delivery with customizable glucose targets from 110-150mg/dL, adjustable by time of day to allow therapy personalization. This outpatient study assessed the safety and effectiveness of HCL use at higher targets of 130-150mg/dL. Participants aged 14-70y with T1D>6mo and A1C<10.0% used the HCL system at home for 14 days (first 2 days hotel, n=8) over winter holidays with unrestricted eating and exercise. The target was 130, 140, and 150mg/dL for 3 days each, followed by 5 days of free choice of 110-150mg/dL. Primary outcomes were safety measures and percent time 70-180mg/dL over the first 9 days of HCL, stratified by target glucose. Participants thus far (n=13) had a mean±SD age of 35±13y, T1D duration 16±13y, and A1C 6.9±0.8%. At the 130, 140, and 150mg/dL targets, percent time from 70-180mg/dL was 75.6±11.6%, 66.5±8.9%, and 63.7±7.9%, respectively (Table). Percent time <54 and <70mg/dL decreased with increasing target, without a corresponding increase in time ≥250 mg/dL. There were no serious adverse events. The HCL system was safe and performed well in adults with T1D when used at home with higher glucose targets. Participants were invited to continue in a 3mo outpatient study of the system, which is currently underway. Disclosure S.A. Brown: Research Support; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Tolerion, Inc. B.W. Bode: Advisory Panel; Self; InPen, Medtronic. Consultant; Self; ADOCIA, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Pfizer Inc. Research Support; Self; Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Medtronic, Novo Nordisk A/S, Provention Bio, Inc., Senseonics, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., InPen, Janssen Pharmaceuticals, Inc., MannKind Corporation, Medtronic, Novo Nordisk A/S, Sanofi, Sanofi, Senseonics, Xeris Pharmaceuticals, Inc. Stock/Shareholder; Self; Glytec. C.J. Levy: Consultant; Self; Dexcom, Inc. Employee; Spouse/Partner; Allergan plc. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation. G.P. Forlenza: Advisory Panel; Self; Medtronic. Consultant; Self; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Medtronic. Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. A.B. Criego: Other Relationship; Self; Dexcom, Inc., Lilly Diabetes, Medtronic, Omnipod. T.T. Ly: Employee; Self; Insulet Corporation. Funding Insulet Corporation

984-P: First Home Evaluation of the Omnipod Horizon Automated Glucose Control System in Adults with Type 1 Diabetes

The Omnipod Horizon™ System is a hybrid closed-loop system (HCL) consisting of a tubeless insulin pump and Dexcom G6 sensor which provides automated insulin delivery with glucose targets from 110-150mg/dL, adjustable by time of day to allow therapy personalization. This study is the first outpatient safety and effectiveness evaluation of the system. Participants aged 14-70y with T1D>6mo and A1C<10.0% used the HCL system at home for 14 days (first 2 days hotel, n=8) over winter holidays with unrestricted eating and exercise. Participants set protocol-determined higher targets of 130-150mg/dL for 9 days, then could freely choose their targets from 110-150mg/dL for the last 5 days. Primary outcomes were safety measures and percent time 70-180mg/dL for the 5 days of HCL use with free choice of target. Participants thus far (n=12) had a mean±SD age of 34±13y, T1D duration 15±12y, and A1C 6.9±0.8%. Participants primarily chose the 110 (59% of study time) and 120mg/dL (41%) targets. For 53 patient-days of HCL use, percent time from 70-180mg/dL was 74.3±7.6% (Table). Percent time <70mg/dL was low: 0.9±1.3% overall and 0.9±2.2% overnight. There were no serious adverse events. The HCL system was safe and performed well in adults with T1D when used at home for 5 days with free choice of target glucose. Participants were invited to continue in a 3mo outpatient study of the system, which is currently underway. Disclosure S.A. Brown: Research Support; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Tolerion, Inc. B.W. Bode: Advisory Panel; Self; InPen, Medtronic. Consultant; Self; ADOCIA, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Pfizer Inc. Research Support; Self; Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Medtronic, Novo Nordisk A/S, Provention Bio, Inc., Senseonics, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., InPen, Janssen Pharmaceuticals, Inc., MannKind Corporation, Medtronic, Novo Nordisk A/S, Sanofi, Sanofi, Senseonics, Xeris Pharmaceuticals, Inc. Stock/Shareholder; Self; Glytec. C.J. Levy: Consultant; Self; Dexcom, Inc. Employee; Spouse/Partner; Allergan plc. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation. G.P. Forlenza: Advisory Panel; Self; Medtronic. Consultant; Self; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Medtronic. Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. A.B. Criego: Other Relationship; Self; Dexcom, Inc., Lilly Diabetes, Medtronic, Omnipod. T.T. Ly: Employee; Self; Insulet Corporation. Funding Insulet Corporation

49-LB: “You Don’t Know When the Sugar’s Going to Kick In”: Experiences of People Managing Type 1 Diabetes during a Marathon

There are many benefits of regular exercise in diabetes, but people with type 1 diabetes (T1D) also have the risk of short-term complications. There is a lack of research and information about how individuals with T1D should prepare and recover from endurance exercise. The present study had two primary objectives: 1) Understand how previous runners experienced participating in a marathon and 2) Understand their experience managing their diabetes while training for and recovering from a marathon. The study included 10 participants who had previously participated in the New York City Marathon with the Beyond Type 1 Team (mean age 33.3 ± 12.9 years, duration of T1D 13.2 ± 14.8 years, A1c 6.59 ± .7%), 80% female, 90% on insulin pump and 100% on CGM. Interviews were transcribed and thematically analyzed. Themes included (but are not limited to): methods to maintain euglycemia, preparation to reduce glycemic variability during endurance activities, and managing blood glucose variability during the marathon and recovery period. Diabetes devices were identified as a key theme given how integral they were to marathon preparation and performance. Multiple participants discussed using specific CGM and pump site placement to prevent the devices from falling off. Participants described various strategies to prevent hypoglycemia during their runs (both for training and the marathon). Some participants described frequent disruptions to their training plan due to diabetes and setting a higher target glucose to accommodate for the exercise. This data provides initial insight into the decision-making that occurs for people with T1D who participate in endurance activities - including food preparation, planning ahead for supplies and insulin manipulation, in-the-moment management decisions, and recovery period glucose management. Disclosure A. Hughes: None. J. Bispham: None. L. Fuller: None. A.H. Mcauliffe-Fogarty: None.

Financing Target and Product Line Design on the Flexible and Fixed Reward Crowdfunding

This study examined the product line design under two different types of reward crowdfunding, namely, the fixed and the flexible reward crowdfunding. To investigate different effects of the two different reward crowdfunding mechanisms, we addressed the problem of product and pricing decisions in reward crowdfunding by incorporating individual rationality and incentive compatibility into different funding modes. Specifically, when the creator designed the menu price, we compared the menu design, which includes price and quality between the product line under two different crowdfunding mechanisms. We found that when the quality was exogenous, the project could have higher success rate and get more expected profit under the fixed reward crowdfunding than that under the flexible reward crowdfunding; however, the creator could set a higher target and a larger price discrepancy under the flexible reward crowdfunding in some specific market condition. Then, we extended to the situation where the quality was endogenous and found the similar results as the quality was exogenous. Interestingly, the quality differentiation of the product line under the flexible reward crowdfunding is much more than that under the fixed reward crowdfunding. These results can provide the guideline and suggestion to help the creators design their product line, set the target, and select the suitable modes between the fixed and the flexible reward crowdfunding.

Rationally assembled albumin/indocyanine green nanocomplex for enhanced tumor imaging to guide photothermal therapy

Herein, a novel phototheranostic nanocomplex that is self-assembled from bovine serum albumin (BSA) and indocyanine green (ICG) is developed for enhanced near-infrared (NIR) fluorescence imaging, which benefits the guidance on in vivo cancer photothermal therapy (PTT). The study confirms that the binding of ICG with the bind sits on the albumin will result in improved hydrolytic stability and high photoluminescence quantum yield (PLQY). The ICG loading ratio in the nanocomplex is optimized and confirms the loading ratio of 0.5% ICG to be the optimal content. The optimized ICG–BSA nanocomplex (ICG–BSA NC) possesses a higher PLQY of 16.8% than that of free ICG (2.7%). The high PLQY and efficient passive targeting ability of ICG–BSA NC help improve its in vivo tumor accumulation and NIR fluorescence imaging significantly. Under laser irradiation, efficient PTT with obvious tumor growth suppression on a triple negative breast tumor model can be observed in the ICG–BSA NC treated group.

DBcAMP Rescues the Neurons From Degeneration in Kainic Acid-Injured Hippocampus, Enhances Neurogenesis, Learning, and Memory.

Dibutyryl cyclic adenosine monophosphate (dBcAMP) is a cell-permeable synthetic analog of cyclic adenosine monophosphate (cAMP). Although the elevation of cAMP levels was reported to promote the functional recovery in spinal cord injury, its role in neurogenesis or functional recovery after hippocampal injury is unknown. The objective of the study was to investigate the effects of dBcAMP on learning, memory, and hippocampal neurogenesis in the excitotoxically lesioned hippocampus. An excitotoxic lesion was induced in the hippocampi of 4-month-old male BALB/c mice by injecting 0.25 μg/μl into the lateral ventricles of both sides. The lesioned mice (L) were divided into L+dBcAMP and L+phosphate-buffered saline (PBS) groups. Sham surgery (S) was done by the injection of 1 μl of sterile saline into the lateral ventricles. The sham surgery mice were divided into S+dBcAMP and S+PBS groups. Mice in the L+dBcAMP and S+dBcAMP groups were treated with dBcAMP for 1 week (i.p., 50 mg/kg), whereas mice in the L+PBS and S+PBS groups were treated with PBS. The mice in all groups were subjected to water maze and passive avoidance tests at the end of the 4th week. Cresyl violet staining and NeuN and doublecortin immunostaining were done to analyze the morphology and neurogenesis. The water maze learning sessions did not show a significant difference in escape latency between the groups, suggesting an unimpaired learning ability of mice in all groups. The L+dBcAMP mice had significantly short entry latency and higher target quadrant time/distance traveled compared to the L+PBS group, suggesting better memory retention. The L+dBcAMP group had a significantly improved memory retention compared to the L+PBS mice during the passive avoidance test. Morphological studies showed significantly greater adult neurons and increased hippocampal neurogenesis in the hippocampus of mice in the L+dBcAMP group compared to those in the L+PBS group. There was no significant difference between the S+dBcAMP and S+PBS groups in the water maze/passive avoidance tests and the number of neurons. In conclusion, dBcAMP protects the hippocampal neuron from degeneration and enhances hippocampal neurogenesis, learning, and memory.

Research Progress Evaluating the Function and Mechanism of Anti-Tumor Peptides.

Malignant tumors cause a high mortality rate worldwide, and they severely threaten human health and negatively affect the economy. Despite the advancements in tumor-related molecular genetics and effective new processes in anti-tumor drug development, the anti-tumor drugs currently used in clinical practice are inadequate due to their poor efficacy or severe side effects. Therefore, developing new safe and efficient drugs is a top priority for curing cancer. The peptide has become a suitable agent due to its exact molecular weight between whole protein and small molecule, and it has high targeting ability, high penetrability, low immunogenicity, and is convenient to synthesize and easy to modify. Because of these advantages, peptides have excellent prospect for application as anti-tumor agents. This article reviews the recent research progress evaluating anti-tumor peptides and their anti-tumor mechanisms, and may act as a reference for the future development and clinical application of anti-tumor peptides.

Comprehensive Evaluation of Gene Expression in Negative and Positive Trigger-based Targeting Niosomes in HEK-293 Cell Line.

An efficient gene delivery system has some critical factors that enhance the efficiency of nanocarrier. These factors are low production cost, high bioavailability, high encapsulation efficiency, controllable release, and targeting ability. Niosome (the nonionic surfactant vesicles) was considered as a promising gene delivery system. Niosome can increase stability and uptake of active agents. We used all mentioned factors in one optimized formulation entitled plasmid- loaded magnetic niosomes (PMN). To increase the bioavailability of niosomes, we used ergosterol (a natural lipid) instead of cholesterol in structure of niosome. Also, cetyl trimethyl ammonium bromide (CTAB) in different concentrations was used to improve encapsulation of plasmid and compared to niosomes that did not have CTAB (negative niosome). Afterward, magnetic nanoparticle (Fe3O4@SiO2) was synthesized and loaded into niosome to obtain targeting ability. Prepared formulations were evaluated regarding size, zeta potential, morphology, encapsulation of magnetic nanoparticles and plasmid (Pm-cherry-N1), release rate, and transfection efficiency. Results demonstrated that optimum formulation (Nio/CTAB3%/Fe/P) has a nanometric size (118 ± 2.31 nm, positive zeta potential (+25 ± 0.67 mV), high loading of plasmid (72%), and good gene expression (35%). Interestingly, after applying a magnetic field below the cell plate, we obtained ac increased gene expression from 35% to 42%. These results showed that this new formulation would have a promising future and also can be used for delivering the other drugs and active agents.

Heat Loss Characteristics of Pipe Flange Joints: Experiments and Simulations

Abstract Sealing performance and heat loss are important factors for pipe flange joints (PFJs) subjected to medium or high temperatures. Heat loss is of great interest in practical engineering for uninsulated PFJs. Since an insulation layer may degrade the sealing performance of PFJs, heat loss of PFJs was tested and simulated considering various ambient temperatures of −10 °C, 0 °C, 10 °C, 20 °C, 30 °C, and 40 °C, with wind speeds of 0 m/s and 3 m/s and flange joint target temperatures of 200 °C, 300 °C, and 400 °C. It is worth noting that the experiments were performed during summer for high ambient temperatures and during winter for low ambient temperatures. As expected, the steady temperature slightly increases with the increase of external ambient temperature. For the same flange joint temperature, a 3 m/s wind speed decreases significantly the steady temperature, especially when the higher target temperature is applied. If the external wind speed is 3 m/s and the flange joint target temperatures are 200 °C, 300 °C, and 400 °C, respectively, the heat loss increases by approximately 38.4%, 30.7% and 23.6% when the ambient temperature changes from 30 °C to 10 °C. Moreover, the simulated temperatures agree well with the tested temperatures in most cases, and the average error is approximately 8%. The energy saving efficiency under the windless condition is approximately on average 26% higher than that with a wind speed of 3 m/s.

Cloning and expression of Helicobacter pylori Neutrophil-activating protein fused to the 6xHis tag in Escherichia coli

Helicobacter pylori (Hp) has been strongly implicated as a causative factor in peptic ulcer disease, and in significantly increasing the risk of developing gastric cancer. Commercial vaccines nowadays have shown less efficiency on preventing the disease caused by Hp. Therefore, this study was performed to clone nap gene from Hp and over-express the encoded protein (NAP) in E. coli cells. NAP (Neutrophil-activating protein) has been considered as a potential antigen of Hp, can be used to produce peptic ulcer prevention vaccine. The obtained results showed that E. coli OmniMAX and E. coli BL21 (DE3) strains carrying recombinant plasmid pET11a-nap were cloned successfully and remained stable in medium supplemented with ampicillin. Over-expression of NAP protein fused with 6xHis in E. coli was demonstrated via SDS-PAGE and Western blot. The result revealed that the highest target protein production level (29.73%) was obtained in the medium added 0.5 mM IPTG at 37 oC after 6 hours of induction. This is the preliminary research for over-production and purification of Hp-NAP protein that may be used in further applications.

Improving the Students’ Speaking Skill through Debate Technique

AbstractSpeaking is the highest target in English language because speaking is basis of communication which becomes a function learning. There are many kinds of technique to improve speaking skill and one of them is debate Technique. Therefore, the researcher wanted to find out whether or not debate technique can improve the students’ speaking skill and to analyze the classroom situation when debate technique is implemented in speaking class. This research used Collaborative Classroom Action Research and composed for two cycle then it practical and evaluated to categorize all facts including the success and the failure of the action. It means that the action should be stopped or continued and revised to the next cycle based on the selected criteria of success.The application of debate technique in teaching speaking at the first year of SMK Fajar Kencana was accompanied in two cycles including cycle one and cycle two. The members of this study were 29 students in class X AP. This is confirmed by students’ test score that upgraded in every cycle. In the cycle 1, the students’ got score of pre-test was 64,28. After the implementation of , the students’ speaking score were getting better.It can be seen from the result of students’avarage score cycle 1 was 67 and cycle 2 was 78.5. Debate is an appropriate technique used to improve students’ speaking skill for the students at SMK Fajar Kencana class X AP. It can be concluded that debate technique can improve students’ speaking interest and debate technique can improve speaking classroom into a better situation.

Redox/NIR dual-responsive MoS2 for synergetic chemo-photothermal therapy of cancer

BackgroundThe construction of a multifunctional drug delivery system with a variety of advantageous features, including targeted delivery, controlled release and combined therapy, is highly attractive but remains a challenge.ResultsIn this study, we developed a MoS2-based hyaluronic acid (HA)-functionalized nanoplatform capable of achieving targeted delivery of camptothecin (CPT) and dual-stimuli-responsive drug release. HA was connected to MoS2 via a disulfide linkage, forming a sheddable HA shell on the surface of MoS2. This unique design not only effectively prevented the encapsulated CPT from randomly leaking during blood circulation but also significantly accelerated the drug release in response to tumor-associated glutathione (GSH). Moreover, the MoS2-based generated heat upon near-infrared (NIR) irradiation could further increase the drug release rate as well as induce photothermal ablation of cancer cells. The results of in vitro and in vivo experiments revealed that MoS2–SS–HA–CPT effectively suppressed cell proliferation and inhibited tumor growth in lung cancer cell-bearing mice under NIR irradiation via synergetic chemo-photothermal therapy.ConclusionsThe as-prepared MoS2–SS–HA–CPT with high targeting ability, dual-stimuli-responsive drug release, and synergistic chemo-photothermal therapy may provide a new strategy for cancer therapy.

Abstract 344: SJP1604, a novel targeted therapeutic agent for AML (acute myeloid leukemia) including standard therapy-resistant AML

Abstract Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are cancers characterized by the rapid growth of abnormal white blood cells. Generally, cytarabine (Ara-C), azacitidine, and decitabine are treated as the standard first-line chemotherapy for AML/MDS. Although the therapy leads to high rates of remission, approximately 30% of the treated patients are refractory and more than 50% of them face a relapse because of the occurrence of drug resistance and high toxicity. Therefore, there is a strong unmet need for the next-generation targeted therapy to overcome drug resistance and reduce toxicity in AML/MDS. Here, we designed an aptamer-nucleoside drug conjugate (SJP1604) via utilizing easy and continuous synthesis specific for nucleolin, which is highly expressed only on the cell membrane of cancer cells. In particular, AML, CLL (chronic lymphoblastic leukemia) and ALL (acute lymphoblastic leukemia) cells are known to express the highest mRNA level of nucleolin among various cancer cells, relatively. SJP1604 can be delivered into cancer cells with its high targeting ability and plasma stability via its unique conformational property. In this study, we verified that SJP1604 selectively targeted cancer cells by nucleolin-binding on the cancer cell membrane in the drug uptake assay. Owing to the selectivity, SJP1604 demonstrated less cytotoxicity on murine bone marrow cells in vitro and mouse white blood cells in vivo. SJP1604 also exhibited a long-lasting plasma stability in 50% human plasma up to 48 hours in contrast to unstability of general aptamers. Furthermore, SJP1604 inhibited the growth of various human AML/MDS cancer cells. Interestingly, SJP1604 showed the significantly reduced IC50 values with the decreased expression level of nucleolin in cytarabine-, azacitidine- and decitabine-resistant MOLM-13 while cytarabine caused no effect on the cell growth and the expression of nucleolin of the same resistant cell lines. Injection of SJP1604 led to tumor regression and improved survival rate in MOLM-13 xenograft mouse model and C1498 syngeneic mouse model. In ex vivo study, we figured out that the expression level of nucleolin is highly up-regulated in AML patient-derived bone marrow cells and the level is much higher in relapsed/refractory (R/R) AML patient-derived bone marrow cells. Moreover, SJP1604 also significantly reduced the colony forming unit (CFU) of R/R AML patient-derived bone marrow cells compared to that of AS1411 treatment. In conclusion, these findings suggest that SJP1604 could be developed as a first-in-class drug for novel targeted therapy of AML/MDS with less drug toxicity as well as as a remarkable orphan drug for overcoming drug resistance of AML/MDS in which distinctive solutions do not exist up until recently. Citation Format: Jihyun Um, Dohyeong Lee, Jisun Oh, Yongbin Park, Sung Hwan Moon, Su Jin Lee, Min-Hyo Ki, Eui Hwan Cho. SJP1604, a novel targeted therapeutic agent for AML (acute myeloid leukemia) including standard therapy-resistant AML [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 344.

Coarse Woody Debris Management with Ambiguous Chance Constrained Robust Optimization

Coarse woody debris (deadwood) serves as a dwelling space for many rare species, and is therefore a most important factor to ensure diversity in forest ecosystems. However, wood from forest ecosystems is also needed for construction and heating. Therefore, a forest enterprise has to simultaneously incorporate the provision of suitable habitats, as well as the production of wood into their long-term management plans. If the owner wants to fulfil such multiple objectives in an effective way, the providing of ecosystem services can be included in economic planning. Applying computer aided robust optimization techniques, we optimized the provision of deadwood for two exemplary enterprises in East Bavaria, Germany. The results show that high amounts of deadwood provision can cause severe opportunity costs for the forest owner. These costs highly depend on the tree species, the sorting strategy and the time horizon, in which the deadwood objective is reached. Low deadwood targets up to 5 m 3 h a − 1 can be provided most cost-effectively with crown material, while higher targets (20 m 3 h a − 1 and more) are better achieved with heavy timber grades or the provision of total trees. The novelty of our research is the inclusion of deadwood targets in a risk-considering optimization tool on enterprise level. Instead of calculating the economic loss of commercially not-used timber assortments we show a way of deriving the impact of such decisions at stand level on the economic performance of the whole forest enterprise. We were able to derive optimized opportunity costs. These costs can be used as guidelines for necessary incentives to encourage forest owners to incorporate the provision of deadwood into their management.

199-LB: Low Prevalence of Small-for-Gestational-Age in Women with Type 1 Diabetes and Chronic Hypertension

Objective: To evaluate delivery outcomes in women with concurrent type 1 diabetes and chronic hypertension (cHTN) treated with anti-hypertensive pharmacotherapy to target blood pressure (BP) 110-129/65-79 mmHg throughout pregnancy per ADA 2008-2016 guidelines. Research Design and Methods: We abstracted clinical data from the medical records of 752 pregnancies derived from 550 women seeking prenatal care at the Joslin Diabetes Center and Beth Israel Deaconess Medical Center’s Diabetes in Pregnancy Program from 2004-2017. We calculated means and percentages, used t test or ?2 test, and linear regression to compare trimester specific BP values, birth weight and prevalence of small for gestational age (SGA) in pregnancies of women with type 1 diabetes and cHTN to those with type 1 diabetes and no cHTN. Results: Type 1 diabetes and cHTN occurred in 51 (6.7%) of pregnancies and the mean BP values were 128/76 in the first trimester; 122/72 in the second trimester; 124/76 in the third trimester; 137/82 prior to delivery. BP values were significantly higher in women with type 1 diabetes and cHTN for each trimester compared to women with type 1 diabetes and no cHTN (p<0.001). Women with type 1 diabetes and cHTN were older (33.4 vs. 31.5 years p=0.04), had higher BMI (28.3 vs. 26.6 kg/m2 p=0.03), were more likely to have diabetic nephropathy (10.4% vs. 2%, p<0.001) and use insulin pumps (75.5% vs. 60%, p=0.04). There were no significant differences in gestational age at delivery and birth weight. SGA in both groups was rare, with 0 (0%) in the type 1 diabetes with cHTN group and 5 (0.9%) in the group without cHTN (p=0.54). Conclusion: SGA is rare in pregnancies complicated by type 1 diabetes and cHTN and did not differ from those without cHTN, even when BP targets of 110-129/65-79 mmHg are used. This may provide reassurance to reestablish these lower BP targets rather than the recently adopted higher targets of 120-160/80-105 mmHg followed by ACOG since 2013 and ADA since 2017. Disclosure S. Helman: None. T. James-Todd: None. F.M. Brown: None.

Effect of oxygen saturation targets on the incidence of bronchopulmonary dysplasia and duration of respiratory supports in extremely preterm infants.

Recent clinical practice changes in neonatal care resulted in higher, narrower oxygen saturation target ranges for preterm infants. The effect of targeting higher or lower oxygen saturations on respiratory outcomes of preterm infants and duration of hospitalization has not been extensively reviewed in the context of current care, but could have significant implications. A multicentre retrospective cohort of 145 preterm infants was conducted; 105 had lower oxygen saturation targets (88 to 92%), 40 had higher targets (90 to 95%). The primary outcome was bronchopulmonary dysplasia (BPD). Secondary outcomes included duration of invasive/noninvasive respiratory support, oxygen therapy, and hospitalization. The primary outcome was compared using Fisher's exact test. Secondary outcomes were evaluated with survival analysis and Wilcoxon rank sum test. The difference in incidence of BPD in the lower (N=56, 53.3%) and higher saturation groups (N=14, 35.0%) was not statistically significant (relative risk [RR]=0.66 [0.41, 1.04], P=0.06). The difference in duration of mechanical ventilation in the lower (median 7.8 days, interquartile range [IQR] 3.7 to 15.9) and higher saturation groups (median 4.5, IQR 1.9 to 12.3) approached statistical significance (P=0.05). There were no statistically significant differences in the durations of other respiratory supports or hospital stay between the two groups. The results of this study approached statistical significance and suggest that higher, narrower oxygen saturation targets may result in a clinically important reduction in BPD incidence and duration of mechanical ventilation. These results require validation in a larger sample to refine optimal targets.

Quantification and Imaging of Antigens on Cell Surface with Lipid-Encapsulated Fluorescent Nanodiamonds

Quantifying the density and locating the position of antigens on cell surface has been a challenge in molecular biology research. The challenge lies in the need for a chemically and photophysically stable fluorophore to achieve the required sensitivity and accuracy. Here, we present a method suitable for the purpose by using lipid-encapsulated fluorescent nanodiamonds (FNDs) of 35 nm in diameter as biolabels. The encapsulation of FNDs in biotinylated phospholipids not only facilitates good dispersion of the particles in biological buffers, but also endows them with high specific targeting ability. We demonstrated a viable application of the technique for biotin-mediated immunostaining of antigens on fixed human cells, identifying their positions by two-color confocal fluorescence imaging, and determining their densities by magnetically modulated fluorescence detection. A binding capacity of 6 ± 1 × 104 antigens/cell was measured specifically for CD44 on HeLa cell surface. The result agreed well with the assay of R-phycoerythrin-conjugated antibodies by flow cytometry, supporting the reliability of this new nanoparticle-based method.

ANALISIS KEPATUHAN WAJIB PAJAK BADAN BERDASARKAN REALISASI PENERIMAAN PAJAK PENGHASILAN PADA KANTOR PELAYANAN PAJAK (KPP) PRATAMA CILEGON

This study aims to examine the Analysis of Compliance with Corporate Taxpayers Based on Realization of Income Tax Receipts at Pratama Tax Service Office (KPP) Cilegon. The research method used in this research is descriptive analysis. With this method, the research data is compiled, interpreted, described and analyzed. The type of data used in this study uses qualitative data, data obtained from KPP Pratama Cilegon from 2014-2017. The results of this study conclude that when viewed from 2014-2017 the number of corporate taxpayers increases every year. The increase in the number of corporate taxpayers above shows that the potential for corporate income tax revenues will increase every year. Target and acceptance of corporate income tax increase. In 2014-2015 tax receipts reached the target set. It's just that in 2016-2017 with a higher target, the realization of corporate income tax revenue does not reach the specified target. Efforts made to optimize income tax receipts at Pratama Tax Service Office (KPP) Cilegon are to carry out socialization, drop box, and pick up the ball.

Synthesis and characterization of aminolevulinic acid with gold and iron nanoparticles by photoreduction method for non-communicable diseases diagnosis and therapy

Non-communicable diseases (NCDs) are a group of chronic diseases resulted by genetic, epigenetic and environmental factors and life style. The main types of NCDs are cardiovascular diseases and cancers. Some of therapeutic treatments for NCDs induce severe cytotoxicity to normal cells. New treatments as photodynamic and sonodynamic therapies have been proposed trying to improve the cure rate and reduce the side-effects. In these treatments certain drugs as porphyrins precursors associated to metal nanoparticles (MNPs) have become of extreme interest since have high targeting ability and potentiality to destroy tumor tissues. MNPs can induce cell death through various processes, including reactive oxygen species (ROS) generation and DNA damage, among others. In this work, we describe synthesis of MNPs by photoreduction with aminolevulinic acid (ALA), a protoporphyrin IX precursor. To obtain ALA:MNPs (M = Au or/and Fe), ALA, polyethylene glycol, and Tetrachloroauric acid and/or iron powder water solutions were irradiated by Xenon lamp. The UV–vis spectra, transmission electron microscopy and zeta potential were measured to characterize nanoparticles. The proposed mechanism of nanoparticle formation was described from a physicochemical perspective. The THP-1 macrophages cytotoxicity was determined, and photodynamic therapy (PDT) with high power LED at 590 nm for 2 min were performed. The results have suggested that the gold/iron nanoparticles interfere in the selectivity of iron transport across the mitochondrial inner membrane and enhance the effectiveness of the PDT acting as important agent for NCDs control.

Is the Modernization Process Becoming a Challenge or a Threat to the Security Policy and the Armed Forces?

In spite of defining the role of various measures of security policy implementation the weight of one has been quite unequivocally assessed for the current policy. The main position for contemporary Poland is to be taken by the armed forces. Under these conditions, the Polish Army has become a basic element of the defense system of Poland not only in terms of image. It is not surprising then that currently the armed forces have received a wide range of tasks regarding security – both internal and external. President Duda and the government of Law and Justice proudly show the 2 percent of GDP spent on defense and an even higher target, at the latest in 2030. However, this does not create a perspective that would allow “hurray” optimism. The key to describing the Armed Forces of the Republic of Poland seems to be their ability to respond to the revolution in the field of military and the ability to modernize. Despite the plans of the Ministry of National Defense and declarations given in media, this process faces a number of difficulties. Not only do we create “abstract” visions of needs for the current policy, but we also offend our partners and those that are still our allies. The arms policy, so important from the point of view of this “self-sufficiency”, was brought to the accusations of lobbying, corruption, and fraud; not only do we not pay attention to our own needs, but we also create innovative concepts for the current policy that cause us to wander in dilettantism. It seems that the shape of the implementation of the modernization of the Armed Forces is affected not only by the current policy. To a large extent, the condition of the Polish arms industry is also a decisive factor in the absorption of modernization.