Extremely low warfarin dose in patients with genotypes of CYP2C9*3/*3 and VKORC1-1639A/A

Background  Patients with the genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A are expected to require the lowest dose of warfarin, and to have a greatly increased risk of bleeding. The experience for the dosing of warfarin in such extremely rare cases has been seldom reported.

Methods  Demographic and clinical data from two cases with stable low dose of warfarin in China were studied by resequencing the corresponding gene segments in their whole blood DNA. The potential clinical value of the pharmacogenetic algorithm for them was evaluated by calculating the stable dose of warfarin in pharmacogenetic algorithm developed by International Warfarin Pharmacogenetics Consortium. 

Results  Both cases (68-year-old female and 50-year-old male) were diagnosed as chronic nonvalvular atrial fibrillation needing warfarin treatment, with target international normalized ratio (INR) 2 to 3. Case 1 had stable warfarin dose of 0.625 mg/d and case 2 1.25 mg/d. They needed more than 1 month to stabilize their anticoagulation. Exceeding INR values were recorded for them when the dose of warfarin was no more than 2 mg/d. Hemorrhagic complication appeared in case 1 when the dose was titrated from 2.5 to 1.25 mg/d. No concomitant medicine to increase or decrease the INR value was recorded for them. Genotyping CYP2C9 and VKORC1 showed both patients were the carriers of the homozygous alleles–CYP2C9*3/*3 and VKORC1-1639 A/A. Their stable doses of warfarin calculated by the pharmacogenetic dose algorithm (0.672 mg/d for case 1 and 1.16 mg/d for case 2) were comparable with their actual stable therapeutic doses. 

Conclusions  Two Chinese with the rare genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A were found to require the extremely low dose of warfarin. The pharmacogenetic algorithm incorporating the variances of VKORC1 and CYP2C9 genotypes, as well as the non-genetic factors could predict their stable dose of warfarin with high accuracy.

     

Factors affecting warfarin dose requirements and quality of anticoagulation in adult Egyptian patients: role of gene polymorphism

Background

Warfarin is the mainstay of anticoagulation therapy worldwide. CYP2C9 and VKORC1 are two major genetic factors associated with inter-individual and inter-ethnic variability in the warfarin dose.

Aim

This study aims to assess the impact of VKORC1–1639G>A polymorphism and the most common CYP2C9 variant alleles (*2 and *3) on warfarin response in Egyptian patients.

Methods

Genetic analysis of VKORC1–1639G>A and CYP2C9*2, CYP2C9*3 was performed using real-time PCR system. Patients maintained on a constant dose targeting an international normalized ratio range of 2–3.5 for at least three consecutive times were considered as good candidates. A stepwise linear regression analysis was used to determine the independent effects of genetic and non-genetic factors on daily warfarin dose requirements.

Results

Patients carrying VKORC1 and CYP2C9 variant genotypes needed a 44.8 % lower mean daily warfarin dose as compared to wild types. Patients with G allele for VKORC1–1639G>A had a significantly higher number of thromboembolic complications per month during therapy. On the first 30 days of therapy, presence of a variant allele either in VKORC1 or in CYP2C9 was associated with increased time required to achieve stable dosing. Multiple regression analysis showed that, VKORC1–1639G>A, age, CYP2C9*3, and smoking status explained 43.4 % of the overall variability in the warfarin dose.

Conclusion

VKORC1–1639G>A and CYP2C9 polymorphisms contribute to the difference in warfarin dose requirements and quality of anticoagulation amongst Egyptian patients. Study results support using personalized warfarin treatment in Egyptian patients.     

高原人群CYP2C9和VKORC1基因多态性及其与华法林用药剂量的相关性研究

目的 探讨高原人群基于中国人群华法林用药剂量计算公式（PRC模型）和国际华法林遗传药理学协会推荐的亚裔人群华法林剂量计算公式（IWPC模型）两种模型预测剂量的准确性及其临床应用价值。方法 回顾性分析曲靖市第一人民医院2016年10月—2020年1月375例行华法林代谢基因多态性检测患者的临床资料。通过qRT-PCR检测CYP2C9和VKORC1基因多态性,记录患者基本信息和临床用药情况,采用两种模型计算预测剂量并分析其与维持剂量［国际标准化比值（INR）稳定维持在2.0～3.0范围内时所服用的华法林剂量］的相关性,评估两模型预测的准确性。结果 在实际治疗过程中患者是否选择服用华法林进行抗凝,通常与患者的性别、身高、吸烟史、是否合并房颤、是否注射低分子肝素钙无关,而与患者年龄、体重、体表面积（BSA）、初INR、是否置换主动脉瓣膜、是否服用阿司匹林、利伐沙班或氯吡格雷相关。375例患者CYP2C9和VKORC1基因频率符合Hardy-Weinberg遗传平衡定律,其中CYP2C9基因*1/*1（AA）、*1/*3（AC）及*3/*3（CC）基因型频率分别为93.07%（349/375）、6.93%（26/375）和0.00%（0/375）,VKORC1-1639基因AA、AG和GG基因型频率分别为82.66%（310/375）、16.27%（61/375）和1.07%（4/375）。无论是使用PRC还是IWPC模型,除CYP2C9*1/*1 & VKORC1AA（n =289）组与CYP2C9*1/*3 & VKORC1AG（n =5）组预测剂量的差异无统计学意义（P >0.05）外,其他所有基因型组预测剂量两两比较均有差异（P <0.05）。在收集到维持剂量的174例患者中,CYP2C9*1/*1 & VKORC1 AG和CYP2C9*1/*1 & VKORC1 GG组维持剂量分别为［（3.41±1.01）mg,n =30］和［（4.75±0.35）mg,n =2］,均高于CYP2C9*1/*1 & VKORC1 AA组［（2.59±0.73）mg,n =136］（P <0.05）;CYP2C9*1/*3 & VKORC1 AA组维持剂量为［（2.00±0.53）mg,n =5］,低于其他基因型组合（P <0.05）。PRC和IWPC模型预测准确性分别为72.99%（127/174）和62.64%（109/174）;Pearson相关系数（r₁ =0.546,r₂ =0.567）;决定系数（R₁²=0.298,R₂²=0.322）。两个模型预测剂量间无差异（r =0.839,P >0.05）。结论 携带CYP2C9*3等位基因的患者对华法林更敏感,所需华法林剂量较低,而携带VKORC1-1639 G等位基因的患者需要更高剂量的华法林才可以获得有效的抗凝疗效。基因组学预测剂量可为临床使用华法林剂量提供依据,提高抗凝治疗的安全性和有效性。     

Pharmacognostical,phytochemical and pharmacological evaluation for the antipyretic effect of the seeds of Saraca asoca Roxb.

Objective

To conduct a systemic evaluation of the medicinal value of seeds which include macroscopic and microscopic characterization, physiochemical evaluation, preliminary phytochemical screening and experimental antipyretic activity.

Methods

Saraca asoca seed was studied for pharmacognostical, phytochemical and other recommended methods for standardizations. Also, the acetone extract of the seeds was evaluated for acute toxicity study and antipyretic activity using Brewer''s yeast induced pyrexia in Wistar rats at oral doses of 300 mg/kg and 500 mg/kg.

Results

After phytochemical screening, the acetone extract showed the presence of saponin, tannins and flavonoids which inhibit pyrexia. The therapeutic efficacy achieved at both the dose levels of the research drug and standard drug aspirin (100 mg/kg) showed significant (P<0.01) antipyretic activity when compared to the control group. The highly significant antipyretic effect exhibited at the dose of 500 mg/kg was also found to be sustainable in nature.

Conclusions

The antipyretic effect of the acetone extract showed significant results in rats at the dose of 500 mg/kg after following the standard pharmacognostical and phytochemical methods.     

Characteristics and effects of nurse dosing over-rides on computer-based intensive insulin therapy protocol performance

Objective

To determine characteristics and effects of nurse dosing over-rides of a clinical decision support system (CDSS) for intensive insulin therapy (IIT) in critical care units.

Design

Retrospective analysis of patient database records and ethnographic study of nurses using IIT CDSS.

Measurements

The authors determined the frequency, direction—greater than recommended (GTR) and less than recommended (LTR)— and magnitude of over-rides, and then compared recommended and over-ride doses'' blood glucose (BG) variability and insulin resistance, two measures of IIT CDSS associated with mortality. The authors hypothesized that rates of hypoglycemia and hyperglycemia would be greater for recommended than over-ride doses. Finally, the authors observed and interviewed nurse users.

Results

5.1% (9075) of 179 452 IIT CDSS doses were over-rides. 83.4% of over-ride doses were LTR, and 45.5% of these were ≥50% lower than recommended. In contrast, 78.9% of GTR doses were ≤25% higher than recommended. When recommended doses were administered, the rate of hypoglycemia was higher than the rate for GTR (p=0.257) and LTR (p=0.033) doses. When recommended doses were administered, the rate of hyperglycemia was lower than the rate for GTR (p=0.003) and LTR (p<0.001) doses. Estimates of patients'' insulin requirements were higher for LTR doses than recommended and GTR doses. Nurses reported trusting IIT CDSS overall but appeared concerned about recommendations when administering LTR doses.

Conclusion

When over-riding IIT CDSS recommendations, nurses overwhelmingly administered LTR doses, which emphasized prevention of hypoglycemia but interfered with hyperglycemia control, especially when BG was >150 mg/dl. Nurses appeared to consider the amount of a recommended insulin dose, not a patient''s trend of insulin resistance, when administering LTR doses overall. Over-rides affected IIT CDSS protocol performance.     

Towards spoken clinical-question answering: evaluating and adapting automatic speech-recognition systems for spoken clinical questions

Objective

To evaluate existing automatic speech-recognition (ASR) systems to measure their performance in interpreting spoken clinical questions and to adapt one ASR system to improve its performance on this task.

Design and measurements

The authors evaluated two well-known ASR systems on spoken clinical questions: Nuance Dragon (both generic and medical versions: Nuance Gen and Nuance Med) and the SRI Decipher (the generic version SRI Gen). The authors also explored language model adaptation using more than 4000 clinical questions to improve the SRI system''s performance, and profile training to improve the performance of the Nuance Med system. The authors reported the results with the NIST standard word error rate (WER) and further analyzed error patterns at the semantic level.

Results

Nuance Gen and Med systems resulted in a WER of 68.1% and 67.4% respectively. The SRI Gen system performed better, attaining a WER of 41.5%. After domain adaptation with a language model, the performance of the SRI system improved 36% to a final WER of 26.7%.

Conclusion

Without modification, two well-known ASR systems do not perform well in interpreting spoken clinical questions. With a simple domain adaptation, one of the ASR systems improved significantly on the clinical question task, indicating the importance of developing domain/genre-specific ASR systems.     

Antiarthritic effects of Ajuga bracteosa Wall ex Benth. in acute and chronic models of arthritis in albino rats

Objective

To evaluate the antiarthritic activity of Ajuga bracteosa using albino rats.

Methods

The antiarthritic activity of 70% ethanolic extract of Ajuga bracteosa (EEAB) was evaluated against turpentine oil- and formaldehyde- induced acute non immunological and complete freund''s adjuvant (CFA)-induced chronic immunological arthritis in albino rats.

Results

EEAB showed a significant (P<0.05) and dose dependent inhibitory effect against acute and chronic models of arthritis. EEAB exhibited better antiarthritic activity than the standard aspirin.

Conclusions

EEAB exhibits a significant and promising antiarthritic activity against acute and chronic arthritis and supports the traditional use of Ajuga bracteosa for rheumatism and other inflammatory diseases.     

Pharmacognostic study and anti-inflammatory activity of Callistemon lanceolatus leaf

Objective

To study detail pharmacognosy and anti-inflammatory activity of Callistemon lanceolatus (C. lanceolatus) leaf.

Methods

Leaf sample was studied by organoleptic, macroscopical, microscopical, phytochemical and other WHO recommended methods for standardizations. The methanolic leaf extract of the plant was also screened for anti-inflammatory activity on carrageenan-induced paw edema in rat at doses of 200 and 400 mg/kg, orally. The detail pharmacognostic study of the C. lanceolatus leaf was carried out to lay down the standards which could be useful in future experimental studies.

Results

C. lanceolatus methanolic leaf extract showed significant (P<0.05) anti-inflammatory activity at doses of 200 mg/kg and 400 mg/kg. This significant anti-inflammatory of C. lanceolatus methanolic leaf extract at the dose of 400 mg/kg was comparable with diclofenac sodium.

Conclusions

The pharmacognostic profile of the C. lanceolatus leaf is helpful in standardization for quality, purity and sample identification. The methanolic extract at a dose of 400 mg/kg shows a significant activity in comparison with the standard drug diclofenac sodium (50 mg/kg).     

CYP2C18基因多态性对瓣膜置换术后服用华法林剂量的影响研究

目的 探讨云贵高原汉族人群细胞色素P450 (CYP) 2C18、维生素K环氧化物还原酶复合体亚单位1(VKORC1)、CYP2C9的基因型分布情况及其基因多态性与华法林稳定剂量的相关性.方法 以2011年1月至2014年1月在该院行瓣膜置换术后持续服用华法林抗凝治疗的云贵高原汉族患者176例为研究对象,采集静脉血检测各位点基因型,分析基因型及等位基因频率分布,以及基因多态性与华法林稳定剂量的相关性.结果 各位点基因型及等位基因频率分布均符合Hardy-Winberg遗传平衡(P＞0.05);CYP2C18(rs7896133)、VKORC1 (rs9923231)、CYP2C9(rs1057910)、CYP2C9 (rs4086116)基因位点的基因多态性与华法林稳定剂量相关(P＜0.05).结论 云贵高原汉族患者CYP2C18(rs7896133)、VKORC1(rs9923231)、CYP2C9(rs1057910)、CYP2C9(rs4086116)基因多态性可能是华法林稳定剂量个体差异的影响因素.     

Anti-inflammatory,analgesic and antipyretic activity of methanolic Tecomaria capensis leaves extract

Objective

To evaluate the analgesic, anti-inflammatory and antipyretic activity of methanolic Tecomaria capensis (T. capensis) leaves extract using different models in rats.

Methods

Methanolic T. capensis leaves extract (100, 300, 1000 and 2000 mg/kg body weight) was given to rats orally to observe acute toxicity, and observed for 14 days. Analgesic activity was evaluated using tail immersion and formalin induced paw licking models in rats. Anti-inflammatory activity was evaluated using carrageenan induced paw edema model in rats. Antipyretic activity was evaluated using brewer''s yeast induced pyrexia model in rats. Methanolic T. capensis leaves extract were given at dose of 100, 200 and 500 mg/kg p.o.

Results

Results demonstrated that the no mortality was reported even after 14 days. This indicated that the methanol extract was safe up to a single dose of 2 000 mg/kg body weight. Methanolic T. capensis leaves extract (100, 200 and 500 mg/kg p.o.) significantly increased the latency period in the tail immersion test, reduced the licking time in both the neurogenic and inflammatory phases in the formalin test. Methanolic T. capensis leaves extract (100, 200 and 500 mg/kg p.o.) significantly prevented increase in volume of paw edema. Methanolic T. capensis leaves extract at the doses of (100, 200 and 500 mg/kg p.o.) significantly decreased the rectal temperature of the rats.

Conclusions

This study exhibites that methanolic T. capensis leaves extract possesses analgesic, anti-inflammatory and antipyretic activity which may be mediated by the central and peripheral mechanisms.     

瓣膜置换术后华法林稳定剂量预测模型研究

目的:研究瓣膜置换术后CYP2C9*2、CYP2C9*3、CYP4F2、GGCX、VKORC1-1173、VKORC1-1639基因多态性,及人口学、临床因素对瓣膜置换术后华法林稳定剂量的影响,建立华法林稳定剂量的预测模型。方法:收集226例瓣膜置换患者,提取DNA,设计引物,应用聚合酶链式反应（PCR）技术扩增上述位点基因,应用酶切技术,以特定内切酶切出相关基因,以电泳显示最终结果,得出目标DNA基因序列,回顾追踪患者服药剂量、临床资料、人口学特征,并长期监测其INR,结合有无出血、血栓形成,得出瓣膜置换术后华法林稳定剂量预测模型。结果:得出华法林稳定剂量预测模型:Y=2.131-1.816VKORC1-1173+0.369GGCX+1.529BSA-0.013Age(V1173当基因型为AA型时,取1,非AA型取0,当GGCX为GT型时取1,非GT型取0,BSA单位为㎡,Age单位为岁)。华法林稳定剂量与体表面积、年龄、VKORC1-1173、GGCX基因型相关,与CYP2C9*2、CYP2C9*3、CYP4F2、VKORC1-1639无明显线性关系。结论: VKORC1-1173的AA基因型与年龄与华法林稳定剂量呈负相关,而GGCX的GT基因型与体表面积与华法林稳定剂量呈正相关。     

Effect of insulin on Blattela germanica Linnacus

Objective

To determine the sensitivity of Blattela germanica L (B. germanica L) to differenct doses of insulin.

Methods

B. germanica were reared in laboratory conditions at (25±2) °C and (50±5)% relative humidity (RH), and exposure period of 12:12 L/D. Different concentrations, viz. 5, 10, 15, 20 and 25 µ of insulin N, R, (N+R) were prepared and injected to 10 treated cockroaches with another 10 cockroaches which were injected with normal saline as control group.

Results

Insulin N with a dose of 20 µ caused more than 70% mortality of B. germanica in this study. There was a significant difference between 20 µ of insulin N with other doses of 5, 10, 15 and 25 µ, and its comparison with other forms of medication also showed obvious difference (P<0.05).

Conclusions

It can be concluded that effective drug doses of insulin which can be used as posion bait or gel against German cockroaches could be utilized in the control of B. germanica in the future field studies.     

Assessment of antidiabetic activity and acute toxicity of leaf extracts from Physalis peruviana L. in guinea-pig

Objective

To verify the antidiabetic activity of leaf extracts from Physalis peruviana L. popularly used in the Eastern part of the Democratic Republic of the Congo and to point out the possible toxicity.

Method

Aqueous decoctions prepared from dried leaves powder were administrated to guinea pigs at the dose range of 100 mg/kg to 3.2 g/kg of body weight. The hypoglycemic activity was evaluated by glucose tolerance test, loading animals with glucose 4 g/kg and measuring blood glucose concentrations at various times. The effect was compared to the control and glibenclamide as antidiabetic reference drug. Acute toxicity was evaluated by recording mortality rate, changes on blood biomarkers and damage caused to vital organs.

Results

At a dose of 100 mg/kg, the aqueous extract induced a significant reduction of peak concentration at 30 min after glucose loading as compared with control or reference (P<0.05). At doses greater than 400 mg, some alterations on blood, kidney and liver markers were observed. Upper 800 mg/kg, mortality was observed with LD₅₀ estimated at about 1 280 mg/kg. At the autopsy, vital organs were in haemorrhage and swelling state.

Conclusion

The crude aqueous extracts from the leaves of Physalis peruviana L. present hypoglycemic activity in animal model, but at high doses the plant may cause severe intoxication.     

CYP2C9 VKORC1基因多态性指导对非瓣膜性心房颤动患者华法林剂量的影响

目的 探讨CYP2C9、VKORC1基因多态性对非瓣膜性心房颤动（NVAF）患者华法林应用剂量的影响。方法 选择合肥市第二人民医院2017年11月至2019年10月收治的214例NVAF患者,采用随机数字表法分为基因指导组（69例）与对照组（145例）,基因指导组检测VKORC1、CYP2C9基因多态性,对照组按常规剂量给予华法林,比较两组患者华法林起效剂量、有效剂量、起效时间及第14、21天达稳定剂量患者比例等指标。结果 基因指导组患者在华法林应用初始剂量为（1.67±1.63）mg、稳定剂量为（2.02±0.94）mg,均低于对照组,起效时间为（7.62±2.87）d,短于对照组短,差异有统计学意义（P<0.05）。CYP2C9、VKORC1组华法林应用初始剂量、稳定剂量均低于对照组,起效时间短于对照组,差异有统计学意义（P<0.05）。基因指导组第14、21天达稳定剂量患者比例（76.44%、98.27%）高于对照组,差异有统计学意义（P<0.05）。结论 VKORC1、CYP2C9基因多态性检测结合NVAF患者临床特点可为临床精准合理应用华法林提供参考。     

Antidiabetic and hypolipidemic activities of Kigelia pinnata flowers extract in streptozotocin induced diabetic rats

Objective

To evaluate antidiabetic and hypolipidemic activities of Kigelia pinnata methanolic flowers extract in streptozotocin (STZ) induced diabetic wistar rat.

Methods

Rats were made diabetic by a single dose of STZ at 60 mg/kg body weight i.p. The blood glucose level was checked before and 72 h after STZ injection to confirm the development of diabetes. The flower extract and glibenclamide were administered orally at the doses of 250 and 500 mg/kg body weight for 21 days.

Results

Daily oral treatment with the extract and standard drug for 21 days significantly reduced blood glucose, serum cholesterol and triglycerides levels. High density lipoprotein-cholesterol level was found to be improved (P<0.01) as compared to diabetic control group.

Conclusions

It is concluded that Kigellia pinnata flowers extract have significant antidiabetic and hypolipidemic effect.     

Hybrid methods for improving information access in clinical documents: concept,assertion, and relation identification

Objective

This paper describes the approaches the authors developed while participating in the i2b2/VA 2010 challenge to automatically extract medical concepts and annotate assertions on concepts and relations between concepts.

Design

The authors''approaches rely on both rule-based and machine-learning methods. Natural language processing is used to extract features from the input texts; these features are then used in the authors'' machine-learning approaches. The authors used Conditional Random Fields for concept extraction, and Support Vector Machines for assertion and relation annotation. Depending on the task, the authors tested various combinations of rule-based and machine-learning methods.

Results

The authors''assertion annotation system obtained an F-measure of 0.931, ranking fifth out of 21 participants at the i2b2/VA 2010 challenge. The authors'' relation annotation system ranked third out of 16 participants with a 0.709 F-measure. The 0.773 F-measure the authors obtained on concept extraction did not make it to the top 10.

Conclusion

On the one hand, the authors confirm that the use of only machine-learning methods is highly dependent on the annotated training data, and thus obtained better results for well-represented classes. On the other hand, the use of only a rule-based method was not sufficient to deal with new types of data. Finally, the use of hybrid approaches combining machine-learning and rule-based approaches yielded higher scores.     

Targeted screening for pediatric conditions with the CHICA system

Objective

The Child Health Improvement through Computer Automation (CHICA) system is a decision-support and electronic-medical-record system for pediatric health maintenance and disease management. The purpose of this study was to explore CHICA''s ability to screen patients for disorders that have validated screening criteria—specifically tuberculosis (TB) and iron-deficiency anemia.

Design

Children between 0 and 11 years were randomized by the CHICA system. In the intervention group, parents were asked about TB and iron-deficiency risk, and physicians received a tailored prompt. In the control group, no screens were performed, and the physician received a generic prompt about these disorders.

Results

1123 participants were randomized to the control group and 1116 participants to the intervention group. Significantly more people reported positive risk factors for iron-deficiency anemia in the intervention group (17.5% vs 3.1%, OR 6.6, 95% CI 4.5 to 9.5). In general, far fewer parents reported risk factors for TB than for iron-deficiency anemia. Again, there were significantly higher detection rates of positive risk factors in the intervention group (1.8% vs 0.8%, OR 2.3, 95% CI 1.0 to 5.0).

Limitations

It is possible that there may be more positive screens without improving outcomes. However, the guidelines are based on studies that have evaluated the questions the authors used as sensitive and specific, and there is no reason to believe that parents misunderstood them.

Conclusions

Many screening tests are risk-based, not universal, leaving physicians to determine who should have a further workup. This can be a time-consuming process. The authors demonstrated that the CHICA system performs well in assessing risk automatically for TB and iron-deficiency anemia.     

Machine-learned solutions for three stages of clinical information extraction: the state of the art at i2b2 2010

Objective

As clinical text mining continues to mature, its potential as an enabling technology for innovations in patient care and clinical research is becoming a reality. A critical part of that process is rigid benchmark testing of natural language processing methods on realistic clinical narrative. In this paper, the authors describe the design and performance of three state-of-the-art text-mining applications from the National Research Council of Canada on evaluations within the 2010 i2b2 challenge.

Design

The three systems perform three key steps in clinical information extraction: (1) extraction of medical problems, tests, and treatments, from discharge summaries and progress notes; (2) classification of assertions made on the medical problems; (3) classification of relations between medical concepts. Machine learning systems performed these tasks using large-dimensional bags of features, as derived from both the text itself and from external sources: UMLS, cTAKES, and Medline.

Measurements

Performance was measured per subtask, using micro-averaged F-scores, as calculated by comparing system annotations with ground-truth annotations on a test set.

Results

The systems ranked high among all submitted systems in the competition, with the following F-scores: concept extraction 0.8523 (ranked first); assertion detection 0.9362 (ranked first); relationship detection 0.7313 (ranked second).

Conclusion

For all tasks, we found that the introduction of a wide range of features was crucial to success. Importantly, our choice of machine learning algorithms allowed us to be versatile in our feature design, and to introduce a large number of features without overfitting and without encountering computing-resource bottlenecks.     

Long-term spatial memory and morphological changes in hippocampus of Wistar rats exposed to smoke from Carica papaya leaves

Objective

To investigate the effects of smoking of dried leaves of Carica papaya (pawpaw) based on ethnopharmacological information which indicated that smoking of papaya leaves could influence motor performance and learning.

Methods

Twenty-four rats were used for the study, and were grouped into four groups. Groups 1 served as the control (not exposed to papaya leaves smoke), while Groups 2, 3 and 4 were exposed to smoke from 6.25 g, 12.50 g and 18.75 g of dry pawpaw leaves respectively in a smoking chamber twice daily for 21 d with each exposure lasting for 3 min. Lastly, hippocampus was harvested in each group for histological study.

Results

The results showed that there were significant (P<0.05) increases in mean of recall latencies of long-term spatial memory in the animal administered the high dose while the other groups had significantly (P<0.05) lower frequencies. Histological investigation showed signs of mild neural degeneration in high dose group and hypochromic appearance of the Nissl substance in all treated groups.

Conclusions

In conclusion, the findings from this study has demonstrated that smoking of papaya leaves has the ability to maintain an intact long-term spatial memory at all doses but retrieving such memory is faster with the low and medium dosages.     

Protecting count queries in study design

Objective

Today''s clinical research institutions provide tools for researchers to query their data warehouses for counts of patients. To protect patient privacy, counts are perturbed before reporting; this compromises their utility for increased privacy. The goal of this study is to extend current query answer systems to guarantee a quantifiable level of privacy and allow users to tailor perturbations to maximize the usefulness according to their needs.

Methods

A perturbation mechanism was designed in which users are given options with respect to scale and direction of the perturbation. The mechanism translates the true count, user preferences, and a privacy level within administrator-specified bounds into a probability distribution from which the perturbed count is drawn.

Results

Users can significantly impact the scale and direction of the count perturbation and can receive more accurate final cohort estimates. Strong and semantically meaningful differential privacy is guaranteed, providing for a unified privacy accounting system that can support role-based trust levels. This study provides an open source web-enabled tool to investigate visually and numerically the interaction between system parameters, including required privacy level and user preference settings.

Conclusions

Quantifying privacy allows system administrators to provide users with a privacy budget and to monitor its expenditure, enabling users to control the inevitable loss of utility. While current measures of privacy are conservative, this system can take advantage of future advances in privacy measurement. The system provides new ways of trading off privacy and utility that are not provided in current study design systems.