Clinical evaluation of the GlucoWatch® biographer: a continual, non-invasive glucose monitor for patients with diabetes

A device providing frequent, automatic, and non-invasive glucose measurements for persons with diabetes has been developed: the GlucoWatch^® biographer. This device extracts glucose through intact skin via reverse iontophoresis where it is detected by an amperometric biosensor. The biographer can provide glucose readings every 20 min for 12 h. The performance of this device was evaluated in two large clinical studies in a controlled clinical environment (n=231), and the home environment (n=124). Accuracy of the biographer was evaluated by comparing the automatic biographer readings to serial finger-stick blood glucose (BG) measurements. Biographer performance was comparable in both environments. Mean difference between biographer and finger-stick measurements was −0.01 and 0.26 mmol l⁻¹ for the clinical and home environments, respectively. The mean absolute value of the relative difference was 1.06 and 1.18 mmol l⁻¹ for the same studies. Correlation coefficient (r) between biographer and finger-stick measurements was 0.85 and 0.80 for the two studies. In both studies, over 94% of the biographer readings were in the clinically acceptable A+B region of the Clarke Error Grid. A slight positive bias is observed for the biographer readings at low BG levels. Biographer accuracy is relatively constant over all rates of BG changes, except when BG decreases more than 10 mmol l⁻¹ h⁻¹, which occurred for only 0.2% of points in the home environment study. Biographer precision, as measured by CV%, is approx. 10%. Skin irritation, characterized by erythema and edema, was either non-existent or mild in >90% of subjects and resolved in virtually all subjects without treatment in several days.     

DNA Vaccine Delivered by a Needle-Free Injection Device Improves Potency of Priming for Antibody and CD8+ T-Cell Responses after rAd5 Boost in a Randomized Clinical Trial

Background

DNA vaccine immunogenicity has been limited by inefficient delivery. Needle-free delivery of DNA using a CO₂-powered Biojector® device was compared to delivery by needle and syringe and evaluated for safety and immunogenicity.

Methods

Forty adults, 18–50 years, were randomly assigned to intramuscular (IM) vaccinations with DNA vaccine, VRC-HIVDNA016-00-VP, (weeks 0, 4, 8) by Biojector® 2000™ or needle and syringe (N/S) and boosted IM at week 24 with VRC-HIVADV014-00-VP (rAd5) with N/S at 10¹⁰ or 10¹¹ particle units (PU). Equal numbers per assigned schedule had low (≤500) or high (>500) reciprocal titers of preexisting Ad5 neutralizing antibody.

Results

120 DNA and 39 rAd5 injections were given; 36 subjects completed follow-up research sample collections. IFN-γ ELISpot response rates were 17/19 (89%) for Biojector® and 13/17 (76%) for N/S delivery at Week 28 (4 weeks post rAd5 boost). The magnitude of ELISpot response was about 3-fold higher in Biojector® compared to N/S groups. Similar effects on response rates and magnitude were observed for CD8+, but not CD4+ T-cell responses by ICS. Env-specific antibody responses were about 10-fold higher in Biojector-primed subjects.

Conclusions

DNA vaccination by Biojector® was well-tolerated and compared to needle injection, primed for greater IFN-γ ELISpot, CD8+ T-cell, and antibody responses after rAd5 boosting.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00109629","term_id":"NCT00109629"}}NCT00109629     

新疆若羌石灰华中的植物化石及古环境*

根据首次从富阳西湖组发现的孢子及其垂直分布特征,划分出下段 LH 组合和上段 DP 组合,分别归入晚泥盆世法门晚期(斯图年期)和早石炭世早期(杜内早期),即泥盆-石炭系界线通过西湖组内部,与江苏五通组类似.     

What Kind of Capsule Endoscope Is Suitable for a Controllable Self-Propelling Capsule Endoscope? Experimental Study Using a Porcine Stomach Model for Clinical Application (with Videos)

BackgroundWe have been developing the Self-Propelling Capsule Endoscope (SPCE) that allows for controllability from outside of the body and real-time observation. What kind of capsule endoscope (CE) is suitable for a controllable SPCE is unclear and a very critical point for clinical application. We compared observing ability of three kinds of SPCEs with different viewing angles and frame rates.MethodsEleven buttons were sewed in an excised porcine stomach. Four examiners controlled the SPCE using PillCamSB2, -ESO2, and -COLON2 (Given Imaging Ltd., Israel), for 10 minutes each with the aim of detecting as many buttons and examining them as closely as possible. The ability to find lesions was assessed based on the number of detected buttons. The SPCE-performance score (SPS) was used to evaluate the ability to examine the lesions in detail.ResultsThe SPCE-ESO2, -COLON2, and -SB2 detected 11 [interquartile range (IQR): 0], 10.5 (IQR, 0.5), and 8 (IQR, 1.0) buttons, respectively. The SPCE-ESO2 and -COLON2 had a significantly better ability to detect lesions than the -SB2 (p < 0.05). The SPCE-ESO2, -COLON2, and -SB2 had significantly different SPS values of 22 (IQR, 0), 16.5 (IQR, 1.5), and 14 (IQR, 1.0), respectively (p < 0.05 for all comparisons; SPCE-SB2 vs. -ESO2, -SB2 vs. -COLON2, and -ESO2 vs. -COLON2).ConclusionsPillCamESO2 is most suitable in different three CEs for SPCE for examining lesions in detail of the stomach.     

Estimating the Impact of Plasma HIV-1 RNA Reductions on Heterosexual HIV-1 Transmission Risk

Background

The risk of sexual transmission of HIV-1 is strongly associated with the level of HIV-1 RNA in plasma making reduction in HIV-1 plasma levels an important target for HIV-1 prevention interventions. A quantitative understanding of the relationship of plasma HIV-1 RNA and HIV-1 transmission risk could help predict the impact of candidate HIV-1 prevention interventions that operate by reducing plasma HIV-1 levels, such as antiretroviral therapy (ART), therapeutic vaccines, and other non-ART interventions.

Methodology/Principal Findings

We use prospective data collected from 2004 to 2008 in East and Southern African HIV-1 serodiscordant couples to model the relationship of plasma HIV-1 RNA levels and heterosexual transmission risk with confirmation of HIV-1 transmission events by HIV-1 sequencing. The model is based on follow-up of 3381 HIV-1 serodiscordant couples over 5017 person-years encompassing 108 genetically-linked HIV-1 transmission events. HIV-1 transmission risk was 2.27 per 100 person-years with a log-linear relationship to log₁₀ plasma HIV-1 RNA. The model predicts that a decrease in average plasma HIV-1 RNA of 0.74 log₁₀ copies/mL (95% CI 0.60 to 0.97) reduces heterosexual transmission risk by 50%, regardless of the average starting plasma HIV-1 level in the population and independent of other HIV-1-related population characteristics. In a simulated population with a similar plasma HIV-1 RNA distribution the model estimates that 90% of overall HIV-1 infections averted by a 0.74 copies/mL reduction in plasma HIV-1 RNA could be achieved by targeting this reduction to the 58% of the cohort with plasma HIV-1 levels ≥4 log₁₀ copies/mL.

Conclusions/Significance

This log-linear model of plasma HIV-1 levels and risk of sexual HIV-1 transmission may help estimate the impact on HIV-1 transmission and infections averted from candidate interventions that reduce plasma HIV-1 RNA levels.     

新疆昆仑山黄羊岭—木孜塔格一带早二叠世的(竹蜓)

本文报道了新疆昆仑山黄羊岭—木孜塔格地区下二叠统黄羊岭群的分布、层序划分及对比;首次对黄羊岭群所含?类进行了研究和描述。共描述早三叠世?类15属26种,其中4个新种,1个新亚种,2个未定种。 黄羊岭群下亚群和华南的栖霞组大致可以对比,黄羊岭群上亚群和华南茅口组大致可以对比。黄羊岭群的早二叠世?类,属典型的特提斯海暖水?类,生物地理分区上属特提斯大区的华夏-特提斯区。