Sentinel surveillance of HIV-1 transmitted drug resistance, acute infection and recent infection.

BackgroundHIV-1 acute infection, recent infection and transmitted drug resistance screening was integrated into voluntary HIV counseling and testing (VCT) services to enhance the existing surveillance program in San Francisco. This study describes newly-diagnosed HIV cases and characterizes correlates associated with infection.Methodology/principal findingsA consecutive sample of persons presenting for HIV VCT at the municipal sexually transmitted infections (STI) clinic from 2004 to 2006 (N = 9,868) were evaluated by standard enzyme-linked immunoassays (EIA). HIV antibody-positive specimens were characterized as recent infections using a less-sensitive EIA. HIV-RNA pooled testing was performed on HIV antibody-negative specimens to identify acute infections. HIV antibody-positive and acute infection specimens were evaluated for drug resistance by sequence analysis. Multivariable logistic regression was performed to evaluate associations. The 380 newly-diagnosed HIV cases included 29 acute infections, 128 recent infections, and 47 drug-resistant cases, with no significant increases or decreases in prevalence over the three years studied. HIV-1 transmitted drug resistance prevalence was 11.0% in 2004, 13.4% in 2005 and 14.9% in 2006 (p = 0.36). Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) was the most common pattern detected, present in 28 cases of resistance (59.6%). Among MSM, recent infection was associated with amphetamine use (AOR = 2.67; p<0.001), unprotected anal intercourse (AOR = 2.27; p<0.001), sex with a known HIV-infected partner (AOR = 1.64; p = 0.02), and history of gonorrhea (AOR = 1.62; p = 0.03).ConclusionsNew HIV diagnoses, recent infections, acute infections and transmitted drug resistance prevalence remained stable between 2004 and 2006. Resistance to NNRTI comprised more than half of the drug-resistant cases, a worrisome finding given its role as the backbone of first-line antiretroviral therapy in San Francisco as well as worldwide. The integration of HIV-1 drug resistance, recent infection, and acute infection testing should be considered for existing HIV/STI surveillance and prevention activities, particularly in an era of enhanced efforts for early diagnosis and treatment

Geostatistical radar-raingauge combination with nonparametric correlograms: methodological considerations and application in Switzerland

Modelling spatial covariance is an essential part of all geostatistical methods. Traditionally, parametric semivariogram models are fit from available data. More recently, it has been suggested to use nonparametric correlograms obtained from spatially complete data fields. Here, both estimation techniques are compared. Nonparametric correlograms are shown to have a substantial negative bias. Nonetheless, when combined with the sample variance of the spatial field under consideration, they yield an estimate of the semivariogram that is unbiased for small lag distances. This justifies the use of this estimation technique in geostatistical applications. Various formulations of geostatistical combination (Kriging) methods are used here for the construction of hourly precipitation grids for Switzerland based on data from a sparse realtime network of raingauges and from a spatially complete radar composite. Two variants of Ordinary Kriging (OK) are used to interpolate the sparse gauge observations. In both OK variants, the radar data are only used to determine the semivariogram model. One variant relies on a traditional parametric semivariogram estimate, whereas the other variant uses the nonparametric correlogram. The variants are tested for three cases and the impact of the semivariogram model on the Kriging prediction is illustrated. For the three test cases, the method using nonparametric correlograms performs equally well or better than the traditional method, and at the same time offers great practical advantages. Furthermore, two variants of Kriging with external drift (KED) are tested, both of which use the radar data to estimate nonparametric correlograms, and as the external drift variable. The first KED variant has been used previously for geostatistical radar-raingauge merging in Catalonia (Spain). The second variant is newly proposed here and is an extension of the first. Both variants are evaluated for the three test cases as well as an extended evaluation period. It is found that both methods yield merged fields of better quality than the original radar field or fields obtained by OK of gauge data. The newly suggested KED formulation is shown to be beneficial, in particular in mountainous regions where the quality of the Swiss radar composite is comparatively low. An analysis of the Kriging variances shows that none of the methods tested here provides a satisfactory uncertainty estimate. A suitable variable transformation is expected to improve this

Novel measures of inflammation and insulin resistance are related to obesity and fitness in a diverse sample of 11-14 year-olds:The HEALTHY Study

BACKGROUND: GlycA is a novel serum marker of systemic inflammation. There is no information on GlycA in pediatric populations, how it differs by gender or its association with body mass index (BMI) or fitness. LP-IR is a serum measure of insulin resistance which is related to changes in BMI group in adolescents, but its relationship with fitness is unknown. The current study examined the independent associations between fitness and BMI with GlycA and LP-IR among US adolescents. METHODS: Participants were 1664 US adolescents from the HEALTHY study with complete 6th and 8th grade BMI, fitness and blood data. GlycA and LP-IR were measured by NMR spectroscopy. Three BMI groups and three fitness groups were created. Linear mixed models examined associations between GlycA, LP-IR, fitness and BMI. RESULTS: LP-IR decreased between 6th and 8th grade. GlycA increased among girls but decreased among boys. At 8th grade, median GlycA values were 27 (7.6%) μmol/l higher (381 versus 354) for girls than boys. Median GlycA 6th grade values were 9% higher in obese girls than healthy weight girls. Overall there was strong evidence (P CONCLUSIONS: GlycA was associated with BMI and fitness among in US adolescents. These findings suggest that there are independent effects for BMI and fitness group with both GlycA and LP-IR. Future studies should validate the role of GlycA and LP-IR to evaluate the effects of interventions to modify obesity and fitness in order to improve systemic inflammation and insulin resistance.International Journal of Obesity accepted article preview online, 04 May 2016. doi:10.1038/ijo.2016.84

Insights into the pathogenesis of nicotine addiction. Could a salivary biosensor be useful in Nicotine Replacement Therapy (NRT)?

Nicotine has gained the attention of the medical community due to its insidious addictive mechanisms which lead to chronic consumption. The multitude of compounds derived from tobacco smoke have local and systemic negative impacts, resulting in a large number of smoking-related pathologies. The present review offers insights into nicotine addiction physiopathology, as well as social and medical implications, with emphasis on its correlation with Advanced Glycation End Products (AGEs). Therapeutic strategies and new approaches to nicotine assessment and cessation treatment are discussed, noting that such strategies could take into account the possibility of slow and gradual nicotine release from a device attached to a prosthetic piece, based on salivary nicotine-concentration feedback. This approach could offer real-time and home-based self-therapy monitoring by the physician and the patient for follow-up and improve long-term cessation treatment success- Graphical abstract

Hereditary Systemic Angiopathy (HSA) with cerebral calcifications, retinopathy, progressive nephropathy, and hepatopathy

Several hereditary conditions affecting cerebral, retinal and systemic microvessels have recently been described. They include CADASIL, CRV, and HERNS. We here report on a variant form of a hereditary systemic angiopathy (HSA) affecting two generations of a Caucasian family. Clinical symptoms of HSA appear in the mid-forties and are characterized by visual impairment, migrainelike headache, skin rash, epileptic seizures, progressive motor paresis and cognitive decline. Late symptoms include hepatic and renal failure. Retinal capillary microaneurysms and arteriolar tortuosity are associated with marked optic disc atrophy. Radiological hallmarks consist of multiple cerebral calcifications and tumor-like subcortical white matter lesions. Brain, peripheral nerve, muscle, kidney and colon biopsies have revealed a multi organ small vessel involvement with partly altered endothelium, perivascular inflammation and thrombotic microangiopathy. No curative therapeutic options are known for hereditary cerebral vasculopathies. The use of cyclophosphamide, azathioprine and methotrexate was of no benefit in our cases of HSA. Early diagnosis of hereditary systemic angiopathies is important in order to prevent patients from repetitive invasive diagnostic measures and to avoid the use of inappropriate and potentially harmful drug

The effects of UV radiation and electron bombardment on the flashover characteristics of alumina based high voltage insulators in vacuum

The effects of UV and electron bombardment on the flashover characteristics of highly stressed alumina insulators in vacuum were investigated as part of a project to improve the performance of high voltage insulators in large particle accelerators at CERN. An experimental system has been developed which allowed photon and electron bombardment of stressed insulator samples under vacuum, in order to investigate the causes and characteristics of insulator flashover, and to identify sample preparations which could improve insulator performance

Normal-Conducting Separation and Compensation Dipoles for the LHC Experimental Insertions

The experimental insertions of the LHC make use of normal-conducting magnets to provide for part of the beam separation and to compensate the effect of two large spectrometer dipoles. Three different types with respect to the length were designed and are based on the same type of lamination. The main type of magnet MBXW has a core length of 3.4 m while the MBXWT and MBXWS magnets are 1.5 m and 0.75 m long versions respectively. The magnet design was done in collaboration between CERN and BINP and the dipole magnets are produced by BINP. So far all three MBXWS magnets, all three MBXWT magnets and fifteen of twenty-nine MBXW magnets have been manufactured and delivered to CERN. The report presents the main design issues and results of the acceptance tests including mechanical, electrical and magnetic field measurements