Progress in HPV vaccination in low- and lower-middle-income countries.

The past 10 years have seen remarkable progress in the global scale-up of human papillomavirus (HPV) vaccinations. Forty-three low- and lower-middle-income countries (LLMICs) have gained experience in delivering this vaccine to young adolescent girls through pilot programs, demonstration programs, and national introductions and most of these have occurred in the last 4 years. The experience of Senegal is summarized as an illustrative country case study. Publication of numerous delivery experiences and lessons learned has demonstrated the acceptability and feasibility of HPV vaccinations in LLMICs. Four areas require dedicated action to overcome remaining challenges to national scaling-up: maintaining momentum politically, planning successfully, securing financing, and fostering sustainability. Advances in policy, programming, and science may help accelerate reaching 30 million girls in LLMICs with HPV vaccine by 2020

Exposures of children in Canada to 60-Hz magnetic and electric fields

Objectives This study characterized personal exposures of Canadian children to 60-Hz magnetic and electric fields and explained the variability. Methods Altogether 382 Canadian children up to 15 years of age wore meters recording 60-Hz electric and magnetic fields over 2 days. Meter location was recorded. Thereafter, meters recorded fields in the center of the children's bedrooms for 24 h. Personal exposures were calculated for home, school or day care, outside the home, bedroom at night, and all categories combined (total). Results The arithmetic mean (AM) was 0.121 mT [geometric mean (GM): 0.085 mT), range 0.01-0.8 mT] for total magnetic fields. Fifteen percent of the total exposures exceeded 0.2 mT. The AM of the total electric fields was 14.4 (GM 12.3, range 0.82-64.7) V/m. By location category, the highest and lowest magnetic fields occurred at home during the day (0.142 mT) and during the night (0.112 mT), respectively. Measurements during sleep provided the highest correlation with total magnetic field exposure. Province of measurement explained 14.7% of the variation in the logarithms of total magnetic fields, and season accounted for an additional 1.5%. Electric heating, air conditioning, and housing type appeared to be useful predictors of magnetic field exposures. Conclusions In identifying differences in children's magnetic field exposures between provinces, measurements at night provided the best surrogate for predicting total magnetic field exposure, followed by at-home exposure and 24-h bedroom measurements. Electrical heating and air conditioning, wiring type, and type of housing appear to be promising indicators of magnetic field levels

Mouse hypothalamic GT1-7 cells demonstrate AMPK-dependent intrinsic glucose-sensing behaviour.

AIMS/HYPOTHESIS: Hypothalamic glucose-excited (GE) neurons contribute to whole-body glucose homeostasis and participate in the detection of hypoglycaemia. This system appears defective in type 1 diabetes, in which hypoglycaemia commonly occurs. Unfortunately, it is at present unclear which molecular components required for glucose sensing are produced in individual neurons and how these are functionally linked. We used the GT1-7 mouse hypothalamic cell line to address these issues. METHODS: Electrophysiological recordings, coupled with measurements of gene expression and protein levels and activity, were made from unmodified GT1-7 cells and cells in which AMP-activated protein kinase (AMPK) catalytic subunit gene expression and activity were reduced. RESULTS: Hypothalamic GT1-7 neurons express the genes encoding glucokinase and ATP-sensitive K(+) channel (K(ATP)) subunits K ( ir ) 6.2 and Sur1 and exhibit GE-type glucose-sensing behaviour. Lowered extracellular glucose concentration hyperpolarised the cells in a concentration-dependent manner, an outcome that was reversed by tolbutamide. Inhibition of glucose uptake or metabolism hyperpolarised cells, showing that energy metabolism is required to maintain their resting membrane potential. Short hairpin (sh)RNA directed to Ampkα2 (also known as Prkaa2) reduced GT1-7 cell AMPKα2, but not AMPKα1, activity and lowered the threshold for hypoglycaemia-induced hyperpolarisation. shAmpkα1 (also known as Prkaa1) had no effect on glucose-sensing or AMPKα2 activity. Decreased uncoupling protein 2 (Ucp2) mRNA was detected in AMPKα2-reduced cells, suggesting that AMPKα2 regulates UCP2 levels. CONCLUSIONS/INTERPRETATION: We have demonstrated that GT1-7 cells closely mimic GE neuron glucose-sensing behaviour, and reducing AMPKα2 blunts their responsiveness to hypoglycaemic challenge, possibly by altering UCP2 activity. These results show that suppression of AMPKα2 activity inhibits normal glucose-sensing behaviour and may contribute to defective detection of hypoglycaemia.This study was funded by: grants from the Wellcome Trust (grant numbers 068692 and 086989) and Diabetes UK (grant number RD08/0003681) to M.L.J. Ashford; a Juvenile Diabetes Research Foundation (JDRF) Postdoctoral Fellowship to C. Beall (grant number 3-576-2010); grants from JDRF and European Foundation for the study of Diabetes to R.J. McCrimmon, and from the British Heart Foundation to A. Jovanović

Clinical effectiveness of unilateral deep brain stimulation in Tourette syndrome

Dysfunctional basal ganglia loops are thought to underlie the clinical picture of Tourette syndrome (TS). By altering dopaminergic activity in the affected neural structures, bilateral deep brain stimulation is assumed to have a modulatory effect on dopamine transmission resulting in an amelioration of tics. While the majority of published case reports deals with the application of bilateral stimulation, the present study aims at informing about the high effectiveness of unilateral stimulation of pallidal and nigral thalamic territories in TS. Potential implications and gains of the unilateral approach are discussed

Influence of Dry Soil on the Ability of Formosan Subterranean Termites, Coptotermes formosanus, to Locate Food Sources

The effect of barriers of dry soil on the ability of Formosan subterranean termites, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae), to construct tunnels and find food was evaluated. Termite movement and wood consumption in a three—chambered apparatus were compared between treatments with dry soil in the center container and treatments where the soil in the center container was moist. When a wood block was located in the release container, termites fed significantly more on that block, regardless of treatment or soil type. In the treatment with dry clay, none of the termites tunneled through the dry clay barrier to reach the distal container. When termites had to tunnel through a barrier of dry sand, topsoil, or clay to reach the sole wood block, there was no effect on wood consumption for the sand treatment, but there was significantly less feeding on wood in the treatments with dry topsoil or clay. When foraging arenas had a section of dry sand in the center, the dry sand significantly reduced tunneling in the distal section after 3 days, but not after 10 days. There was a highly significant effect on the ability of termites to colonize food located in dry sand. Only one feeding station located in dry sand was colonized by termites, compared with 11 feeding stations located in moist sand

Inappropriate prescribing and adverse drug events in older people

Inappropriate prescribing (IP) in older patients is highly prevalent and is associated with an increased risk of adverse drug events (ADEs), morbidity, mortality and healthcare utilisation. Consequently, IP is a major safety concern and with changing population demographics, it is likely to become even more prevalent in the future. IP can be detected using explicit or implicit prescribing indicators. Theoretically, the routine clinical application of these IP criteria could represent an inexpensive and time efficient method to optimise prescribing practice. However, IP criteria must be sensitive, specific, have good inter-rater reliability and incorporate those medications most commonly associated with ADEs in older people. To be clinically relevant, use of prescribing appropriateness tools must translate into positive patient outcomes, such as reduced rates of ADEs. To accurately measure these outcomes, a reliable method of assessing the relationship between the administration of a drug and an adverse clinical event is required. The Naranjo criteria are the most widely used tool for assessing ADE causality, however, they are often difficult to interpret in the context of older patients. ADE causality criteria that allow for the multiple co-morbidities and prescribed medications in older people are required. Ultimately, the current high prevalence of IP and ADEs is unacceptable. IP screening criteria need to be tested as an intervention to assess their impact on the incidence of ADEs in vulnerable older patients. There is a role for IP screening tools in everyday clinical practice. These should enhance, not replace good clinical judgement, which in turn should be based on sound pharmacogeriatric training

Is implementing a post-lunch nap beneficial on evening performance, following two nights partial sleep restriction?

We have investigated the effects that partial-sleep-restriction (PSR0, 4-h sleep retiring at 02:30 and waking at 06:30 h for two consecutive nights) have on 07:30 and 17:00 h cognitive and submaximal weightlifting; and whether this performance improves at 17:00 h following a 13:00 h powernap (0, 30 or 60-min). Fifteen resistance-trained males participated in this study. Prior to the experimental protocol, one repetition max (1RM) bench press and back squat, normative habitual sleep and food intake were recorded. Participants were familiarised with the testing protocol, then completed three experimental conditions: (i) PSR with no nap (PSR0); (ii) PSR with a 30-min nap (PSR30) and (iii) PSR with a 60-min nap (PSR60). Conditions were separated by 7 days with trial order counterbalanced. Intra-aural temperature, Profile of Mood Scores, word-colour interference, alertness and tiredness values were measured at 07:30, 11:00, 14:00, 17:00 h on the day of exercise protocol. Following final temperature measurements at 07:30 h and 17:00 h, participants completed a 5-min active warm-up before performing three repetitions of left and right-hand grip strength, followed by three repetitions at each incremental load (40, 60 and 80% of 1RM) for bench press and back squat, with a 5-min recovery between each repetition. A linear encoder was attached perpendicular to the bar used for the exercises. Average power (AP), average velocity (AV), peak velocity (PV), displacement (D) and time-to-peak velocity (tPV) were measured (MuscleLab software) during the concentric phase of the movements. Data were analysed using general linear models with repeated measures. The main findings were that implementing a nap at 13:00 h had no effect on measures of strength (grip, bench press or back squat). There was a main effect for time of day with greatest performance at 17:00 h for measures of strength. In addition to a significant effect for “load” on the bar for bench press and back squat where AP, AV, PV, D values were greatest at 40% (P < 0.05) and decreased with increased load, whereas tPV and RPE values increased with load; despite this no interaction of “load and condition” were present. A post lunch nap of 30- and 60-minute durations improved mood state, with feelings of alertness, vigour and happiness highest at 17:00 h, in contrast to confusion, tiredness and fatigue (P < 0.05), which were greater in the morning (07:30 h). The word-colour interference test, used as an indicator of cognitive function, reported significant main effect for condition, with the highest total test score in PSR60 condition (P = 0.015). In summary, unlike strength measures the implementation of a 30 or 60-minute nap improved cognitive function when in a partially sleep restricted state, compared to no nap

Behavioral determinants as predictors of return to work after long-term sickness absence: an application of the theory of planned behavior

Background The aim of this prospective, longitudinal cohort study was to analyze the association between the three behavioral determinants of the theory of planned behavior (TPB) model-attitude, subjective norm and self-efficacy-and the time to return-to-work (RTW) in employees on long-term sick leave. Methods The study was based on a sample of 926 employees on sickness absence (maximum duration of 12 weeks). The employees filled out a baseline questionnaire and were subsequently followed until the tenth month after listing sick. The TPB-determinants were measured at baseline. Work attitude was measured with a Dutch language version of the Work Involvement Scale. Subjective norm was measured with a self-structured scale reflecting a person's perception of social support and social pressure. Self-efficacy was measured with the three subscales of a standardised Dutch version of the general self-efficacy scale (ALCOS): willingness to expend effort in completing the behavior, persistence in the face of adversity, and willingness to initiate behavior. Cox proportional hazards regression analyses were used to identify behavioral determinants of the time to RTW. Results Median time to RTW was 160 days. In the univariate analysis, all potential prognostic factors were significantly associated (P < 0.15) with time to RTW: work attitude, social support, and the three subscales of self-efficacy. The final multivariate model with time to RTW as the predicted outcome included work attitude, social support and willingness to expend effort in completing the behavior as significant predictive factors. Conclusions This prospective, longitudinal cohort-study showed that work attitude, social support and willingness to expend effort in completing the behavior are significantly associated with a shorter time to RTW in employees on long-term sickness absence. This provides suggestive evidence for the relevance of behavioral characteristics in the prediction of duration of sickness absence. It may be a promising approach to address the behavioral determinants in the development of interventions focusing on RTW in employees on long-term sick leave

The effect of oxygen saturation targeting on retinal blood vessel growth using retinal image data from the BOOST-II UK Trial

Purpose: Retinopathy of prematurity (ROP) is a disorder of developing retinal blood vessels in preterm infants. The purpose of this nested study was to investigate the effects of higher (91-95%) and lower (85-89%) oxygen saturation (SpO2) targeting on retinal blood vessel growth in preterm infants. Methods: Retinal blood vessel growth in the higher (91-95%) and lower (85-89%) oxygen saturation (SpO2) targeting groups was compared. Suitable RetCam (Clarity, Pleasanton, CA, USA) images collected in the BOOST-II UK trial were used. The distances between the centre of the optic disc and the ROP ridge in the temporal and nasal retina were measured in pixel units. Results: Images from 38 infants were studied, 20 from the higher SpO2 target group and 18 from the lower SpO2 target group. On average, temporal blood vessels extended further from the optic disc than nasal blood vessels, mean (standard deviation (SD)) 463.39 (55.05) pixels compared with 360.13 (44.47) pixels, respectively, P&lt;0.0001. Temporal blood vessels extended less far from the optic disc in the higher SpO2 target group than in the lower SpO2 target group: mean (SD) 449.83 (56.16) pixels compared with 480.02 (49.94), respectively, P=0.055. Nasal retinal blood vessel measurements were broadly similar in the higher and lower SpO2 target groups; mean (SD) 353.96 (41.95) compared with 370.00 (48.82) pixels, respectively, P=0.38. Conclusions: Relatively high oxygen saturation targeting (91-95%) was associated with a trend (P=0.055) towards reduced retinal blood vessel growth in this study of preterm infants