How Will Energy Demand Develop in the Developing World?

Most of the medium-run growth in energy demand is forecast to come from the developing world, which consumed more total units of energy than the developed world in 2007. We argue that the main driver of the growth is likely to be increased incomes among the poor and near-poor. We document that as households come out of poverty and join the middle class, they acquire appliances, such as refrigerators, and vehicles for the first time. These new goods require energy to use and energy to manufacture. The current forecasts for energy demand in the developing world may be understated because they do not accurately capture the dramatic increase in demand associated with poverty reduction.

Book Review

Reviewing Martin J. Norris, Your Boat and the Law, Lawyers Co-operative Publishing Company, 196

Rotor performance characteristics from an aeroacoustic helicopter wind-tunnel test program

An investigation of helicopter rotor noise at model scale was conducted in the Langley 4 by 7 meter tunnel. The program described was the first of a planned three-phase project whose purpose was to examine the characteristic noise mechanism involved in main rotor/tail rotor interaction noise. This first phase was conducted with a main rotor only, in order to identify the characteristic noise generated by only the main rotor. The aerodynamic operating conditions of the rotor system were defined during the test. The acoustic data were properly referenced

An audit of PMTCT services at a regional hospital in South Africa

Prevention of mother-to-child transmission (PMTCT) is a major intervention world-wide in the fight against the HIV pandemic, and has resulted in markedly reduced rates of mother-to-child transmission rates in well-resourced countries. However, it seems that barriers to implementation of the programme exist at all levels of health care at all facilities providing maternal care.Aim: To conduct a clinical audit of the PMTCT programme at a regional hospital in Pietermaritzburg, KwaZulu-Natal, South Africa.Methods: Data was collected from an analysis of antenatal and medical records of women who attended antenatal care and delivered at the regional hospital between January and December 2007. Only pregnant women who attended antenatal care at this regional hospital and delivered in its facilities were selected for the study. Patients eligible for review were identified using the labour ward delivery log book.Results: Of the 499 records analysed, 479 women (96%) were offered testing, of which 473 accepted. Of those tested, 227 (48%) were HIV positive. Only 15 (6.1%) of the 246 who tested negative were re-tested. CD4 counts were done for only 159 (70%) of the 227 HIV-positive women. More importantly, only 134 (84.3%) received their results. Of the 227 HIV-positive women, only 131 (57.7%) were given 200 mg nevirapine at &ge; 28 weeks gestation (to take home and swallow once they had strong labour pains); 185 (81.5%) took nevirapine before delivery (i.e. the total number of both those that took NVP 2hrs) 143 (77.3%)took nevirapine > 2 hours before delivery and 84 (37%) took nevirapine < 2 hours before delivery. Of the babies, 208 (91.6%) were given nevirapinewithin 72 hours.Discussion: This audit shows that progress has been made in the implementation of PMTCT of HIV at this regional hospital by the high uptake of HIV testing; however, barriers to full implementation are caused by the lack of integration of testing, counselling and obtaining CD4 count results.Keywords: audit; PMTCT services; regional hospita

Phosphodiesterase-type 3 inhibitor potentiates cAMP generation and antiproliferative effects of treprostinil in pulmonary arterial smooth muscle cells from patients with pulmonary hypertension

The prostacyclin class of drugs are used in pulmonary arterial hypertension (PAH), a vascular proliferative disease. While evidence suggests agents improve survival, they eventually stop working. Thus ways are being sort to improve their clinical efficacy. We hypothesised that prostacyclin action could be enhanced by inhibition of phosphodiesterase type 3 (PDE3), a major regulator of cyclic AMP levels in the lung, whose activity appears increased in PAH [1]. Cell proliferation (assessed by cell number) and cyclic AMP assays were performed in pulmonary arterial smooth muscle cells derived from patients with idiopathic PAH (n=6). Treprostinil (1μM) significantly (p<0.001) increased cAMP by 7.0±0.6 fold (n=6) at 30 mins but not thereafter. In the presence of the relatively selective PDE3 inhibitor, cilostamide (1μM), treprostinil produced twice as much cAMP (13.1±0.8 compared to 25.0±2.7 pmol/mg protein, n=3), and levels remained significantly (p<0.05) elevated at 24 hr compared to analogue alone (10.8±1.8 versus 3.22±0.8, pmol/mg protein). Cilostamide (1 & 10μM) also suppressed growth induced by 10% FBS by 20%, as did treprostinil (1μM). The combination however, produced further growth suppression of 35% (p<0.05) and 47% (P<0.001) for low and high PDE inhibitor dose, respectively. In conclusion, PDE3 inhibition may help improve prostacyclin analogue action in IPAH by prolonging elevation in cAMP and enhancing the antiproliferative effects of these agents. Reference: 1. Murray F, et al. Am J Physiol 2007; 292: L294-L303. Supported by an unrestricted educational grant from United Therapeutics

Widespread Receptivity to Neuropeptide PDF throughout the Neuronal Circadian Clock Network of Drosophila Revealed by Real-Time Cyclic AMP Imaging

SummaryThe neuropeptide PDF is released by sixteen clock neurons in Drosophila and helps maintain circadian activity rhythms by coordinating a network of ∼150 neuronal clocks. Whether PDF acts directly on elements of this neural network remains unknown. We address this question by adapting Epac1-camps, a genetically encoded cAMP FRET sensor, for use in the living brain. We find that a subset of the PDF-expressing neurons respond to PDF with long-lasting cAMP increases and confirm that such responses require the PDF receptor. In contrast, an unrelated Drosophila neuropeptide, DH31, stimulates large cAMP increases in all PDF-expressing clock neurons. Thus, the network of ∼150 clock neurons displays widespread, though not uniform, PDF receptivity. This work introduces a sensitive means of measuring cAMP changes in a living brain with subcellular resolution. Specifically, it experimentally confirms the longstanding hypothesis that PDF is a direct modulator of most neurons in the Drosophila clock network

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

The Darlington and Northallerton Long Term Asthma Study: pulmonary function

BACKGROUND: The Darlington and Northallerton Asthma Study is an observational cohort study started in 1983. At that time little was published about long term outcome in asthma and the contribution of change in reversible disease or airway remodelling to any excess deterioration in function. The study design included regular review of overall and fixed function lung. We report the trends over fifteen years. METHODS: All asthmatics attending secondary care in 1983, 1988 and 1993 were recruited. Pulmonary function was recorded at attendance and potential best function estimated according to protocol. Rate of decline was calculated over each 5-year period and by linear regression analysis in those seen every time. The influence of potential explanatory variables on this decline was explored. RESULTS: 1724 satisfactory 5-year measurements were obtained in 912 subjects and in 200 subjects on all occasions. Overall rate of decline (ml/year (95%CI)) calculated from 5-year periods was FEV1 ♂41.0 (34.7–47.3), ♀28.9 (23.2–34.6) and best FVC ♂63.1 (55.1–71.2)ml/year, ♀45.8 (40.0–51.6).The principal association was with age. A dominant cubic factor suggested fluctuations in the rate of change in middle life with less rapid decline in youth and more rapid decline in the elderly. Rapid decline was possibly associated with short duration. Treatment step did not predict rate of deterioration. CONCLUSIONS: Function declined non-linearly and more rapidly than predicted from normal subjects. It reports for the first time a cubic relationship between age and pulmonary function. This should be taken into account when interpreting other articles reporting change in function over time

Tennis play intensity distribution and relation with aerobic fitness in competitive players

15 p.Los objetivos de este estudio fueron (1) describir la intensidad relativa del juego de tenis simulado en función del tiempo acumulado en tres zonas de intensidad metabólica y (2) determinar las relaciones entre esta distribución de intensidad de juego y la aptitud aeróbica de un grupo de jugadores competitivos. 20 jugadores masculinos de nivel avanzado a élite (ITN) realizaron una prueba de tenis de resistencia específica en el campo incremental hasta el agotamiento para determinar el consumo máximo de oxígeno (VO2max) y los umbrales de ventilación primero y segundo (VT1, VT2). Los parámetros de ventilación y de intercambio de gases se monitorizaron utilizando un analizador de gas portátil telemétrico (K4 b2, Cosmed, Roma, Italia). Dos semanas después, los participantes jugaron un juego de tenis simulado contra un oponente de nivel similar. Las zonas de intensidad (1: baja, 2: moderada y 3: alta) fueron delimitadas por los valores individuales de VO2 correspondientes a VT1 y VT2, y se expresaron como porcentaje del VO2 máximo y la frecuencia cardíaca. Cuando se expresó en relación con el VO 2 máx. El porcentaje de tiempo de juego en la zona 1 (77 ± 25%) fue significativamente mayor (p <0,001) que en la zona 2 (20 ± 21%) y la zona 3 (3 ± 5%). Se encontraron correlaciones positivas de moderadas a altas entre VT1, VT2 y VO2max, y el porcentaje del tiempo de juego transcurrido en la zona 1 (r = 0,68-0,75), así como las correlaciones inversas de bajas a altas entre las variables metabólicas y el porcentaje de tiempo empleado en las zonas 2 y 3 (r = -0.49–0.75). Los jugadores con mejor aptitud aeróbica juegan a intensidades relativamente más bajas. Concluimos que los jugadores pasaron más del 75% del tiempo en su zona de baja intensidad, con menos del 25% del tiempo dedicado a intensidades moderadas a altas. La aptitud aeróbica parece determinar la intensidad metabólica que los jugadores pueden mantener durante todo el juegoS

Sites of Circadian Clock Neuron Plasticity Mediate Sensory Integration and Entrainment

Networks of circadian timekeeping in the brain display marked daily changes in neuronal morphology. In Drosophila melanogaster, the striking daily structural remodeling of the dorsal medial termini of the small ventral lateral neurons has long been hypothesized to mediate endogenous circadian timekeeping. To test this model, we have specifically abrogated these sites of daily neuronal remodeling through the reprogramming of neural development and assessed the effects on circadian timekeeping and clock outputs. Remarkably, the loss of these sites has no measurable effects on endogenous circadian timekeeping or on any of the major output functions of the small ventral lateral neurons. Rather, their loss reduces sites of glutamatergic sensory neurotransmission that normally encodes naturalistic time cues from the environment. These results support an alternative model: structural plasticity in critical clock neurons is the basis for proper integration of light and temperature and gates sensory inputs into circadian clock neuron networks