The oxygen uptake efficiency slope in adults with CHD: group validity.

The maximal oxygen uptake (V02 max) is a well-validated measure of cardiorespiratory function that is calculated during a maximal cardiopulmonary exercise test. V02 max enables physicians to objectively assess cardiopulmonary function to aid in decision-making for patients with CHD. A significant proportion of these patients however are unable to achieve a maximal exercise test, and as such, there is a need for reliable submaximal predictors of cardiorespiratory reserve.The oxygen uptake efficiency slope represents a measure of how effectively oxygen is extracted from the lungs and taken into the body and can be calculated from a submaximal exercise test. Its reliability as a predictor of cardiorespiratory reserve has been validated in various patient populations, but there is limited evidence for its validity in adult patients with CHD.Retrospective analysis of cardiopulmonary exercise test data in 238 consecutive patients with CHD who completed a maximal cardiopulmonary exercise test at our tertiary cardiology centre demonstrated a strong correlation between peak V02 and the oxygen uptake efficiency slope (0.936). A strong correlation with peak V02 was also demonstrated when oxygen uptake efficiency slope was calculated at ventilatory anaerobic threshold (OUESVAT), 75% (OUES75), and 90% (OUES90) of the test (0.833, 0.905, 0.927 respectively).In adult patients with CHD who are unable to complete a maximal cardiopulmonary exercise test, the oxygen uptake efficiency slope is a reliable indicator of cardiopulmonary fitness which correlates strongly with peak V02 at or beyond the ventilatory anaerobic threshold. Further research is required to validate the findings in patients with less common anatomies and to assess the relationship between the oxygen uptake efficiency slope and mortality.

Influence of spatial-intensity contrast in ultraintense laser-plasma interactions.

Increasing the intensity to which high power laser pulses are focused has opened up new research possibilities, including promising new approaches to particle acceleration and phenomena such as high field quantum electrodynamics. Whilst the intensity achievable with a laser pulse of a given power can be increased via tighter focusing, the focal spot profile also plays an important role in the interaction physics. Here we show that the spatial-intensity distribution, and specifically the ratio of the intensity in the peak of the laser focal spot to the halo surrounding it, is important in the interaction of ultraintense laser pulses with solid targets. By comparing proton acceleration measurements from foil targets irradiated with by a near-diffraction-limited wavelength scale focal spot and larger F-number focusing, we find that this spatial-intensity contrast parameter strongly influences laser energy coupling to fast electrons. We find that for multi-petawatt pulses, spatial-intensity contrast is potentially as important as temporal-intensity contrast.

High order mode structure of intense light fields generated via a laser-driven relativistic plasma aperture.

The spatio-temporal and polarisation properties of intense light is important in wide-ranging topics at the forefront of extreme light-matter interactions, including ultrafast laser-driven particle acceleration, attosecond pulse generation, plasma photonics, high-field physics and laboratory astrophysics. Here, we experimentally demonstrate modifications to the polarisation and temporal properties of intense light measured at the rear of an ultrathin target foil irradiated by a relativistically intense laser pulse. The changes are shown to result from a superposition of coherent radiation, generated by a directly accelerated bipolar electron distribution, and the light transmitted due to the onset of relativistic self-induced transparency. Simulations show that the generated light has a high-order transverse electromagnetic mode structure in both the first and second laser harmonics that can evolve on intra-pulse time-scales. The mode structure and polarisation state vary with the interaction parameters, opening up the possibility of developing this approach to achieve dynamic control of structured light fields at ultrahigh intensities.

Near-100 MeV protons via a laser-driven transparency-enhanced hybrid acceleration scheme.

The range of potential applications of compact laser-plasma ion sources motivates the development of new acceleration schemes to increase achievable ion energies and conversion efficiencies. Whilst the evolving nature of laser-plasma interactions can limit the effectiveness of individual acceleration mechanisms, it can also enable the development of hybrid schemes, allowing additional degrees of control on the properties of the resulting ion beam. Here we report on an experimental demonstration of efficient proton acceleration to energies exceeding 94 MeV via a hybrid scheme of radiation pressure-sheath acceleration in an ultrathin foil irradiated by a linearly polarised laser pulse. This occurs via a double-peaked electrostatic field structure, which, at an optimum foil thickness, is significantly enhanced by relativistic transparency and an associated jet of super-thermal electrons. The range of parameters over which this hybrid scenario occurs is discussed and implications for ion acceleration driven by next-generation, multi-petawatt laser facilities are explored.

Brief sexuality communication--a behavioural intervention to advance sexually transmitted infection/HIV prevention: a systematic review.

BACKGROUND: Throughout the last decade substantial research has been undertaken to develop evidence-based behaviour change interventions for sexual health promotion. Primary care could provide an opportunistic entry for brief sexual health communication. OBJECTIVES: We conducted a systematic review to explore opportunistic sexual and reproductive health services for sexual health communication delivered at primary health care level. SEARCH STRATEGY: We searched for studies on PubMed, ProQuest, CINAHL, Jstor, Scopus/Science Direct, Cochrane database of systematic reviews, EBSCO, CINAHL, PsychoInfo, and Web of Knowledge. Both published and unpublished articles were reviewed. SELECTION CRITERIA: All randomised controlled trials and controlled clinical trials were included. Participants of all ages, from adolescence onwards were included. Brief (10-60 minutes) interventions including some aspect of communication on sexual health issues were included. DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers independently using a standardised form. Interventions differed from each other, hence meta-analysis was not performed, and results are presented individually. MAIN RESULTS: A total of 247 articles were selected for full-text evaluation, 31 of which were included. Sexually transmitted infections (STIs)/HIV were less often reported in the intervention group compared with the control group. Condom use was higher in most studies in the intervention group. Numbers of sexual partners and unprotected sexual intercourse were lower in the intervention groups. CONCLUSIONS: There is evidence that brief counselling interventions have some effect in the reduction and prevention of STIs/HIV. Some questions could not be answered, such as the effect over time and in different settings and population groups.

Compact laser accelerators for X-ray phase-contrast imaging.

Advances in X-ray imaging techniques have been driven by advances in novel X-ray sources. The latest fourth-generation X-ray sources can boast large photon fluxes at unprecedented brightness. However, the large size of these facilities means that these sources are not available for everyday applications. With advances in laser plasma acceleration, electron beams can now be generated at energies comparable to those used in light sources, but in university-sized laboratories. By making use of the strong transverse focusing of plasma accelerators, bright sources of betatron radiation have been produced. Here, we demonstrate phase-contrast imaging of a biological sample for the first time by radiation generated by GeV electron beams produced by a laser accelerator. The work was performed using a greater than 300 TW laser, which allowed the energy of the synchrotron source to be extended to the 10-100 keV range.

Near-GeV acceleration of electrons by a nonlinear plasma wave driven by a self-guided laser pulse.

The acceleration of electrons to approximately 0.8 GeV has been observed in a self-injecting laser wakefield accelerator driven at a plasma density of 5.5x10(18) cm(-3) by a 10 J, 55 fs, 800 nm laser pulse in the blowout regime. The laser pulse is found to be self-guided for 1 cm (>10zR), by measurement of a single filament containing >30% of the initial laser energy at this distance. Three-dimensional particle in cell simulations show that the intensity within the guided filament is amplified beyond its initial focused value to a normalized vector potential of a0>6, thus driving a highly nonlinear plasma wave.

Prevalence of HIV, HCV and sexually transmitted infections among injecting drug users in Rawalpindi and Abbottabad, Pakistan: evidence for an emerging injection-related HIV epidemic.

OBJECTIVES: To measure the prevalence of hepatitis C virus (HCV), HIV and sexually transmitted infections (STI) among injecting drug users (IDUs) in Rawalpindi and Abbottabad and to examine risk factors associated with HIV and HCV. METHODS: Two cross-sectional surveys were performed of community-recruited IDUs with collection of clinical specimens for testing of HCV, HIV and other STIs. Behavioural data were collected through interviewer-administered questionnaires. Characteristics and risk behaviours were compared across cities. Univariate and multivariate analyses explored risk factors associated with HIV and HCV. RESULTS: The prevalence of HIV was 2.6% (95% CI 0.83% to 4.5%) in Rawalpindi (n = 302) and zero in Abbottabad (n = 102). The prevalence of HCV was significantly higher in Rawalpindi at 17.3% (95% CI 13.0% to 21.6%) than in Abbottabad at 8% (95% CI 2.6% to 13.4%). The prevalence of other STIs was low in both cities, with <2% of participants having current gonorrhoea or Chlamydia and <3% with active syphilis. Injecting risk behaviours were greater in Rawalpindi. An increased risk of HCV was associated with using informal sources as a main source of new needles/syringes (OR 2.8, 95% CI 1.3 to 6.0) compared with pharmacies and a history of drug treatment (OR 3.7, 95% CI 0.9 to 11.6). Reporting symptoms of an STI was associated with decreased odds of HIV in Rawalpindi (OR 0.02, 95% CI 0.03 to 0.9). CONCLUSIONS: The findings suggest recent transmission of HIV and HCV and point to the urgent need for the provision of clean needles/syringes to IDUs and a review of how needles/syringes are currently provided via healthcare establishments.

Modelling the transmission of HIV and HCV among injecting drug users in Rawalpindi, a low HCV prevalence setting in Pakistan.

BACKGROUND: In 2007, a survey in Rawalpindi found the prevalence of hepatitis C virus (HCV) in injecting drug users (IDUs) to be low (17%), despite widespread needle/syringe sharing. This analysis uses modelling to explore hypotheses for the low prevalence of HCV to project the future HIV/HCV epidemic and to estimate the impact of a generic intervention. METHODS: An HIV/HCV transmission model was developed and parameterized using data from Rawalpindi. By incorporating different assumptions about the relative frequency/importance of needle/syringe sharing events among "strangers" and people they have shared with before, and undertaking extensive uncertainty analyses to fit the model for each scenario, the validity of different hypotheses for the low HCV prevalence was determined. Model fits were used to project the future HIV/HCV epidemic and the impact of reducing needle/syringe sharing among different IDU subgroups. RESULTS: The model projections suggest that the low HCV prevalence in Rawalpindi is probably due to most HIV/HCV transmissions occurring in a small IDU subgroup that shares needles/syringes frequently with strangers, with most needle/syringe sharing incidents being low risk. Projections suggest that the prevalence of HIV in IDUs will increase to 5-12% by 2015, and the prevalence of HCV will increase if HIV increases HCV transmission. Moderate reductions in needle/syringe sharing (>40%) could reduce the number of HCV/HIV infections (approximately 45%) if all IDUs are reached, although less impact is achieved if high-risk IDUs are not reached. CONCLUSIONS: Despite many needle/syringe sharing events possibly being low risk in Rawalpindi, the model projects that the prevalence of HIV/HCV in IDUs is likely to increase. This highlights the importance of intervening in this low prevalence setting.

Protecting the unprotected: mixed-method research on drug use, sex work and rights in Pakistan's fight against HIV/AIDS.

OBJECTIVES: To investigate the nature and extent of human rights abuses against three vulnerable groups (injecting drug users (IDUs) and male and female sex workers), to understand the social and sexual linkages between them and to examine how protecting their rights could enhance the impact of HIV prevention policies. METHODS: In-depth interviews were carried out with 38 high-risk respondents (IDUs and female, male and transgender sex workers) and a bio-behavioural survey was performed of 813 IDU/sex worker respondents in Rawalpindi. RESULTS: People in all vulnerable groups interacted both sexually and socially. All groups experienced human rights abuses by state and non-state actors which increased their HIV risk. Non-state actors, including relations and sex worker clients, are responsible for verbal, physical and sexual violence. State actors (particularly police) perpetrate harassment, exploitation and abuse of all vulnerable groups with impunity. Health service providers fail to provide adequate services for vulnerable groups. CONCLUSIONS: High levels of discrimination and abuse of human dignity of all groups studied were revealed. This violates their physical and mental integrity and also leads to an increased risk of HIV. The sexual and social interactions between groups mean that human rights abuses experienced by one high-risk group can increase the risk of HIV both for them and other groups. The protection of human rights needs to become an integral part of a multisector response to the risk of HIV/AIDS by state and non-state agencies. The Government of Pakistan should work at both legal and programme levels to protect the rights of, and minimise discrimination against, groups vulnerable to HIV in order to reduce the potential for the spread of HIV before the epidemic takes hold.

Political feasibility of scaling-up five evidence-informed HIV interventions in Pakistan: a policy analysis.

BACKGROUND: Drawing on policy theories, an assessment was made of the perceived political feasibility of scaling-up five evidence-based interventions to curb Pakistan's HIV epidemic: needle and syringe exchange programmes; targeted behaviour change communication; sexual health care for male and transgender sex workers; sexual and reproductive health care for female sex workers; and promoting and protecting the rights of those at greatest risk. METHOD: A questionnaire was emailed to 40 stakeholders and completed by 22. They expressed their level of agreement with 15 statements for each intervention (related to variables associated with policy success). Semi-structured interviews were conducted with 12 respondents. RESULTS: The interventions represent considerable change from the status quo, but are perceived to respond to widely acknowledged problems. These perceptions, held by the HIV policy elite, need to be set in the context of the prevailing view that the AIDS response is not warranted given the small and concentrated nature of the epidemic and that the interventions do not resonate closely with values held by society. The interventions were perceived to be evidence-based, supported by at least one donor and subject to little resistance from frontline staff as they will be implemented by contracted non-government organisations. The results were mixed in terms of other factors determining political feasibility, including the extent to which interventions are easy to explain, exhibit simple technical features, require few additional funds, are supported and not opposed by powerful stakeholders. CONCLUSION: The interventions stand a good chance of being implemented although they depend on donor support. The prospects for scaling them would be improved by ongoing policy analysis and strengthening of domestic constituencies among the target groups.

HIV and other sexually transmitted infections among men, transgenders and women selling sex in two cities in Pakistan: a cross-sectional prevalence survey.

OBJECTIVES: The extent and possibilities of spread of the HIV epidemic are not fully understood in Pakistan. A survey was conducted among men, women and transgender populations selling sex in Rawalpindi (Punjab) and Abbottabad (North West Frontier Province) in order to inform evidence-based programme planning. METHODS: A cross-sectional survey was performed with participants recruited through respondent-driven sampling. Male and transgender sex workers were analysed in three gender groups; women were analysed as one group. Behavioural surveys were conducted and clinical specimens collected. Laboratory tests looked for evidence of acute infection (gonorrhoea, Chlamydia, syphilis, Trichomonas) and infection over the lifetime (HIV, herpes simplex virus-2, syphilis). Predictors of infection were explored using univariable and multivariable logistic regression. RESULTS: The prevalence of HIV was low in 917 male and transgender sex workers and absent in 533 female sex workers in the study. High levels of current sexually transmitted infections were found, predominantly among transgender sex workers. Risk behaviours were common and knowledge of HIV was extremely low. Multivariable analysis found a large number of factors associated with higher levels of infection, including experience of forced first sex. Protection against risk was low, but those sex workers who reported using condoms at last sex had lower rates of infection. CONCLUSIONS: The HIV epidemic is currently in its early stages among people who sell sex, but there may be potential for a much greater spread given the levels of other sexually transmitted infections found and the concomitant low levels of both protective knowledge and risk-reducing behaviours. Action is needed now to avert an epidemic. Framing interventions by upholding the recognition and protection of human rights is vital.

Herpes simplex virus type 2: epidemiology and management options in developing countries.

Genital herpes simplex virus type 2 (HSV2) is highly prevalent worldwide and an increasingly important cause of genital ulcer disease (GUD). Continued HSV2 transmission is facilitated by the large number of undiagnosed cases, the frequency of atypical disease and the occurrence of asymptomatic shedding. The lack of easy, affordable diagnostic methods and specific antiviral treatment in countries with low and middle income is of great concern, given the ability of GUD to enhance HIV transmission and acquisition. With rising HSV2 prevalence contributing to an increase in the proportion of GUD attributed to genital herpes in high-HIV prevalence settings, a safe and effective HSV vaccine is urgently needed. Meanwhile, multifaceted interventions are required to improve recognition of genital herpes, to prevent its spread and also to prevent its potential to promote HIV transmission in developing countries.

Herpes simplex virus type 2: epidemiology and management options in developing countries.

Genital herpes simplex virus type 2 (HSV2) is highly prevalent worldwide and an increasingly important cause of genital ulcer disease (GUD). Continued HSV2 transmission is facilitated by the large number of undiagnosed cases, the frequency of atypical disease and the occurrence of asymptomatic shedding. The lack of easy, affordable diagnostic methods and specific antiviral treatment in countries with low and middle income is of great concern, given the ability of GUD to enhance HIV transmission and acquisition. With rising HSV2 prevalence contributing to an increase in the proportion of GUD attributed to genital herpes in high-HIV prevalence settings, a safe and effective HSV vaccine is urgently needed. Meanwhile, multifaceted interventions are required to improve recognition of genital herpes, to prevent its spread and also to prevent its potential to promote HIV transmission in developing countries.

Radiological characterisation of photon radiation from ultra-high-intensity laser-plasma and nuclear interactions.

With the increasing number of multi-terawatt (10(12) W) and petawatt (10(15) W) laser interaction facilities being built, the need for a detailed understanding of the potential radiological hazards is required and their impact on personnel is of major concern. Experiments at a number of facilities are being undertaken to achieve this aim. This paper describes the recent work completed on the Vulcan petawatt laser system at the CCLRC Rutherford Appleton Laboratory, where photon doses of up to 43 mSv at 1 m per shot have been measured during commissioning studies. It also overviews the shielding in place on the facility in order to comply with the Ionising Radiation Regulations 1999 (IRR99), maintaining a dose to personnel of less than 1 mSv yr(-1) and as low as reasonably practicable (ALARP).

Microreactors as new tools for drug discovery and development.

In common with other producers of fine chemicals, the pharmaceutical industry can deploy flow microreactors to provide a more flexible production regime than is achievable with large-scale batch reactors. With monitoring of output flow, microreactors can be adjusted exquisitely to give enhanced and inherently safer protocols. Bulk production can be achieved through long run times or parallel reactors. However, microreactors can also be used advantageously in pharmaceutical R&D in other ways. This paper describes their use in the creation of a tool for rapid discovery and optimisation of leads to new drugs. Here microreactors are used to create an integrated micro-scaled chemical synthesis and bioassay system able to conduct fast-cycling iterative searches of diverse chemical space as an enhanced method for identifying and optimising novel lead chemotypes. The use of a microreactor to provide point-of-use access to PET ligands is also described. This significant down-scaling and acceleration of the synthesis of potent but short-lived biomarkers of disease could provide a means of significantly shortening the time and resources required to achieve a drug approval.

Sexually transmitted infections prevalence rates in slum communities of Dhaka, Bangladesh.

The study objective was to estimate the prevalence of selected sexually transmitted infections (STIs) and associated factors among Dhaka slum dwellers. Blood and urine specimens were collected from 1534 men and women. Participants in this cross-sectional study responded to a questionnaire, providing socioeconomic data, symptomatology and treatment-seeking behaviour. Specimens were tested for syphilis, hepatitis B (HBsAg), Neisseria gonorrhoeae, Chlamydia trachomatis, and HIV. Serologic evidence of syphilis infection was found in 6.0% of respondents, HBsAg in 3.8%. Prevalence rates of gonorrhoea and chlamydia were 1.7% and <1%, respectively. No HIV infections were found. Men were more than twice as likely as women to be infected with syphilis or HBsAg carriers. Behaviours facilitating STI transmission were common among men. Syphilis infection is prevalent enough to warrant the initiation of screening programmes in this population. The prevalence rate of hepatitis B carriage suggests that this population would benefit from universal vaccination against hepatitis B.

Diverse realities: sexually transmitted infections and HIV in India.

There are many features that make India a vulnerable country as far as a sexually transmitted infection (STI)/HIV epidemic is concerned. These include the lack of a strong evidence base on which to formulate decision making, a pluralistic and often unregulated health sector, and a highly vulnerable population. Nonetheless, India has shown strong commitment to other areas of a comprehensive reproductive health care programme, and may be able to do so in the field of STI/HIV control. Vast numbers of people in India are severely disadvantaged in terms of income, education, power structures, and gender. Addressing these basic issues of human rights lies at the core of achieving better health outcomes.

Large-amplitude plasma wave generation with a high-intensity short-pulse beat wave.

A short-pulse laser beat wave scheme for advanced particle accelerator applications is examined. A short, intense (3-ps, >10(18)-W cm(-2)) two-frequency laser pulse is produced by use of a modified chirped-pulse amplification scheme and is shown to produce relativistic plasma waves during interactions with low-density plasmas. The generation of plasma waves was observed by measurement of forward Raman scattering. Resonance was found to occur at an electron density many times that expected, owing to ponderomotive displacement of plasma within the focal region.

Local production of anti-vibrio cholerae mucosal antibody in reproductive tract tissues after cholera.

To investigate whether intestinal presentation of an antigen by Vibrio cholerae, a noninvasive organism, could induce an anatomically distant mucosal immune response in reproductive tract tissues, the endocervical immune responses of women in Bangladesh were evaluated after cholera. Endocervical secretions were analyzed for secretory IgA (sIgA) antibody against the B subunit of cholera toxin (CtxB) in 9 women with cholera and 8 women with diarrhea caused by neither V. cholerae nor heat labile enterotoxin-producing Escherichia coli. Women infected with V. cholerae developed significant sIgA anti-CtxB responses in endocervical samples (P< or =.02). Antibody subtype analysis of endocervical IgA was consistent with local mucosal production (P< or =.001). Women with cholera did not develop sIgA anti-CtxB responses in serum. The ability to generate specific mucosal immune responses in reproductive tract tissues after intestinal presentation of antigen could facilitate development of vaccines effective against reproductive tract pathogens.