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.

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.

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.

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.

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.

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.

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.

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.

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.

Risk behaviour and HIV prevalence in international travellers.

OBJECTIVE: To assess risk factors for infection and to determine HIV prevalence in a sample of international travellers. DESIGN: A cross-sectional survey of new patients attending a hospital outpatient clinic, and self-completion of an anonymous questionnaire on sexual behaviour prior to and during travel. Urine samples were tested for the presence of antibodies to HIV. SETTING: The Hospital for Tropical Diseases, London, UK. SUBJECTS: All new patients over a 6-month period. RESULTS: Of 782 people approached, 757 (97%) agreed to participate: 141 (18.6%) had had new sexual partners during their most recent trip abroad. Almost two-thirds of those having sex abroad did not use condoms on every occasion with a new partner, and 5.7% contracted a sexually transmitted disease (STD) during their most recent trip; 26% of men from World Health Organization Pattern I countries who had new sexual partners abroad paid for sex. Sixteen out of 731 (2.2%) participants were HIV-antibody-positive. HIV positivity was associated with being born in east, central or southern Africa, having symptoms of an STD since arriving in the United Kingdom and being treated for an STD since arrival. CONCLUSION: The rates of unsafe sex and payment for sex abroad reported by these international travellers indicate the potential for contracting and transmitting STD, including HIV, in both their foreign and domestic sexual partnerships. With the increasing HIV incidence in Asia (the most common destination for UK travellers after sub-Saharan Africa), the number of cases of HIV contracted abroad may rise in the future.

Identification and characterization of human tissue inhibitor of metalloproteinase-3 and detection of three additional metalloproteinase inhibitor activities in extracellular matrix.

We have identified and characterized a novel human tissue inhibitor of metalloproteinase (TIMP). It is found exclusively in the extracellular matrix of a large number of cultured human cells, including: primary embryonal kidney (293), neuroblastoma (SK-N-SH), normal whole embryo (FHs 173We), cervical carcinoma (HeLa S3), colon adenocarcinoma (Caco-2), ileocecal adenocarcinoma (HCT-8), fibrosarcomas (SW 684 and Hs 913T) and normal gingival fibroblasts (GF11 and 1292). It was not detected in the conditioned media from any of these cell lines. Its apparent molecular mass of 24-25 kDa, as determined by its migration on protease-substrate gels, is intermediate between TIMP-1 (28.5 kDa) and TIMP-2 (21 kDa). Like the latter two proteins, human TIMP-3 contains intrachain disulfide bonds and displays altered electrophoretic mobility in the presence of beta-mercaptoethanol. The N-terminal, amino acid sequence of the protein is identical to that of chicken TIMP-3 (ChIMP-3), and its amino acid composition is similar. The protein is not N-glycosylated, as determined by treatment with N-glycosidase-F. Finally, it is recognized by antisera raised against pure ChIMP-3 but not by anti-human TIMP-1 or anti-human TIMP-2 antibodies. Based on these properties, we propose that this protein is TIMP-3 and is the human counterpart of ChIMP-3 (Pavloff et al., J. Biol. Chem. 267: 17321-17326, 1992). Two additional inhibitors detected in the matrix of human cell lines, designated inhibitor of metalloproteinase (IMP)-a and IMP-b, migrate with apparent masses of 29 kDa and 30 kDa. Both are N-glycosylated. A fourth inhibitor activity, which is smaller in mass than TIMP-3 and is also pecifically located in the matrix, is detectable in some cell lines.

Murine tissue inhibitor of metalloproteinases-4 (Timp-4): cDNA isolation and expression in adult mouse tissues.

We have isolated cDNA clones corresponding to a new member of the murine tissue inhibitor of metalloproteinase (TIMP) family, designated Timp-4. The nucleotide sequence predicts a protein of 22,609 Da that contains the characteristic 12 cysteine TIMP signature. TIMP-4 is more closely related to TIMP-2 and TIMP-3 than to TIMP-1 (48%, 45% and 38% identity, respectively). Analysis of Timp-4 mRNA expression in adult mouse tissues indicated a 1.2 kb transcript in brain, heart, ovary and skeletal muscle. This pattern of expression distinguishes Timp-4 from other Timps, suggesting that the TIMP-4 protein may be an important tissue-specific regulator of extracellular matrix remodelling.

The sexual health of travelers.

Sex and travel do not infrequently coincide as pleasurable occupations. This articles explores the possible risks of unsafe sexual activity in a travel-related context, gives guidelines on how to decrease risks for both partners, and outlines how to manage the exposed or infected traveler on his or her return home. Both sexually transmitted infections and contraception are covered.

PIP: Travel and tourism are associated with an increased risk of sexually transmitted infections (STIs) and unwanted pregnancy. This article offers guidelines for health professionals on pre-travel counseling and outlines steps in the clinical management of returning travelers who have been exposed to STIs or pregnancy. The imperative for controlling STIs is particularly urgent now that an epidemiologic link between STIs and vulnerability to HIV infection has been established. Much can be done before a trip abroad in terms of prevention, including the provision of condoms and leaflets explaining the risks of unprotected sex while on holiday or a business trip. Patients should be questioned about their sexual behaviors before, during, and after travel and those who have taken sexual risks while traveling should be offered screening for STIs. The STI-related conditions addressed in this article include vaginal discharge, lower abdominal pain, urethral discharge, scrotal pain, genital ulcer disease, inguinal bubo, and genital warts. Recommended treatment regimens for the most prevalent reproductive tract infections are outlined.

p53-dependent activation of the mouse MCK gene promoter: identification of a novel p53-responsive sequence and evidence for cooperation between distinct p53 binding sites.

Transcriptional activation by p53 is dependent on the presence of a specific p53 binding site within control sequences of the target gene. One such target gene is the mouse muscle-specific creatine kinase (MCK) gene, which contains a p53 binding site between promoter residues -3182 and -3133 relative to the transcription start site. This DNA sequence is reported to be sufficient to confer p53-dependent activation on the MCK promoter. In contrast to this finding, evidence from promoter deletion studies suggests that sequences in the MCK promoter other than this p53 binding site also permit p53-dependent activation. To investigate this possibility, we have further examined sequences in the MCK promoter required for transcriptional activation by mouse p53. We report here identification of a second p53-responsive sequence within the MCK promoter. This novel sequence is situated between residues -177 and -81, and can confer p53-dependent, position- and orientation-independent activation on a heterologous promoter. Moreover, this sequence can specifically bind mouse and human p53. By promoter deletion studies, we provide evidence that these two elements cooperate to provide high-level, p53-dependent activation of the MCK promoter.

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.

An overview of the global epidemiology of HIV/AIDS.

Over 5 million people continue to be newly infected with HIV every year, despite advances in understanding the factors that drive the epidemics. It is apparent that control of the HIV epidemics has often proved difficult due to the complex web of behavioural, biological, social and structural vulnerabilities to infection. In this paper we discuss the epidemiology and control of HIV in sub-Saharan Africa, and draw parallels with the emerging epidemic in South and South-East Asia. Prevalence of infection in sub-Saharan Africa has continued to increase overall, but a few countries have successfully reduced national infection rates by employing an integrated, multisectoral control strategy. Prevention of similar devastating epidemics in other regions will rely upon an openness in recognizing risk and upon a concerted multisectoral approach to reduction of risk of risk at the individual level and level and vulnerability at the societal and structural levels.

Variation of retention volume with molecular weight of polyethylene glycol and with carbon number of n-alkanols.

Analysis of McReynolds' data for n-alkanols on polyethylene glycols of various molecular weights shows a continuous variation in retention properties up to molecular weights greater than 6000 and probably greater than 20,000. It is concluded that polyethylene glycol used as a "standard" stationary phase should have either very high or closely controlled molecular weight. The relation between log Vg and carbon number of the alkanol is nonlinear at C4 and below with negative deviations around 10% for C2 and C3 and a positive deviation of 25% for C1.

Hepatitis B infection in Bangladeshi mothers and infants.

In order to estimate the relative importance of perinatal transmission of hepatitis B in rural Bangladesh a cross-sectional study was carried out. Paired-serum samples of infants aged 2-8 months old, a group of new born, and their mothers were tested for hepatitis B markers using a commercial ELISA test kit. In total, 107 (32.4%) positive for HBcAg, 18 (5.4%) for HBsAg, and 4 (1.2%) for HbeAg. Of the infants, 35 (10.5%) positive for HBcAg, 1 (0.3%) for HBsAg, and none for HBeAg. Of the 18 HBsAg positive mothers, 4 (22%) were HBeAg positive. All 14 children of mothers who were HBeAg negative were negative for HBsAg. Only one out of four (25%) of children of HBeAg positive mothers were HBsAg carriers (8 months old), and in three children transmission did not occur (two 8 months, one 6 months old). This survey indicates that hepatitis B is prevalent in rural Bangladesh and that the perinatal transmission mode may be relatively low.