Voluntary Counselling, HIV Testing and Sexual Behaviour Among Patients with Tuberculosis in a Rural District of Malawi.

OBJECTIVES: A study was conducted in new patients registered with tuberculosis (TB) in a rural district of Malawi in order to 1) verify the acceptability of voluntary counselling and testing for human immunodeficiency virus (HIV) infection; 2) describe sexual behaviour and condom use; and 3) identify socio-demographic and behavioural risk factors associated with 'no condom use'. DESIGN: Cross-sectional study. METHODS: Consecutive patients diagnosed with TB between January and December 2000 were offered voluntary counselling and HIV testing (VCT) and were subsequently interviewed. RESULTS: There were 1,049 new TB patients enrolled in the study. Of these, 1,007 (96%) were pre-test counselled, 955 (91%) underwent HIV testing and 912 (87%) were post-test counselled; 43 (4%) patients refused HIV testing. The overall HIV infection rate was 77%. Of all HIV-positive TB patients, 691 (94%) were put on cotrimoxazole. There were 479 (49%) TB patients who reported sexual encounters, of whom only 6% always used condoms. Unprotected sex was associated with having TB symptoms for over 1 month, having had less than 8 years of school education, being single, divorced or widowed or having sex with the same partner. CONCLUSIONS: Offering VCT to TB patients in this setting has a high acceptance rate and provides an opportunity to strengthen and integrate TB and HIV programmes

A spatially and temporally localized sub-laser-cycle electron source

We present an experimental and numerical study of electron emission from a sharp tungsten tip triggered by sub-8 femtosecond low power laser pulses. This process is non-linear in the laser electric field, and the non-linearity can be tuned via the DC voltage applied to the tip. Numerical simulations of this system show that electron emission takes place within less than one optical period of the exciting laser pulse, so that an 8 fsec 800 nm laser pulse is capable of producing a single electron pulse of less than 1 fsec duration. Furthermore, we find that the carrier-envelope phase dependence of the emission process is smaller than 0.1% for an 8 fsec pulse but is steeply increasing with decreasing laser pulse duration.Comment: 4 pages, 5 figure

Multidisciplinary treatment for chronic pain: a systematic review of interventions and outcomes

Objectives. To provide an overview of the effectiveness of multidisciplinary treatments of chronic pain and investigate about their differential effects on outcome in various pain conditions and of different multidisciplinary treatments, settings or durations. Methods. In this article, the authors performed a systematic review of all currently available randomized controlled trials (RCTs) fulfilling the inclusion criteria, by using a recently developed rating system aimed to assess the strength of evidence with regard to the methodological quality of the trials. Results. Compared with other non-disciplinary treatments, moderate evidence of higher effectiveness for multidisciplinary interventions was shown. In contrast to no treatment or standard medical treatment, strong evidence was detected in favour of multidisciplinary treatments. The evidence that comprehensive inpatient programmes were more beneficial that outpatient programmes was moderate. Fibromyalgia and chronic back pain patients tended to profit more substantially than patients with diverse origins or chronic pain diagnoses. No evidence was found that treatment variables, such as duration or programme components, were influential for the success of the intervention. Conclusion. A standard of multidisciplinary programmes should be internationally established to guarantee generally good outcomes in the treatment of chronic pain. Our results highlight the lack of quality of design, execution or reporting of many of the RCTs included in this article. Future studies should more specifically focus on differential effects of treatment components and patient variables, allowing the identification of subgroups, which most probably would profit from multidisciplinary pain programme

Voluntary Counselling, HIV Testing and Adjunctive Cotrimoxazole Reduces Mortality in Tuberculosis Patients in Thyolo, Malawi.

OBJECTIVES: To assess the feasibility and effectiveness of voluntary counselling, HIV testing and adjunctive cotrimoxazole in reducing mortality in a cohort of tuberculosis (TB) patients registered under routine programme conditions in a rural district of Malawi. DESIGN: 'Before' and 'after' cohort study using historical controls. METHODS: Between 1 July 1999 and 30 June 2000 all TB patients were started on standardized anti-TB treatment, and offered voluntary counselling and HIV testing (VCT). Those found to be HIV-positive were offered cotrimoxazole at a dose of 480 mg twice daily, provided there were no contraindications. Side-effects were monitored clinically. End-of-treatment outcomes in this cohort (intervention group) were compared with a cohort registered between 1 July 1998 and 30 June 1999 in whom VCT and cotrimoxazole was not offered (control group). FINDINGS: A total of 1986 patients was registered in the study: 1061 in the intervention group and 925 in the control cohort. In the intervention group, 1019 (96%) patients were counselled pre-test, 964 (91%) underwent HIV testing and 938 (88%) were counselled post-test. The overall HIV-seroprevalence rate was 77%. A total of 693 patients were given cotrimoxazole of whom 14 (2%) manifested minor dermatological reactions. The adjusted relative risk of death in the intervention group compared with the control group was 0.81 (P < 0.001). The number needed to treat with VCT and adjunctive cotrimoxazole to prevent one death during anti-TB treatment was 12.5. INTERPRETATION: This study shows that VCT and adjunctive cotrimoxazole is feasible, safe and reduces mortality rates in TB patients under routine programme conditions

The impact of latent CMV infection on NK-cell mobilization and expression of KLRG1 and CD57 in response to acute exercise.

Natural killer (NK) cells are cytotoxic effectors of the innate immune system that are able to distinguish healthy autologous cells from tumors and virally infected cells. NK-cells kill the targeted cells by releasing cytotoxic proteins, a process that is governed by inhibitory surface receptors, such as KLRG1. Additionally, activated NK-cells are able to proliferate in response to immunological stimuli, a process that is inhibited in NK-cells expressing the senescence marker CD57. Acute bouts of exercise are known to mobilize NK cells into the blood compartment, which could alter immunity; however, whether or not exercise alters NK-cell KLRG1 and CD57 expression has not been fully elucidated. Furthermore, as latent CMV infection is associated with an increased frequency of inhibitory NK cells, it is not known if CMV status influences NK-cell mobilization in response to acute exercise. PURPOSE: To examine the impact of latent CMV infection on the mobilization of NK-cells and their expression of KLRG1 and CD57 in response to acute exercise. METHODS: Otherwise healthy CMV seropositive (CMV+) and CMV seronegative (CMV-) males (age 23-35 years) completed a 30-min cycling protocol at 85% of maximum power. Lymphocytes isolated from whole blood before, immediately after, and one hour after exercise were surface-stained with monoclonal antibodies against CD3, CD56, KLRG1 and CD57 and analyzed by 4-color flow cytometry. RESULTS: Preliminary analysis of the data show a prodigious increase in the number of CD56 dim (mature, highly cytotoxic subset) NK-cells immediately after exercise in all subjects, which subsequently fell below pre-exercise values 1 hour later. In CMV- subjects, the proportion of CD56 bright (immature, mildly cytotoxic) NK cells was considerably higher 1 hour post-exercise than before exercise, but the number of cells changed very little suggesting that the increased proportion was due merely to the egress of CD56 dim NK cells. Interestingly, CMV seropositivity was associated with a near complete absence of CD56 bright NK cells that was unaffected by exercise. Neither exercise nor CMV status influenced the proportion of NK-cells expressing KLRG1 or CD57. CONCLUSION: Preliminary analysis of this data indicates that acute exercise preferentially mobilizes CD56 dim NK cells without altering KLRG1 and CD57 expression. Latent CMV infection is associated with a lowered proportion of CD56 bright NK-cells; however, the NK-cell response to exercise was not influenced by CMV status. Future work will examine the role of aging on NK-cell response to exercise and CMV status

The Impact of Latent Herpesvirus Infections on the Mobilization of Recent Thymic Emigrants and Extrathymic T-cells in Response to Acute Aerobic Exercise in Man

T-cells typically mature in the thymus gland, which eventually succumbs to age-related atrophy, resulting in a decreased naïve T-cell repertoire in middle to later years. Aged individuals and those with persistently reactivating herpesvirus infections have an increased reliance on the extrathymic maturation of T-cells due to the shrinking effects that age and latent viral infection has on the naïve T-cell repertoire. Acute bouts of aerobic exercise are known to mobilize T-cells that exhibit both a naïve and late-stage differentiation phenotype into the blood compartment; however, it is not known if recent thymic emigrants (RTE) or extrathymic T-cells contribute to the lymphocytosis associated with exercise. PURPOSE: To examine the impact of latent cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection on the mobilization of RTE and extrathymic T-cells in response to acute exercise. METHODS: Otherwise healthy CMV or EBV seropositive (CMV+ or EBV+) and CMV or EBV seronegative (CMV- or EBV-) males (age 23-35y) completed a 30-min cycling protocol at 85% of maximum power. Lymphocytes isolated from whole blood before, immediately after, and one hour after exercise were surface stained with monoclonal antibodies to identify phenotypes of RTE (CD103+/CD62L-) and extrathymic T-cells believed to mature in the liver (CD3+/CD25-/CD122+) and the epithelium of the small intestine (CD3+/CD4-/CD8-; TCRγδ+/ CD8αα+; CD3-/CD2+/CD7+). Cell populations were analyzed by flow cytometry and antibodies against CMV and EBV were determined in serum by ELISA. RESULTS: Preliminary analyses show that the proportion of RTE among the total CD3+/CD4+ or CD3+/CD8+ T-cell subsets did not change immediately after exercise, but was elevated above baseline 1h later due to the preferential egress of late stage differentiated T-cells. Neither CMV nor EBV status influenced the proportions of RTE in blood in response to exercise. T-cells mainly found in intestinal mucosa (i.e. CD3+/CD4-/CD8- and CD3-/CD2+/CD7+) were found to increase in blood immediately after exercise; an effect that appeared to be more pronounced in EBV but not CMV-infected subjects. CONCLUSION: An acute bout of aerobic exercise elicits the mobilization of T-cells exhibiting phenotype characteristics of extrathymically matured T-cells, suggesting that extrathymic T-cell mobilization contributes to the lymphocytosis associated with acute exercise. This effect appears to be amplified in subjects carrying a latent EBV but not CMV infection. Future research should attempt to establish the impact of long-term exercise and latent herpesvirus infections on the frequency of RTE and extrathymic T-cells in the aged, as this could have significant implications for age-associated immune dysfunction

The Impact of Long Duration Spaceflight on Plasma Antimicrobial Proteins

Introduction: Robust immunity is essential for further human exploration of the solar system beyond Earth’s orbit. Spaceflight has been associated with immune perturbations and latent viral reactivation. However, logistical constraints have restricted many of these studies to simple pre- and post-flight measures, which are greatly confounded by the stressors associated with launch, landing and re-adaptation to the 1G environment. More in-flight immune data are required particularly during long-duration (3-6 months) spaceflight missions. This study examined the effects of spaceflight on plasma antimicrobial proteins (AMPs) and reactivation of latent herpesviruses. Methods: Plasma, saliva and urine samples were obtained from 20 crewmembers who spent ~6-months on the International Space Station (ISS). Samples were collected 180 and 45-days before launch, in-flight (at ‘early, ‘mid’ and ‘late’ stages of the mission), immediately upon return to Earth (R+0) and 30 days following return (R+30). Plasma LL-37, HNP 1-3 and lysozyme concentrations were determined by ELISA. Saliva Epstein-Barr virus (EBV), varicella zoster virus (VZV) and urine cytomegalovirus (CMV) DNA levels were quantified by Real-Time PCR. Maximum likelihood linear mixed models (LMM) were used to determine main effects of time (pre-flight, in-flight, R+0 and R+30), and EBV, VZV and CMV viral shedding status (shedding or non-shedding) on the concentration of each AMPs. Results: Lower plasma levels of LL-37 were found at R+0, compared to pre-flight, in-flight and R+30 (-80.6%, -80.2% and -73.49% respectively; p \u3c 0.01). Plasma HNP 1-3 levels were elevated above pre-flight level during flight, at R+0 and R+30 (+24%, +40% and +17% respectively; p \u3c 0.01). Only those crewmembers found to shed CMV had a significant reduction in plasma LL-37 at R+0 (p \u3c 0.05). Similarly, crewmembers found to shed VZV at R+0 had lower HNP 1-3 concentrations than crewmembers who did not shed VZV (-68.9%; p \u3c 0.01). Finally, only those crewmembers who shed EBV had increased plasma levels of HNP 1-3 at R+0 (p \u3c 0.01). Plasma lysozyme levels were unaffected by spaceflight or latent viral shedding. Conclusion: Long-duration spaceflight alters plasma LL-37 and HNP 1-3 levels and are linked to the reactivation of latent herpesviruses. The in-flight changes observed for HNP 1-3 indicate that certain immune perturbations may be independent of launch/landing stress. Future studies are required to determine if spaceflight induced immune dysregulation increases the risk of an adverse health event before exploration-class planetary missions (i.e. to Mars) can be considered

Negative phase time for Scattering at Quantum Wells: A Microwave Analogy Experiment

If a quantum mechanical particle is scattered by a potential well, the wave function of the particle can propagate with negative phase time. Due to the analogy of the Schr\"odinger and the Helmholtz equation this phenomenon is expected to be observable for electromagnetic wave propagation. Experimental data of electromagnetic wells realized by wave guides filled with different dielectrics confirm this conjecture now.Comment: 10 pages, 6 figure

Quantum Noise and Superluminal Propagation

Causal "superluminal" effects have recently been observed and discussed in various contexts. The question arises whether such effects could be observed with extremely weak pulses, and what would prevent the observation of an "optical tachyon." Aharonov, Reznik, and Stern (ARS) [Phys. Rev. Lett., vol. 81, 2190 (1998)] have argued that quantum noise will preclude the observation of a superluminal group velocity when the pulse consists of one or a few photons. In this paper we reconsider this question both in a general framework and in the specific example, suggested by Chiao, Kozhekin, and Kurizki [Phys. Rev. Lett., vol. 77, 1254 (1996)], of off-resonant, short-pulse propagation in an optical amplifier. We derive in the case of the amplifier a signal-to-noise ratio that is consistent with the general ARS conclusions when we impose their criteria for distinguishing between superluminal propagation and propagation at the speed c. However, results consistent with the semiclassical arguments of CKK are obtained if weaker criteria are imposed, in which case the signal can exceed the noise without being "exponentially large." We show that the quantum fluctuations of the field considered by ARS are closely related to superfluorescence noise. More generally we consider the implications of unitarity for superluminal propagation and quantum noise and study, in addition to the complete and truncated wavepackets considered by ARS, the residual wavepacket formed by their difference. This leads to the conclusion that the noise is mostly luminal and delayed with respect to the superluminal signal. In the limit of a very weak incident signal pulse, the superluminal signal will be dominated by the noise part, and the signal-to-noise ratio will therefore be very small.Comment: 30 pages, 1 figure, eps

13th Meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): alternative testing methodologies for organ toxicity.

In the past decade in vitro tests have been developed that represent a range of anatomic structure from perfused whole organs to subcellular fractions. To assess the use of in vitro tests for toxicity testing, we describe and evaluate the current status of organotypic cultures for the major target organs of toxic agents. This includes liver, kidney, neural tissue, the hematopoietic system, the immune system, reproductive organs, and the endocrine system. The second part of this report reviews the application of in vitro culture systems to organ specific toxicity and evaluates the application of these systems both in industry for safety assessment and in government for regulatory purposes. Members of the working group (WG) felt that access to high-quality human material is essential for better use of in vitro organ and tissue cultures in the risk assessment process. Therefore, research should focus on improving culture techniques that will allow better preservation of human material. The WG felt that it is also important to develop and make available relevant reference compounds for toxicity assessment in each organ system, to organize and make available via the Internet complete in vivo toxicity data, including human data, containing dose, end points, and toxicokinetics. The WG also recommended that research should be supported to identify and to validate biological end points for target organ toxicity to be used in alternative toxicity testing strategies