Demonstration of stable, long-term operation of a nanosecond pulsed DPSSL at 10 J, 100 Hz.

We report on stable, long-term operation of a diode-pumped solid-state laser (DPSSL) amplifying 15 ns pulses at 1029.5 nm wavelength to 10 J energy at 100 Hz pulse rate, corresponding to 1 kW average power, with 25.4% optical-to-optical efficiency. The laser was operated at this level for over 45 minutes (∼3 · 105 shots) in two separate runs with a rms energy stability of 1%. The laser was also operated at 7 J, 100 Hz for 4 hours (1.44 · 106 shots) with a rms long-term energy stability of 1% and no need for user intervention. To the best of our knowledge, this is the first time that long-term reliable amplification of a kW-class high energy nanosecond pulsed DPSSL at 100 Hz has been demonstrated.

Evaluation of a novel ELISA test using synthetic mycolic acid antigens for serodiagnosis of non-tuberculous mycobacterial (NTM) infections.

The diagnosis of non-tuberculous mycobacteria (NTM) is a particular challenge in people with cystic fibrosis. Current standard diagnostic approaches rely on serial sputum culture, which is resource demanding, dependent on patient expectoration and may be compromised by excessive decontamination, conventional bacterial overgrowth and masking by concomitant oral and nebulised antibiotics. An alternative rapid, reliable and inexpensive diagnostic method is therefore urgently needed. Serum of patients with Mycobacterium abscessus infection and chronic suppurative lung disease without NTM infection was tested against an array of novel synthetic mycolic acids, identical or similar to natural components of mycobacterial cell walls, and glycopeptidolipid (GPL)-core antigen, which has previously been investigated in Mycobacterium avium pulmonary infection. Diagnostic accuracy of individual antigens and combination of various antigens were calculated. An ELISA using individual trehalose dimycolates and GPL-core antigen was able to effectively distinguish serum from infected and non-infected individuals with a specificity of 88% and a sensitivity of up to 88%, which increased to 88% sensitivity and 93% specificity by combining several antigens in the test. These results suggest synthetic mycolic acid antigens, used individually or in combination with GPL-core antigen could be successfully used to distinguish patients with M. abscessus infection from disease controls.

Generation of Joule-level green bursts of nanosecond pulses from a DPSSL amplifier.

A new approach to generation of a burst of high-energy green pulses by placing a high-energy multi-slab Yb:YAG DPSSL amplifier and SHG crystal inside a regenerative cavity is presented. In a proof-of-concept test, stable generation of a burst of six green (515 nm) pulses, each 10 ns in duration and separated by 29.4 ns (34 MHz), with 2.0 J total energy has been demonstrated at 1 Hz from a non-optimized ring cavity design. A maximum individual green pulse energy of 580 mJ was produced from a 1.78 J circulating infrared (1030 nm) pulse (average fluence 0.9 J/cm2), corresponding to a SHG conversion efficiency of 32%. Experimental results have been compared with predicted performance from a simple model. Efficient generation of a burst of high energy green pulses offers an attractive pump source for Ti:Sa amplifiers, providing the potential to reduce the impact of amplified stimulated emission by reducing instantaneous transverse gain.

High energy, high pulse rate laser operation using crystalline adhesive-free bonded Yb:YAG slabs.

We report on the successful amplification of 10 ns pulses to 10 J energy at 10 Hz in a DiPOLE laser amplifier using crystalline Yb:YAG/Cr:YAG composite slabs manufactured using adhesive-free bonding (AFB) technology. We demonstrate that bonded slabs are suitable for operation in high energy cryogenic laser amplifiers. We also report on frequency doubling of the beam amplified in the bonded slabs. When the pulse energy of the output infrared beam is set to 5 J, a pulse energy of 3.9 J is achieved in the green (corresponding to 78% conversion efficiency). Results demonstrate that AFB technology is suitable for producing large-sized gain material slabs and can overcome current limitations in the manufacture of large-aperture gain material pieces. We believe this work will facilitate energy scaling of high energy lasers where aperture scaling of optical elements is not achievable via conventional manufacturing techniques.

Improved stability second harmonic conversion of a diode-pumped Yb:YAG laser at the 0.5 kW level.

We report on efficient and stable, type-I phase-matched second harmonic conversion of a nanosecond high-energy, diode-pumped, Yb:YAG laser. With a frequency-doubling crystal in an enclosed, temperature controller with optical windows, 0.5% energy stability was achieved for approximately half an hour. This resulted in 48.9 J pulses at 10 Hz (489 W) and a conversion efficiency of 73.8%. These results are particularly important for stable and reliable operation of high-energy, frequency-doubled lasers.

Community-wide Screening for Tuberculosis in a High-Prevalence Setting.

BACKGROUND: The World Health Organization has set ambitious targets for the global elimination of tuberculosis. However, these targets will not be achieved at the current rate of progress. METHODS: We performed a cluster-randomized, controlled trial in Ca Mau Province, Vietnam, to evaluate the effectiveness of active community-wide screening, as compared with standard passive case detection alone, for reducing the prevalence of tuberculosis. Persons 15 years of age or older who resided in 60 intervention clusters (subcommunes) were screened for pulmonary tuberculosis, regardless of symptoms, annually for 3 years, beginning in 2014, by means of rapid nucleic acid amplification testing of spontaneously expectorated sputum samples. Active screening was not performed in the 60 control clusters in the first 3 years. The primary outcome, measured in the fourth year, was the prevalence of microbiologically confirmed pulmonary tuberculosis among persons 15 years of age or older. The secondary outcome was the prevalence of tuberculosis infection, as assessed by an interferon gamma release assay in the fourth year, among children born in 2012. RESULTS: In the fourth-year prevalence survey, we tested 42,150 participants in the intervention group and 41,680 participants in the control group. A total of 53 participants in the intervention group (126 per 100,000 population) and 94 participants in the control group (226 per 100,000) had pulmonary tuberculosis, as confirmed by a positive nucleic acid amplification test for Mycobacterium tuberculosis (prevalence ratio, 0.56; 95% confidence interval [CI], 0.40 to 0.78; P<0.001). The prevalence of tuberculosis infection in children born in 2012 was 3.3% in the intervention group and 2.6% in the control group (prevalence ratio, 1.29; 95% CI, 0.70 to 2.36; P = 0.42). CONCLUSIONS: Three years of community-wide screening in persons 15 years of age or older who resided in Ca Mau Province, Vietnam, resulted in a lower prevalence of pulmonary tuberculosis in the fourth year than standard passive case detection alone. (Funded by the Australian National Health and Medical Research Council; ACT3 Australian New Zealand Clinical Trials Registry number, ACTRN12614000372684.).

Modelling and measurement of thermal stress-induced depolarisation in high energy, high repetition rate diode-pumped Yb:YAG lasers.

In this paper, we present a model to predict thermal stress-induced birefringence in high energy, high repetition rate diode-pumped Yb:YAG lasers. The model calculates thermal depolarisation as a function of gain medium geometry, pump power, cooling parameters, and input polarisation state. We show that model predictions are in good agreement with experimental observations carried out on a DiPOLE 100 J, 10 Hz laser amplifier. We show that single-pass depolarisation strongly depends on input polarisation state and pumping parameters. In the absence of any depolarisation compensation scheme, depolarisation varies over a range between 5% and 40%. The strong dependence of thermal stress-induced depolarisation on input polarisation indicates that, in the case of multipass amplifiers, the use of waveplates after every pass can reduce depolarisation losses significantly. We expect that this study will assist in the design and optimisation of Yb:YAG lasers.

Second and third harmonic conversion of a kilowatt average power, 100-J-level diode pumped Yb:YAG laser in large aperture LBO.

We report on the successful demonstration of second and third harmonic conversion of a high pulse energy, high average power 1030 nm diode pumped Yb-doped yttrium aluminum garnet (Yb:YAG) nanosecond pulsed laser in a large aperture lithium triborate (LBO) crystal. We demonstrated generation of 59.7 J at 10 Hz (597 W) at 515 nm (second harmonic) and of 65.0 J at 1 Hz (65 W) at 343 nm (third harmonic), with efficiencies of 66% and 68%, respectively. These results, to the best of our knowledge, represent the highest energy and power reported for frequency conversion to green and UV-A wavelengths.

150 J DPSSL operating at 1.5 kW level.

We report on obtaining output energy of 146 J in 10 ns long pulses at 10 Hz repetition rate from Bivoj, a multi-Joule multi-slab cryogenic gas-cooled diode pumped solid state laser, by overcoming its damage threshold bottleneck. This is a 40% energy and power increase of the laser system in comparison to our previous publication and to the most powerful multi-Joule high power laser system.

Stable high-energy, high-repetition-rate, frequency doubling in a large aperture temperature-controlled LBO at 515 nm.

We report on frequency doubling of high-energy, high-repetition-rate ns pulses from a cryogenically gas cooled, multi-slab Yb:YAG laser system, using a type-I phase-matched lithium triborate (LBO) crystal. Pulse energy of 4.3 J was extracted at 515 nm for a fundamental input of 5.4 J at 10 Hz (54 W), corresponding to a conversion efficiency of 77%. However, during long-term operation, a significant reduction of efficiency (more than 25%) was observed owing to the phase mismatch arising due to the temperature-dependent refractive index change in the crystal. This forced frequent angle tuning of the crystal to recover the second-harmonic generation (SHG) energy. More than a five-fold improvement in energy stability of SHG was observed when the LBO crystal was mounted in an oven, and its temperature was controlled at 27°C. Stable frequency doubling with 0.8% rms energy variation was achieved at a higher input power of 74 W when the LBO temperature was controlled at 50°C.

Using hospital auxiliary worker and 24-h TB services as potential tools to overcome in-hospital TB delays: a quasi-experimental study.

BACKGROUND: In-hospital logistic management barriers (LMB) are considered to be important risk factors for delays in TB diagnosis and treatment initiation (TB-dt), which perpetuates TB transmission and the development of TB morbidity and mortality. We assessed the contribution of hospital auxiliary workers (HAWs) and 24-h TB laboratory services using Xpert (24h-Xpert) on the delays in TB-dt and TB mortality at Beira Central Hospital, Mozambique. METHODS: A quasi-experimental design was used. Implementation strategy-HAWs and laboratory technicians were selected and trained, accordingly. Interventions-having trained HAW and TB laboratory technicians as expediters of TB LMB issues and assurer of 24h-Xpert, respectively. Implementation outcomes-time from hospital admission to sputum examination results, time from hospital admission to treatment initiation, proportion of same-day TB cases diagnosed, initiated TB treatment, and TB patient with unfavorable outcome after hospitalization (hospital TB mortality). A nonparametric test was used to test the differences between groups and adjusted OR (95% CI) were computed using multivariate logistic regression. RESULTS: We recruited 522 TB patients. Median (IQR) age was 34 (16) years, and 52% were from intervention site, 58% males, 60% new case of TB, 12% MDR-TB, 72% TB/HIV co-infected, and 43% on HIV treatment at admission. In the intervention hospital, 93% of patients had same-day TB-dt in comparison with a median (IQR) time of 15 (2) days in the control hospital. TB mortality in the intervention hospital was lower than that in the control hospital (13% vs 49%). TB patients admitted to the intervention hospital were nine times more likely to obtain an early laboratory diagnosis of TB, six times more likely to reduce delays in TB treatment initiation, and eight times less likely to die, when compared to those who were admitted to the control hospital, adjusting for other factors. CONCLUSION: In-hospital delays in TB-dt and high TB mortality in Mozambique are common and probably due, in part, to LMB amenable to poor-quality TB care. Task shifting of TB logistic management services to HAWs and lower laboratory technicians, to ensure 24h-Xpert through "on-the-spot strategy," may contribute to timely TB detection, proper treatment, and reduction of TB mortality.

Public trust and global biobank networks.

BACKGROUND: Biobanks provide an important foundation for genomic and personalised medicine. In order to enhance their scientific power and scope, they are increasingly becoming part of national or international networks. Public trust is essential in fostering public engagement, encouraging donation to, and facilitating public funding for biobanks. Globalisation and networking of biobanking may challenge this trust. METHODS: We report the results of an Australian study examining public attitudes to the networking and globalisation of biobanks. The study used quantitative and qualitative methods in conjunction with bioethical analysis in order to determine factors that may contribute to, and threaten, trust. RESULTS: Our results indicate a generally high level of trust in biobanks and in medical research more broadly. Key factors that can reduce perceived trustworthiness of biobanks are commercialisation and involvement in global networking. CONCLUSIONS: We conclude that robust ethical oversight and governance standards can both promote trust in global biobanking and ensure that this trust is warranted.

Eliminating latent tuberculosis in low-burden settings: are the principal beneficiaries to be disadvantaged groups or the broader population?

Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide, and the burdens of this disease continue to track prior disadvantage. In order to galvanise a coordinated global response, WHO has recently launched the End TB Campaign that aims to eliminate TB by 2050. Key to this is the introduction of population screening programmes in low-burden settings to identify and treat people who have latent TB infection (LTBI). The defining features of LTBI are: that it is not an active disease but confers an increased risk of disease; the socially disadvantaged are those most in danger and uncertainty persists as to who will be harmed or benefitted from screening-led prophylactic interventions. Systematic screening programmes that include surveillance, case-finding and treatment of asymptomatic individuals inevitably redistribute the risk of harms and the potential for benefits within a population. The extent to which those targeted within such programmes should be exposed to higher levels of risk in the pursuit of individual or community benefits requires careful consideration prior to implementation. As currently construed, it remains unclear who stands to benefit most from how LTBI screening in high-income countries is being organised, and whose health is being prioritised: members of disadvantaged groups or the broader community. Unless the aims of LTBI screening programmes in these settings are made transparent and their prioritisation ethically justified, there is a significant danger that such a targeted intervention will further disadvantage those who have the least capacity to bear the burdens of TB elimination.

Mapping the illness trajectories of insomnia: a biographical disruption?

The insomnia illness experience can be conceptualised as a form of biographical disruption. Using a critical interpretive phenomenological lens 51 in-depth semi-structured interviews were conducted with patients from specialist sleep and psychology clinics (n = 22) and the general community (n = 29). Patients' narratives revealed key phases of their illness trajectories as they recognise, rethink and respond to insomnia. Their biographical events served as reference points for both patient groups to make sense of their illness experiences as they transitioned from a perceived state of sleeplessness to clinical insomnia. The innate biological process of sleep at night and the sleep-dependent daytime psychosocial function exerted a negative bi-directional effect, creating a continuous circuit of disruption. Coping mechanisms were inspired by the participants' immediate social environment and centred on sociocultural motifs of relaxation and alertness to break the 'circuit'. Access to specialist clinic services appeared to be contingent on the richness of resources in one's social network and surrounding environment rather than the clinical severity of the disease alone. Treatment that can simultaneously target the night time and daytime consequences of insomnia resonates closely with participants' depiction of insomnia as both a physiological and a psychosocial phenomenon.

A systems approach to animal communication.

Why animal communication displays are so complex and how they have evolved are active foci of research with a long and rich history. Progress towards an evolutionary analysis of signal complexity, however, has been constrained by a lack of hypotheses to explain similarities and/or differences in signalling systems across taxa. To address this, we advocate incorporating a systems approach into studies of animal communication--an approach that includes comprehensive experimental designs and data collection in combination with the implementation of systems concepts and tools. A systems approach evaluates overall display architecture, including how components interact to alter function, and how function varies in different states of the system. We provide a brief overview of the current state of the field, including a focus on select studies that highlight the dynamic nature of animal signalling. We then introduce core concepts from systems biology (redundancy, degeneracy, pluripotentiality, and modularity) and discuss their relationships with system properties (e.g. robustness, flexibility, evolvability). We translate systems concepts into an animal communication framework and accentuate their utility through a case study. Finally, we demonstrate how consideration of the system-level organization of animal communication poses new practical research questions that will aid our understanding of how and why animal displays are so complex.

High energy, high repetition rate, second harmonic generation in large aperture DKDP, YCOB, and LBO crystals.

We report on type-I phase-matched second harmonic generation (SHG) in three nonlinear crystals: DKDP (98% deuteration), YCOB (XZ plane), and LBO (XY plane), of 8 J, 10 Hz cryogenic gas cooled Yb:YAG laser operating at 1029.5 nm. DKDP exhibited an efficiency of 45% at a peak fundamental intensity of 0.24 GW/cm2 for 10 Hz operation at 10 ns. At the same intensity and repetition rate, YCOB and LBO showed 50% and 65% conversion efficiencies, respectively. Significant improvement in conversion efficiency, to a maximum of 82%, was demonstrated in LBO at 0.7 GW/cm2 and 10 Hz, generating output energy of 5.6 J at 514.75 nm, without damage or degradation. However, no improvement in conversion efficiency was recorded for YCOB at this increased intensity. Additionally, we present theoretically calculated temperature maps for both 10 J and 100 J operation at 10 Hz, and discuss the suitability of these three crystals for frequency conversion of a 100 J, 10 Hz diode pumped solid state laser (DPSSL).

100 J-level nanosecond pulsed diode pumped solid state laser.

We report on the successful demonstration of a 100 J-level, diode pumped solid state laser based on cryogenic gas cooled, multi-slab ceramic Yb:YAG amplifier technology. When operated at 175 K, the system delivered a pulse energy of 107 J at a 1 Hz repetition rate and 10 ns pulse duration, pumped by 506 J of diode energy at 940 nm, corresponding to an optical-to-optical efficiency of 21%. To the best of our knowledge, this represents the highest energy obtained from a nanosecond pulsed diode pumped solid state laser. This demonstration confirms the energy scalability of the diode pumped optical laser for experiments laser architecture.

SOCIAL, HISTORICAL AND CULTURAL DIMENSIONS OF TUBERCULOSIS.

Tuberculosis (TB) researchers and clinicians, by virtue of the social disease they study, are drawn into an engagement with ways of understanding illness that extend beyond the strictly biomedical model. Primers on social science concepts directly relevant to TB, however, are lacking. The particularities of TB disease mean that certain social science concepts are more relevant than others. Concepts such as structural violence can seem complicated and off-putting. Other concepts, such as gender, can seem so familiar that they are left relatively unexplored. An intimate familiarity with the social dimensions of disease is valuable, particularly for infectious diseases, because the social model is an important complement to the biomedical model. This review article offers an important introduction to a selection of concepts directly relevant to TB from health sociology, medical anthropology and social cognitive theory. The article has pedagogical utility and also serves as a useful refresher for those researchers already engaged in this genre of work. The conceptual tools of health sociology, medical anthropology and social cognitive theory offer insightful ways to examine the social, historical and cultural dimensions of public health. By recognizing cultural experience as a central force shaping human interactions with the world, TB researchers and clinicians develop a more nuanced consideration of how health, illness and medical treatment are understood, interpreted and confronted.

Tuberculosis and mental health in the Asia-Pacific.

OBJECTIVE: This opinion piece encourages mental health researchers and clinicians to engage with mental health issues among tuberculosis patients in the Asia-Pacific region in a culturally appropriate and ethical manner. The diversity of cultural contexts and the high burden of tuberculosis throughout the Asia-Pacific presents significant challenges. Research into tuberculosis and mental illness in this region is an opportunity to develop more nuanced models of mental illness and treatment, while simultaneously contributing meaningfully to regional tuberculosis care and prevention. CONCLUSIONS: We overview key issues in tuberculosis and mental illness co-morbidity, highlight ethical concerns and advocate for a regional approach to tuberculosis and mental health that is consistent with the transnational challenges presented by this airborne infectious disease. Integrating tuberculosis and mental health services will go a long way to addressing the needs of vulnerable populations and stopping the transmission of one of the world's biggest infectious killers.

DiPOLE: a 10 J, 10 Hz cryogenic gas cooled multi-slab nanosecond Yb:YAG laser.

The Diode Pumped Optical Laser for Experiments (DiPOLE) project at the Central Laser Facility aims to develop a scalable, efficient high pulse energy diode pumped laser amplifier system based on cryogenic gas cooled, multi-slab ceramic Yb:YAG technology. We present recent results obtained from a scaled down prototype laser system designed for operation at 10 Hz pulse repetition rate. At 140 K, the system generated 10.8 J of energy in a 10 ns pulse at 1029.5 nm when pumped by 48 J of diode energy at 940 nm, corresponding to an optical to optical conversion efficiency of 22.5%. To our knowledge, this represents the highest pulse energy obtained from a cryo cooled Yb laser to date and the highest efficiency achieved by a multi-Joule diode pumped solid state laser system. Additionally, we demonstrated shot-to-shot energy stability of 0.85% rms for the system operated at 7 J, 10 Hz during several runs lasting up to 6 hours, with more than 50 hours in total. We also demonstrated pulse shaping capability and report on beam, wavefront and focal spot quality.