Face identification proficiency test designed using item response theory.

Measures of face-identification proficiency are essential to ensure accurate and consistent performance by professional forensic face examiners and others who perform face-identification tasks in applied scenarios. Current proficiency tests rely on static sets of stimulus items and so cannot be administered validly to the same individual multiple times. To create a proficiency test, a large number of items of "known" difficulty must be assembled. Multiple tests of equal difficulty can be constructed then using subsets of items. We introduce the Triad Identity Matching (TIM) test and evaluate it using item response theory (IRT). Participants view face-image "triads" (N = 225) (two images of one identity, one image of a different identity) and select the different identity. In Experiment 3, university students (N = 197) showed wide-ranging accuracy on the TIM test, and IRT modeling demonstrated that the TIM items span various difficulty levels. In Experiment 3, we used IRT-based item metrics to partition the test into subsets of specific difficulties. Simulations showed that subsets of the TIM items yielded reliable estimates of subject ability. In Experiments 3a and b, we found that the student-derived IRT model reliably evaluated the ability of non-student participants and that ability generalized across different test sessions. In Experiment 3c, we show that TIM test performance correlates with other common face-recognition tests. In summary, the TIM test provides a starting point for developing a framework that is flexible and calibrated to measure proficiency across various ability levels (e.g., professionals or populations with face-processing deficits).

Standards for clinical trials for treating TB.

BACKGROUND: The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.METHODS: A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.RESULTS: Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.CONCLUSION: These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.

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.

A realist approach to understanding alliancing within Local Government public health and social care service provision.

BACKGROUND: Within the current context of continued austerity and post-pandemic recovery, it remains important that Local Government services address the increasing needs of residents as cost-effectively as possible. Alliancing, whereby services work collaboratively focusing on the 'whole-system', has gained popularity as a tool with the potential to support collaborative whole systems approaches. This synthesis aims to identify how alliancing can be successfully operationalised in the commissioning of public health, wider National Health Service (NHS) and social care-related services. METHODS: A realist literature synthesis was undertaken in order to identify underlying generative mechanisms associated with alliancing, the contextual conditions surrounding the implementation and operationalisation of the alliancing approach mechanisms, and the outcomes produced as a result. An iterative approach was taken, using a recent systematic review of the effectiveness of Alliancing, online database searches, and grey literature searches. RESULTS: Three mechanistic components were identified within the data as being core to the successful implementation of alliances in public health and social care-related services within Local Government: (i) Achieving a system-level approach; (ii) placing local populations at the heart of the system; and (iii) creating a cultural shift. Programme theories were postulated within these components. CONCLUSIONS: The alliancing approach offers an opportunity to achieve system-level change with the potential to benefit local populations. The realist synthesis approach taken within this study has provided insights into the necessary contextual and mechanistic factors of the Alliancing approach, above and beyond effectiveness outcomes typically collected through more conventional evaluation methodologies.

Kappa Opioid Receptors in Mesolimbic Terminals Mediate Escalation of Cocaine Consumption.

Increases in drug consumption over time, also known as escalation, is a key behavioral component of substance use disorder (SUD) that is related to potential harm to users, such as overdose. Studying escalation also allows researchers to investigate the transition from casual drug use to more SUD-like drug use. Understanding the neurobiological systems that drive this transition will inform therapeutic treatments in the aim to prevent increases in drug use and the development of SUD. The kappa opioid receptor (KOR) system is typically known for its role in negative affect, which is commonly found in SUD as well. Furthermore, the KOR system has also been implicated in drug use and importantly, modulating the negative effects of drug use. However, the specific neuronal subpopulation expressing KOR involved has not been identified. Here, we first demonstrated that pharmacologically inhibiting KOR in the nucleus accumbens core (NAcC), as a whole, blocks cocaine escalation under long-access self-administration conditions. We then demonstrated that KOR expressed on ventral tegmental area (VTA) neurons but not NAcC neurons is sufficient for blocking cocaine escalation by utilizing a novel virally-mediated CRISPR-SaCas9 knock-out of the oprk1 gene. Together, this suggests that activation of KOR on VTA terminals in the NAcC drives the transition to the SUD-like phenotype of escalation of cocaine consumption.

A comparison of clinical development pathways to advance tuberculosis regimen development.

BACKGROUND: Current tuberculosis (TB) regimen development pathways are slow and in urgent need of innovation. We investigated novel phase IIc and seamless phase II/III trials utilizing multi-arm multi-stage and Bayesian response adaptive randomization trial designs to select promising combination regimens in a platform adaptive trial. METHODS: Clinical trial simulation tools were built using predictive and validated parametric survival models of time to culture conversion (intermediate endpoint) and time to TB-related unfavorable outcome (final endpoint). This integrative clinical trial simulation tool was used to explore and optimize design parameters for aforementioned trial designs. RESULTS: Both multi-arm multi-stage and Bayesian response adaptive randomization designs were able to reliably graduate desirable regimens in ≥ 95% of trial simulations and reliably stop suboptimal regimens in ≥ 90% of trial simulations. Overall, adaptive phase IIc designs reduced patient enrollment by 17% and 25% with multi-arm multi-stage and Bayesian response adaptive randomization designs respectively compared to the conventional sequential approach, while seamless designs reduced study duration by 2.6 and 3.5 years respectively (typically ≥ 8.5 years for standard sequential approach). CONCLUSIONS: In this study, we demonstrate that adaptive trial designs are suitable for TB regimen development, and we provide plausible design parameters for a platform adaptive trial. Ultimately trial design and specification of design parameters will depend on clinical trial objectives. To support decision-making for clinical trial designs in contemporary TB regimen development, we provide a flexible clinical trial simulation tool that can be used to explore and optimize design features and parameters.

Factors associated with screening failure and study withdrawal in multidrug-resistant TB.

SETTING: Multidrug-resistant TB (MDR-TB) clinical trial in Lima, Peru and Cape Town, South Africa.OBJECTIVE: To identify baseline factors associated with screening failure and study withdrawal in an MDR-TB clinical trial.DESIGN: We screened patients for a randomized, blinded, Phase II trial which assessed culture conversion over the first 6 months of treatment with varying doses of levofloxacin plus an optimized background regimen (ClinicalTrials.gov: NCT01918397). We identified factors for screening failure and study withdrawal using Poisson regression to calculate prevalence ratios and Cox proportional hazard regression to calculate hazard ratios. We adjusted for factors with P < 0.2.RESULTS: Of the 255 patients screened, 144 (56.5%) failed screening. The most common reason for screening failure was an unsuitable resistance profile on sputum-based molecular susceptibility testing (n = 105, 72.9%). No significant baseline predictors of screening failure were identified in the multivariable model. Of the 111 who were enrolled, 33 (30%) failed to complete treatment, mostly for non-adherence and consent withdrawal. No baseline factors predicted study withdrawal in the multivariable model.CONCLUSION: No baseline factors were independently associated with either screening failure or study withdrawal in this secondary analysis of a MDR-TB clinical trial.

Aerosol delivery of star polymer-siRNA nanoparticles as a therapeutic strategy to inhibit lung tumor growth.

Lung cancer is a major contributor to cancer-related death worldwide. siRNA nanomedicines are powerful tools for cancer therapeutics. However, there are challenges to overcome to increase siRNA delivery to solid tumors, including penetration of nanoparticles into a complex microenvironment following systemic delivery while avoiding rapid clearance by the reticuloendothelial system, and limited siRNA release from endosomes once inside the cell. Here we characterized cell uptake, intracellular trafficking, and gene silencing activity of miktoarm star polymer (PDMAEMA-POEGMA) nanoparticles (star nanoparticles) complexed to siRNA in lung cancer cells. We investigated the potential of nebulized star-siRNA nanoparticles to accumulate into orthotopic mouse lung tumors to inhibit expression of two genes [ßIII-tubulin, Polo-Like Kinase 1 (PLK1)] which: 1) are upregulated in lung cancer cells; 2) promote tumor growth; and 3) are difficult to inhibit using chemical drugs. Star-siRNA nanoparticles internalized into lung cancer cells and escaped the endo-lysosomal pathway to inhibit target gene expression in lung cancer cells in vitro. Nebulized star-siRNA nanoparticles accumulated into lungs and silenced the expression of ßIII-tubulin and PLK1 in mouse lung tumors, delaying aggressive tumor growth. These results demonstrate a proof-of-concept for aerosol delivery of star-siRNA nanoparticles as a novel therapeutic strategy to inhibit lung tumor growth.

An assessment of introducers used for airway management.

Different introducers are available to assist with tracheal intubation. Subtle differences in the design of introducers can have a marked effect on safety and performance. The Difficult Airway Society's Airway Device Evaluation Project Team proposal states that devices should only be purchased for which there is at least a case-control study on patients assessing airway devices. However, resources are not currently available to carry out a case-control study on all introducers available on the market. This study comprised a laboratory and manikin-based investigation to identify introducers that could be suitable for clinical investigation. We included six different introducers in laboratory-based assessments (design characteristics) and manikin-based assessments involving the participation of 30 anaesthetists. Each anaesthetist attempted placement in the manikin's trachea with each of the six introducers in a random order. Outcomes included first-time insertion success rate; insertion success rate; number of attempts; time to placement; and distance placed. Each anaesthetist also completed a questionnaire. First-time insertion success rate depended significantly on the introducer used (p = 0.0016) and varied from 47% (Armstrong and P3) to 77% (Intersurgical and Frova). Median time to placement (including oesophageal placement) varied from 10 s (Eschmann and Frova) to 20 s (P3) (p = 0.0025). Median time to successful placement in the trachea varied from 9 s (Frova) to 22 s (Armstrong) (p = 0.037). We found that the Armstrong and P3 devices were not as acceptable as other introducers and, without significant improvements to their design and characteristics, the use of these devices in studies on patients is questionable. The study protocol is suitable for differentiating between different introducers and could be used as a basis for assessing other types of devices.

Forensic facial examiners versus super-recognizers: Evaluating behavior beyond accuracy.

We evaluated the detailed, behavioral properties of face matching performance in two specialist groups: forensic facial examiners and super-recognizers. Both groups compare faces to determine identity with high accuracy and outperform the general population. Typically, facial examiners are highly trained; super-recognizers rely on natural ability. We found distinct behaviors between these two groups. Examiners used the full 7-point identity judgment scale (-3: "different"; +3: "same"). Super-recognizers' judgments clustered toward highly confident decisions. Examiners' judgments for same- and different-identities were symmetric across the scale midpoint (0); super-recognizers' judgments were not. Examiners showed higher identity judgment agreement than super-recognizers. Despite these qualitative differences, both groups showed insight into their own accuracy: more confident people and those who rated the task to be easier tended to be more accurate. Altogether, we show to better understand and interpret judgments according to the nature of someone's facial expertise, evaluations should assess more than accuracy.

Evaluating newly approved drugs for multidrug-resistant tuberculosis (endTB): study protocol for an adaptive, multi-country randomized controlled trial.

BACKGROUND: Treatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB. Its use is only conditionally recommended because of very low-quality evidence underpinning the recommendation. Novel combinations of newer and repurposed drugs bring hope in the fight against MDR/RR-TB, but their use has not been optimized in all-oral, shorter regimens. This has greatly limited their impact on the burden of disease. There is, therefore, dire need for high-quality evidence on the performance of new, shortened, injectable-sparing regimens for MDR-TB which can be adapted to individual patients and different settings. METHODS: endTB is a phase III, pragmatic, multi-country, adaptive, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of shorter treatment regimens containing new drugs for patients with fluoroquinolone-susceptible, rifampin-resistant tuberculosis. Study participants are randomized to either the control arm, based on the current standard of care for MDR/RR-TB, or to one of five 39-week multi-drug regimens containing newly approved and repurposed drugs. Study participation in all arms lasts at least 73 and up to 104 weeks post-randomization. Randomization is response-adapted using interim Bayesian analysis of efficacy endpoints. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 750 patients across 6 arms affords at least 80% power to detect the non-inferiority of at least 1 (and up to 3) experimental regimens, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per protocol populations. DISCUSSION: The lack of a safe and effective regimen that can be used in all patients is a major obstacle to delivering appropriate treatment to all patients with active MDR/RR-TB. Identifying multiple shorter, safe, and effective regimens has the potential to greatly reduce the burden of this deadly disease worldwide. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02754765. Registered on 28 April 2016; the record was last updated for study protocol version 3.3, on 27 August 2019.

A systematic review of endpoint definitions in late phase pulmonary tuberculosis therapeutic trials.

BACKGROUND: Safe, more efficacious treatments are needed to address the considerable morbidity and mortality associated with pulmonary tuberculosis (TB). However, the current practice in TB therapeutics trials is to use composite binary outcomes, which in the absence of standardization may inflate false positive and negative errors in evaluating regimens. The lack of standardization of outcomes is a barrier to the identification of highly efficacious regimens and the introduction of innovative methodologies METHODS: We conducted a systematic review of trials designed to advance new pulmonary TB drugs or regimens for regulatory approval and inform practice guidelines. Trials were primarily identified from the WHO International Clinical Trial Registry Platform (ICTRP). Only trials that collected post-treatment follow-up data and enrolled at least 100 patients were included. Protocols and Statistical Analysis Plans (SAP) for eligible trials from 1995 to the present were obtained from trial investigators. Details of outcome data, both explicit and implied, were abstracted and organized into three broad categories: favorable, unfavorable, and not assessable. Within these categories, individual trial definitions were recorded and collated, and areas of broad consensus and disagreement were identified and described. RESULTS: From 2205 trials in any way related to TB, 51 were selected for protocol and SAP review, from which 31 were both eligible and had accessible documentation. Within the three designated categories, we found broad consensus in the definitions of favorable and unfavorable outcomes, although specific details were not always provided, and when explicitly addressed, were heterogeneous. Favorable outcomes were handled the most consistently but were widely variable with respect to specification. In some cases, the same events were defined differently by different protocols, particularly in distinguishing unfavorable from not assessable events. Death was often interpreted as conditional on cause. Patients who did not complete the study because of withdrawal or loss to follow-up presented a particular challenge to consistent interpretation and analytic treatment of outcomes. CONCLUSIONS: In a review of 31 clinical trials, we found that outcome definitions were heterogeneous, highlighting the need to establish clearer specification and a move towards universal standardization of outcomes across pulmonary TB trials. The ICH E9 (R1) addendum provides guidelines for undertaking and achieving this goal. PROSPERO REGISTRATION: PROSPERO CRD42020197993 . Registration 11 August 2020.

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.

Accuracy comparison across face recognition algorithms: Where are we on measuring race bias?

Previous generations of face recognition algorithms differ in accuracy for images of different races (race bias). Here, we present the possible underlying factors (data-driven and scenario modeling) and methodological considerations for assessing race bias in algorithms. We discuss data-driven factors (e.g., image quality, image population statistics, and algorithm architecture), and scenario modeling factors that consider the role of the "user" of the algorithm (e.g., threshold decisions and demographic constraints). To illustrate how these issues apply, we present data from four face recognition algorithms (a previous-generation algorithm and three deep convolutional neural networks, DCNNs) for East Asian and Caucasian faces. First, dataset difficulty affected both overall recognition accuracy and race bias, such that race bias increased with item difficulty. Second, for all four algorithms, the degree of bias varied depending on the identification decision threshold. To achieve equal false accept rates (FARs), East Asian faces required higher identification thresholds than Caucasian faces, for all algorithms. Third, demographic constraints on the formulation of the distributions used in the test, impacted estimates of algorithm accuracy. We conclude that race bias needs to be measured for individual applications and we provide a checklist for measuring this bias in face recognition algorithms.

Investigation of the efficacy of the short regimen for rifampicin-resistant TB from the STREAM trial.

BACKGROUND: The STREAM trial demonstrated that a 9-11-month "short" regimen had non-inferior efficacy and comparable safety to a 20+ month "long" regimen for the treatment of rifampicin-resistant tuberculosis. Imbalance in the components of the composite primary outcome merited further investigation. METHODS: Firstly, the STREAM primary outcomes were mapped to alternatives in current use, including WHO programmatic outcome definitions and other recently proposed modifications for programmatic or research purposes. Secondly, the outcomes were re-classified according to the likelihood that it was a Failure or Relapse (FoR) event on a 5-point Likert scale: Definite, Probable, Possible, Unlikely, and Highly Unlikely. Sensitivity analyses were employed to explore the impact of informative censoring. The protocol-defined modified intention-to-treat (MITT) analysis population was used for all analyses. RESULTS: Cure on the short regimen ranged from 75.1 to 84.2% across five alternative outcomes. However, between-regimens results did not exceed 1.3% in favor of the long regimen (95% CI upper bound 10.1%), similar to the primary efficacy results from the trial. Considering only Definite or Probable FoR events, there was weak evidence of a higher risk of FoR in the short regimen, HR 2.19 (95%CI 0.90, 5.35), p = 0.076; considering only Definite FoR events, the evidence was stronger, HR 3.53 (95%CI 1.05, 11.87), p = 0.030. Cumulative number of grade 3-4 AEs was the strongest predictor of censoring. Considering a larger effect of informative censoring attenuated treatment differences, although 95% CI were very wide. CONCLUSION: Five alternative outcome definitions gave similar overall results. The risk of failure or relapse (FoR) may be higher in the short regimen than in the long regimen, highlighting the importance of how loss to follow-up and other censoring is accounted for in analyses. The outcome of time to FoR should be considered as a primary outcome for future drug-sensitive and drug-resistant TB treatment trials, provided sensitivity analyses exploring the impact of departures from independent censoring are also included.

Electronic personal assessment questionnaire for vascular conditions (ePAQ-VAS): development and validity.

BACKGROUND: This paper describes the development and validation of an electronic personal assessment questionnaire for vascular conditions (ePAQ-VAS) that captures the symptomatology, quality of life and clinically relevant data of patients presenting to vascular services. METHODS: A two-stage survey was conducted in patients attending a tertiary vascular department. Patients completed the ePAQ-VAS remotely online, or on site using an electronic tablet. In the first stage of the survey, the responses were used to perform confirmatory factor analysis to assess the construct validity and remove redundant items. The internal reliability of disease-specific scales was investigated. In the second stage of the survey, the acceptability, known-group validity, test-retest reliability, and responsiveness of ePAQ-VAS was assessed. RESULTS: In total, 721 patients completed ePAQ-VAS. Their mean(s.d.) age was 63·5(15·7) years and 468 (64·9 per cent) were men. Some 553 patients (76·7 per cent) completed the questionnaire in clinic and the remainder completed the questionnaire online. The results of the confirmatory factor analysis confirmed the conceptual model for ePAQ-VAS structure and eliminated six items. Internal reliability was acceptable for all the scales (Cronbach's α greater than 0·7). The test-retest reliability measured by the intraclass correlation coefficient ranged from 0·65 to 0·99. The results showed that the instrument was responsive over time with the standardized response mean ranging from 0·69 to 1·60. CONCLUSION: ePAQ-VAS is a holistic data-collection process that is relevant to vascular service users and has potential to contribute to patient-focused care and the collection of aggregate data for service evaluation. A demonstration version of the final version of ePAQ can be viewed at http://demo-questionnaire.epaq.co.uk/home/project?id=VASC_1.7&page=1.

ANTECEDENTES: Este artículo describe el desarrollo y la validación de un cuestionario electrónico de evaluación personal para enfermedades vasculares (ePAQ-VAS) que incluye la sintomatología, la calidad de vida y los datos clínicamente relevantes para los pacientes que son atendidos en los servicios de patología vascular. MÉTODOS: Se llevó a cabo una encuesta en dos fases entre los pacientes atendidos en un servicio de patología vascular de tercer nivel. Los pacientes completaron el cuestionario ePAQ-VAS a distancia en línea o bien en el centro hospitalario mediante una tableta electrónica. En la primera fase de la encuesta, las respuestas se utilizaron para realizar un análisis factorial de confirmación para evaluar la validez del diseño y eliminar los elementos redundantes. Se investigó la fiabilidad interna de las escalas específicas de la enfermedad. En la segunda fase de la encuesta, se evaluó la aceptabilidad, la validez de grupo conocida, la fiabilidad test-retest y la capacidad de respuesta del ePAQ-VAS. RESULTADOS: En total, 721 pacientes completaron el ePAQ-VAS, la edad media fue de 63,5 años (DE 15,7); el 64,9% eran varones (468); el 76% de los pacientes (553) completaron el cuestionario en la clínica y los pacientes restantes lo hicieron electrónicamente a distancia. Los resultados del análisis factorial de confirmación confirmaron el modelo conceptual para la estructura ePAQ-VAS y eliminaron seis ítems. La fiabilidad interna fue aceptable para todas las escalas (alfa de Cronbach > 0,7). La fiabilidad test-retest medida por el coeficiente de correlación intraclase osciló entre 0,65-0,99. Los resultados mostraron que el instrumento responde con el tiempo con una media de respuesta estandarizada que varía de 0,69 a 1,60. CONCLUSIÓN: El ePAQ-VAS es un proceso holístico de recopilación de datos que es relevante para los usuarios de servicios de patología vascular y tiene el potencial de contribuir a la atención centrada en el paciente y a la recopilación de datos agregados para la evaluación del servicio.

Performance comparison of Yb:YAG ceramics and crystal gain material in a large-area, high-energy, high average-power diode-pumped laser.

We compare for the first time the influence of different Yb:YAG gain media on the performance of a large-area, high average-power laser system with an output energy of up to 6 J. Monocrystalline slabs grown by a new technique without central growth defect are compared with ceramics. Small signal gain, maximum output energy and thermal lensing are compared for ceramic slabs with co-sintered amplified spontaneous emission (ASE) absorber cladding, monocrystalline slab with and without optically bonded ASE absorber cladding, and surface structured monocrystalline slabs. We show that these large monocrystals with optically bonded absorber cladding have similar performance to cladded ceramics, so far the only material for high-energy Yb:YAG lasers.

Rapid bactericidal effect of cinnamon bark essential oil against Pseudomonas aeruginosa.

AIMS: This study aimed to identify the most effective antimicrobial agent from a selection of essential oils (EO) and investigate its bactericidal properties against Pseudomonas aeruginosa. METHODS AND RESULTS: The disc diffusion assay and minimal inhibitory/bactericidal concentration tests were used to identify antimicrobial potential. Several oils exhibited antimicrobial effects at concentrations as low as 0·03% (v/v). Significantly, cinnamon (Cinnamomum zeylanicum) bark EO exhibited a broad-spectrum activity against Gram-negative and Gram-positive bacteria and showed bacteriostatic and bactericidal effects against P. aeruginosa PAO1 at 0·125% (v/v) and all other tested organisms, including known multidrug resistant species. Time-kill assays and metabolic activity tests showed cinnamon oil to exhibit rapid killing, with bactericidal activity observed in ≤6 min at ≥0·5% (v/v). Furthermore, scanning electron microscopy and a membrane permeability assay indicated damage to membrane integrity, loss of turgor and cell collapse. CONCLUSION: Cinnamon bark EO is a broad-spectrum antimicrobial agent capable of rapid killing at low concentrations. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides a sound basis for further investigation of the potential of cinnamon bark EO as an alternative to conventional antimicrobial products due to its fast-acting bactericidal properties at low concentrations.

Risk of brainstem necrosis in pediatric patients with central nervous system malignancies after pencil beam scanning proton therapy.

Background: Radiation therapy (RT) plays an important role in management of pediatric central nervous system (CNS) malignancies. Centers are increasingly utilizing pencil beam scanning proton therapy (PBS-PT). However, the risk of brainstem necrosis has not yet been reported. In this study, we evaluate the rate of brainstem necrosis in pediatric patients with CNS malignancies treated with PBS-PT.Material and methods: Pediatric patients with non-hematologic CNS malignancies treated with PBS-PT who received dose to the brainstem were included. All procedures were approved by the institutional review board. Brainstem necrosis was defined as symptomatic toxicity. The actuarial rate was analyzed by the Kaplan Meier method.Results: One hundred and sixty-six consecutive patients were reviewed. Median age was 10 years (range 0.5-21 years). Four patients (2.4%) had prior radiation. Median maximum brainstem dose in the treated course was 55.4 Gy[RBE] (range 0.15-61.4 Gy[RBE]). In patients with prior RT, cumulative median maximum brainstem dose was 98.0 Gy [RBE] (range 17.0-111.0 Gy [RBE]). Median follow up was 19.6 months (range, 2.0-63.0). One patient who had previously been treated with twice-daily radiation therapy and intrathecal (IT) methotrexate experienced brainstem necrosis. The actuarial incidence of brainstem necrosis was 0.7% at 24 months (95% CI 0.1-5.1%).Conclusion: The rate of symptomatic brainstem necrosis was extremely low after treatment with PBS-PT in this study. Further work to clarify clinical and dosimetric parameters associated with risk of brainstem necrosis after PBS-PT is needed.