Low-light-level nonlinear optics with slow light

Electromagnetically induced transparency in an optically thick, cold medium creates a unique system where pulse-propagation velocities may be orders of magnitude less than $c$ and optical nonlinearities become exceedingly large. As a result, nonlinear processes may be efficient at low-light levels. Using an atomic system with three, independent channels, we demonstrate a quantum interference switch where a laser pulse with an energy density of $\sim23$ photons per $\lambda^2/(2\pi)$ causes a 1/e absorption of a second pulse.Comment: to be published in PR

Accommodating false positives within acoustic spatial capture–recapture, with variable source levels, noisy bearings and an inhomogeneous spatial density

Funding: Tiago Marques was partly supported by CEAUL (funded by FCT - Fundação para a Ciência e a Tecnologia, Portugal, through the project UIDB/00006/2020).Passive acoustic monitoring is a promising method for surveying wildlife populations that are easier to detect acoustically than visually. When animal vocalisations can be uniquely identified on an array of sensors, the potential exists to estimate population density through acoustic spatial capture–recapture (ASCR). However, sound classification is imperfect, and in some situations, a high proportion of sounds detected on just a single sensor (‘singletons’) are not from the target species. We present a case study of bowhead whale calls (Baleana mysticetus) collected in the Beaufort Sea in 2010 containing such false positives. We propose a novel extension of ASCR that is robust to false positives by truncating singletons and conditioning on calls being detected by at least two sensors. We allow for individual-level detection heterogeneity through modelling a variable sound source level, model inhomogeneous call spatial density, and include bearings with varying measurement error. We show via simulation that the method produces near-unbiased estimates when correctly specified. Ignoring source-level variation resulted in a strong negative bias, while ignoring inhomogeneous density resulted in severe positive bias. The case study analysis indicated a band of higher call density approximately 30 km from shore; 59.8% of singletons were estimated to have been false positives.Publisher PDFPeer reviewe

What constitutes brilliant aged care? : a qualitative study of practices that exceed expectation

Aim: This study aimed to explore what constitutes brilliant aged care. Background: Although many aged care services do not offer the care that older people and carers need and want, some perform better. Rather than focus on problems with aged care, this study examined brilliant aged care—practices that exceeded expectation. Design: The methodology for this study was informed by grounded theory, under-pinned by constructionism to socially construct meaning. Methods: This study invited nominations for a Brilliant Award via a survey, and inter-views with the nominees via web conference. After receiving survey responses from 10 nominators, interviews were conducted with 12 nominees. Data were analysed using reflexive thematic analysis and documented according to COREQ guidelines to optimise rigour and transparency. Results: According to participants, brilliant aged care involved being relationally at-tuned to older people, a deep understanding of the older person, recognition of aged care as more than a job, innovative practices and permission to reprioritise. Conclusions: This study suggests that, in aged care, brilliance happens. It emphasises the importance of meaningful connections and relationships in aged care, where thoughtful acts acknowledge an older person's value and humanity as well as creativity and innovation. Relevance to Clinical Practice: For those who manage and deliver aged care, the findings suggest that small practice changes can make a positive difference to older people. Brilliant aged care can involve acts of empathy; enthusiasm for aged care; innovative practices, even those that are small scale; and reprioritising workplace tasks to spend time with older people. For policymakers, this study highlights the need to recognise and raise the profile of the pockets of brilliance within the aged care sector. This might be achieved via awards and other initiatives that serve to celebrate and learn from brilliance in its myriad forms. Patient or Public Contribution: The nominees, who included carers, were invited to participate in workshops with other carers and older people to co-design a model of brilliant aged care, during which workshop participants discussed and critiqued the findings constructed from the data

A comparison of three methods for estimating call densities of migrating bowhead whales using passive acoustic monitoring

TAM thanks partial support by Centro de Estatistica e Aplicações, Universidade de Lisboa (funded by FCT—Fundação para a Ciência e a Tecnologia, Portugal, through the project UID/MAT/00006/2013).Various methods for estimating animal density from visual data, including distance sampling (DS) and spatially explicit capture-recapture (SECR), have recently been adapted for estimating call density using passive acoustic monitoring (PAM) data, e.g., recordings of animal calls. Here we summarize three methods available for passive acoustic density estimation: plot sampling, DS, and SECR. The first two require distances from the sensors to calling animals (which are obtained by triangulating calls matched among sensors), but SECR only requires matching (not localizing) calls among sensors. We compare via simulation what biases can arise when assumptions underlying these methods are violated. We use insights gleaned from the simulation to compare the performance of the methods when applied to a case study: bowhead whale call data collected from arrays of directional acoustic sensors at five sites in the Beaufort Sea during the fall migration 2007–2014. Call detections were manually extracted from the recordings by human observers simultaneously scanning spectrograms of recordings from a given site. The large discrepancies between estimates derived using SECR and the other two methods were likely caused primarily by the manual detection procedure leading to non-independent detections among sensors, while errors in estimated distances between detected calls and sensors also contributed to the observed patterns. Our study is among the first to provide a direct comparison of the three methods applied to PAM data and highlights the importance that all assumptions of an analysis method need to be met for correct inference.Publisher PDFPeer reviewe

Mouse genome-wide association studies and systems genetics uncover the genetic architecture associated with hepatic pharmacokinetic and pharmacodynamic properties of a constrained ethyl antisense oligonucleotide targeting Malat1

Antisense oligonucleotides (ASOs) have demonstrated variation of efficacy in patient populations. This has prompted our investigation into the contribution of genetic architecture to ASO pharmacokinetics (PK) and pharmacodynamics (PD). Genome wide association (GWA) and transcriptomic analysis in a hybrid mouse diversity panel (HMDP) were used to identify and validate novel genes involved in the uptake and efficacy of a single dose of a Malat1 constrained ethyl (cEt) modified ASO. The GWA of the HMDP identified two significant associations on chromosomes 4 and 10 with hepatic Malat1 ASO concentrations. Stabilin 2 (Stab2) and vesicle associated membrane protein 3 (Vamp3) were identified by ciseQTL analysis. HMDP strains with lower Stab2 expression and Stab2 KO mice displayed significantly lower PK than strains with higher Stab2 expression and the wild type (WT) animals respectively, confirming the role of Stab2 in regulating hepatic Malat1 ASO uptake. GWA examining ASO efficacy uncovered three loci associated with Malat1 potency: Small Subunit Processome Component (Utp11l) on chromosome 4, Rho associated coiled-coil containing protein kinase 2 (Rock2) and Aci-reductone dioxygenase (Adi1) on chromosome 12. Our results demonstrate the utility of mouse GWAS using the HMDP in detecting genes capable of impacting the uptake of ASOs, and identifies genes critical for the activity of ASOs in vivo

Conceptualising hepatitis C stigma: A thematic synthesis of qualitative research.

BACKGROUND: Stigma is an important element in the experience of living with chronic viral hepatitis B (HBV) and C (HCV), impacting healthcare access and uptake as well as health outcomes. Conceptualisations of stigma in research are, however, often assumed and implicit. This study aimed to synthesise and critically engage with the qualitative literature to provide an overarching conceptualisation of stigma as it pertains to viral hepatitis. METHODS: We critically reviewed qualitative literature that mobilised concepts or theories of stigma in relation to viral hepatitis. We searched seven electronic databases for peer-reviewed literature from 2000 to 2019. Given a dearth of conceptual literature on HBV stigma, we conducted a thematic analysis of concepts deployed to theorise stigma in relation to HCV. RESULTS: We found 13 studies that conceptualised stigma in relation to HCV, yet none for HBV. We synthesise the analytical findings of these studies and explore how HCV is theorised in relation to four themes: 'identity', 'embodiment', 'institutionalisation', and 'structuration'. Taken together, these themes illustrate the way in which HCV stigma manifests as the confluence of normative assumptions of socially unacceptable practices relating to HCV, such as injecting drug use and sexual behaviours; attitudes towards socially excluded populations; and fears of contracting a contagious and chronic illness. As such, operating within political, social, and economic systems, HCV stigma can act to silence the needs of those with HCV through misrecognising the multifaceted identities of individuals with HCV and structural determinants of health. Stigma, which is built and perpetuated by institutional arrangements, as well as in social processes and policies, shapes deservedness to, as well as engagements with, health and social care. CONCLUSION: While commonly employed as a framing concept, much research lacks explicit theoretical or critical engagement on how stigma is conceptualised. There is a tendency for qualitative, empirical research to focus on risk factors shaping individual behaviour change, rather than on risk contexts and socio-structural change. Approaches to address stigma in relation to HCV must consider how stigma operates throughout social processes and is embedded in systems of power and normalised in institutional operating systems

Advancing Our Functional Understanding of Host–Microbiota Interactions: A Need for New Types of Studies

Multicellular life evolved in the presence of microorganisms and formed complex associations with their microbiota, the sum of all associated archaea, bacteria, fungi, and viruses. These associations greatly affect the health and life history of the host, which led to a new understanding of “self” and establishment of the “metaorganism” concept.1 The Collaborative Research Centre (CRC) 1182 aims at elucidating the evolution and function of metaorganisms. Its annual conference, the Young Investigator Research Day (YIRD), serves as a platform for scientists of various disciplines to share novel findings on host–microbiota interactions, thereby providing a comprehensive overview of recent developments and new directions in metaorganism research. Even though we have gained tremendous insights into the composition and dynamics of host‐associated microbial communities and their correlations with host health and disease, it also became evident that moving from correlative toward functional studies is needed to examine the underlying mechanisms of interactions within the metaorganism. Non‐classical model organisms in particular possess significant potential to functionally address many open questions in metaorganism research. Here, we suggest and introduce a roadmap moving from correlation toward a functional understanding of host–microbiota interactions and highlight its potential in emerging ecological, agricultural, and translational medical applications

An Australian general practice based strategy to improve chronic disease prevention, and its impact on patient reported outcomes: Evaluation of the preventive evidence into practice cluster randomised controlled trial

© 2017 The Author(s). Background: Implementing evidence-based chronic disease prevention with a practice-wide population is challenging in primary care. Methods: PEP Intervention practices received education, clinical audit and feedback and practice facilitation. Patients (40 69 years) without chronic disease from trial and control practices were invited to participate in baseline and 12 month follow up questionnaires. Patient-recalled receipt of GP services and referral, and the proportion of patients at risk were compared over time and between intervention and control groups. Mean difference in BMI, diet and physical activity between baseline and follow up were calculated and compared using a paired t-test. Change in the proportion of patients meeting the definition for physical activity diet and weight risk was calculated using McNemar's test and multilevel analysis was used to determine the effect of the intervention on follow-up scores. Results: Five hundred eighty nine patients completed both questionnaires. No significant changes were found in the proportion of patients reporting a BP, cholesterol, glucose or weight check in either group. Less than one in six at-risk patients reported receiving lifestyle advice or referral at baseline with little change at follow up. More intervention patients reported attempts to improve their diet and reduce weight. Mean score improved for diet in the intervention group (p = 0.04) but self-reported BMI and PA risk did not significantly change in either group. There was no significant change in the proportion of patients who reported being at-risk for diet, PA or weight, and no changes in PA, diet and BMI in multilevel linear regression adjusted for patient age, sex, practice size and state. There was good fidelity to the intervention but practices varied in their capacity to address changes. Conclusions: The lack of measurable effect within this trial may be attributable to the complexities around behaviour change and/or system change. This trial highlights some of the challenges in providing suitable chronic disease preventive interventions which are both scalable to whole practice populations and meet the needs of diverse practice structures. Trial registration: Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12612000578808 (29/5/2012). This trial registration is retrospective as our first patient returned their consent on the 21/5/2012. Patient recruitment was ongoing until 31/10/2012

Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology

Equipping providers to offer novel MPTs: Developing counseling messages for the Dual Prevention Pill in clinical studies and beyond

IntroductionThe pipeline for multi-purpose prevention technologies includes products that simultaneously prevent HIV, pregnancy and/or other sexually transmitted infections. Among these, the Dual Prevention Pill (DPP) is a daily pill co-formulating oral pre-exposure prophylaxis (PrEP), and combined oral contraception (COC). Clinical cross-over acceptability studies for the DPP require training providers to counsel on a combined product. From February 2021–April 2022, a working group of eight HIV and FP experts with clinical and implementation expertise developed counseling recommendations for the DPP based on existing PrEP/COC guidance.Assessment of policy/guidelines options and implicationsThe working group conducted a mapping of counseling messages from COC and oral PrEP guidance and provider training materials. Six topics were prioritized: uptake, missed pills, side effects, discontinuation and switching, drug interactions and monitoring. Additional evidence and experts were consulted to answer outstanding questions and counseling recommendations for the DPP were developed. Missed pills was the topic with the most complexity, raising questions about whether women could “double up” on missed pills or skip the last week of the pack to recover protection faster. Uptake required aligning the time to reach protective levels for both DPP components and explaining the need to take DPP pills during week 4 of the pack. The potential intensity of DPP side effects, given the combination of oral PrEP with COC, was an important consideration. Discontinuation and switching looked at managing risk of HIV and unintended pregnancy when stopping or switching from the DPP. Guidance on drug interactions contended with differing contraindications for COC and PrEP. Monitoring required balancing clinical requirements with potential user burden.Actionable recommendationsThe working group developed counseling recommendations for the DPP to be tested in clinical acceptability studies. Uptake: Take one pill every day for the DPP until the pack is empty. Days 1–21 contain COC and oral PrEP. Days 22–28 do not contain COC to allow for monthly bleeding, but do contain oral PrEP and pills should be taken to maintain HIV protection. Take the DPP for 7 consecutive days to reach protective levels against pregnancy and HIV. Missed pills: If you miss 1 pill multiple times in a month or 2+ consecutive pills, take the DPP as soon as you remember. Do not take more than 2 pills in a day. If 2+ consecutive pills are missed, only take the last missed pill and discard the other missed pills. Side effects: You may experience side effects when you start using the DPP, including changes to monthly bleeding. Side effects are typically mild and go away without treatment. Discontinuation/switching: If you decide to discontinue use of the DPP, but want to be protected from HIV and/or unintended pregnancy, in most cases, you can begin using PrEP or another contraceptive method right away. Drug interactions: There are no drug-drug interactions from combining oral PrEP and COC in the DPP. Certain medications are not recommended due to their contraindication with oral PrEP or COC. Monitoring: You will need to get an HIV test prior to initiating or restarting the DPP, and every 3 months during DPP use. Your provider may recommend other screening or testing.DiscussionDeveloping recommendations for the DPP as a novel MPT posed unique challenges, with implications for efficacy, cost, and user and provider comprehension and burden. Incorporating counseling recommendations into clinical cross-over acceptability studies allows for real-time feedback from providers and users. Supporting women with information to use the DPP correctly and confidently is critically important for eventual scale and commercialization