Search

Introduction: Synthetic DNA technology is rapidly emerging as a key driver of innovation in the fields of medicine, biotechnology, and more. But it also poses significant risk, particularly in lowering barriers to the production of dangerous pathogens and toxins. At present, oversight of this technology is voluntarily coordinated among synthetic DNA providers and stakeholders, and detailed understanding of security processes, infrastructures, and insights from these providers is imperative to understand how to best mitigate the inherent risks of this technology. Objectives: In this study, we aimed to determine the trends, outliers, strengths, and gaps in current DNA provider security practices through a broad survey of the gene synthesis field. Methods: We interviewed synthetic DNA providers and stakeholders about their customer and sequence screening procedures. Respondents were divided into groups based on membership in the International Gene Synthesis Consortium, nationality, whether they were a new or established company, and whether they synthesize de novo DNA or not. We then performed meta-analysis and intergroup analysis to elucidate larger trends and points of variance. Results: In total, we interviewed 18 companies. We found that synthetic DNA providers and stakeholders tend to operate under a "zero-trust model" for screenings and utilize common governmental and private resources to navigate international import/export policies. Major variabilities were identified in the sensitivity of screening, monitoring and evaluation practices, screening pipelines, and approaches to synthetic oligonucleotide screening. In addition, we identified a significant vulnerability of lacking awareness among providers of formal law enforcement reporting procedures. Conclusion: Collectively, we observed significant heterogeneity in security practice throughout the field, reflective of the current lack of codified oversight for DNA synthesis. The results presented in this study provide insight into the specifics, strengths, and shortcomings of current DNA provider security practices, and are important considerations for the biosecurity community in ongoing deliberations of if, when, and how to approach oversight of synthetic DNA technology. [ABSTRACT FROM AUTHOR]

This article is a review of the book "Projective identification: a contemporary introduction" by Waska R. The book aims to introduce the concept of projective identification in the contemporary Kleinian tradition. The author uses clinical examples and rhyming mnemonics to describe the therapist's approach to understanding and interpreting projective identification. The book emphasizes the normal use of projective identification as a form of communication, but also acknowledges its potential for destructiveness. It explores the therapist's role in containing and interpreting projective identification, as well as the challenges and benefits of working with this dynamic unconscious phantasy. [Extracted from the article]

This book review discusses "Forensic Group Psychotherapy: The Portman Clinic Approach" by J. Woods and A. William. The book focuses on offering outpatient group psychotherapy to violent and sexual offenders at the Portman Clinic in London. It explores the principles underlying forensic work and the challenges faced by therapists in working with this patient group. The review also highlights the implications of therapist gender and the transference scenarios that arise in therapy groups. Overall, the book provides valuable insights into forensic group psychotherapy and its unique approach to treating violent and sexual offenders. [Extracted from the article]

The Quantitative Randomized Response Technique (RRT) can be used by researchers to obtain honest answers to questions that, due to their sensitive (socially undesirable, dangerous, or even illegal) nature, might otherwise invoke partially or completely falsified responses. Over the years, Quantitative RRT models, sometimes called Scrambling models, have been developed to incorporate such advancements as mixture, optionality and enhanced trust, each of which has important benefits. However, no single model incorporates all of these features. In this study, we propose just such a unified model, which we call the Mixture Optional Enhanced Trust (MOET) model. After developing methodologies to assess MOET based on standard approaches and using them to explore the key characteristics of the new model, we show that MOET has superior efficiency compared to the Quantitative Optional Enhanced Trust (OET) model. We also show that use of the model's mixture capability allows practitioners to optimally balance the model's efficiency with its privacy, making the model adaptable to a wide variety of research scenarios. [ABSTRACT FROM AUTHOR]

Beta‐decay half‐lives for the free neutron, for 6He and 8He, and for 8Li are calculated ab initio from geometrical thermodynamics arguments, independently of any quantum mechanics. Half‐lives for the decay of 8Be to two alphas and for the disintegration of the tetraneutron are also calculated. The calculated values are close to those experimentally observed. [ABSTRACT FROM AUTHOR]

The Principle of Indifference ('PI': the simplest non-informative prior in Bayesian probability) has been shown to lead to paradoxes since Bertrand (1889). Von Mises (1928) introduced the 'Wine/Water Paradox' as a resonant example of a 'Bertrand paradox', which has been presented as demonstrating that the PI must be rejected. We now resolve these paradoxes using a Maximum Entropy (MaxEnt) treatment of the PI that also includes information provided by Benford's 'Law of Anomalous Numbers' (1938). We show that the PI should be understood to represent a family of informationally identical MaxEnt solutions, each solution being identified with its own explicitly justified boundary condition. In particular, our solution to the Wine/Water Paradox exploits Benford's Law to construct a non-uniform distribution representing the universal constraint of scale invariance, which is a physical consequence of the Second Law of Thermodynamics. [ABSTRACT FROM AUTHOR]

We exploit the properties of complex time to obtain an analytical relationship based on considerations of causality between the two Noether-conserved quantities of a system: its Hamiltonian and its entropy production. In natural units, when complexified, the one is simply the Wick-rotated complex conjugate of the other. A Hilbert transform relation is constructed in the formalism of quantitative geometrical thermodynamics, which enables system irreversibility to be handled analytically within a framework that unifies both the microscopic and macroscopic scales, and which also unifies the treatment of both reversibility and irreversibility as complementary parts of a single physical description. In particular, the thermodynamics of two unitary entities are considered: the alpha particle, which is absolutely stable (that is, trivially reversible with zero entropy production), and a black hole whose unconditional irreversibility is characterized by a non-zero entropy production, for which we show an alternate derivation, confirming our previous one. The thermodynamics of a canonical decaying harmonic oscillator are also considered. In this treatment, the complexification of time also enables a meaningful physical interpretation of both "imaginary time" and "imaginary energy". [ABSTRACT FROM AUTHOR]

Key content: Uterine artery embolisation can be used as a minimally invasive technique for the management of benign gynaecological conditions refractory to other medical treatments.The Royal College of Obstetricians and Gynaecologists (RCOG) and the Royal College of Radiologists (RCR) recommend the use of interventional radiology (IR) techniques for the prophylaxis and management of postpartum haemorrhage.Interventional radiologists can percutaneously drain post‐operative collections or tubo‐ovarian abscesses.Interventional radiology plays a role in the management of early pregnancy complications such as ectopic pregnancy and gestational trophoblastic disease.Interventional radiology can aid the care of patients with gynaecological malignancies. Learning objectives: To understand the various IR techniques applicable to obstetrics and gynaecologyTo understand the risk and benefit profiles of these techniquesTo understand when the techniques could be appropriate and how they compare to surgical alternatives Ethical issues: There are limited data regarding the use of some IR procedures owing to the ethical issues of using experimental techniques to treat pregnant women or women who wish to conceive.The availability of IR procedures is hospital specific so treatment is not available to all who may benefit. [ABSTRACT FROM AUTHOR]

Physics has been thought to truly represent reality since at least Galileo, and the foundations of physics are always established using philosophical ideas. In particular, the elegant naming of physical entities is usually very influential in the acceptance of physical theories. We here demonstrate (using current developments in thermodynamics as an example) that both the epistemology and the ontology of physics ultimately rest on poetic language. What we understand depends essentially on the language we use. We wish to establish our knowledge securely, but strictly speaking this is impossible using only analytic language. Knowledge of the meanings of things must use a natural language designed to express meaning, that is, poetic language. Although the world is really there, and although we can indeed know it truly, this knowledge is never either complete or certain but ultimately must rest on intuition. Reading a recently discovered artefact with a palaeo-Hebrew inscription as from the first century, we demonstrate from it that this ontological understanding long predates the Hellenic period. Poetic language is primary, both logically and temporally. [ABSTRACT FROM AUTHOR]

After having been observed regularly at Seal Cove, San Clemente Island, California, since 1994, the Guadalupe Murrelet (Synthliboramphus hypoleucus) was confirmed nesting successfully in an artificial nest on a rocky ledge above the cove in 2022. The incubating adults' identity and the two chicks' departure from the nest were confirmed by a trail camera. Another Guadalupe Murrelet nest at Santa Barbara Island in 2021 was only the second confirmed there. Though the populations of the Guadalupe Murrelet at San Clemente and Santa Barbara islands are apparently small, they are important in representing the only confirmed sites of the species' nesting away from Guadalupe and the San Benito islands. [ABSTRACT FROM AUTHOR]

Given the unprecedented scale of digital surveillance in the COVID-19 pandemic, designing and implementing digital technologies in ways that are equitable is critical now and in future epidemics and pandemics. Yet to date there has been very limited consideration about what is necessary to promote their equitable design and implementation. In this study, literature relating to the use of digital surveillance technologies during epidemics and pandemics was collected and thematically analyzed for ethical norms and concerns related to equity and social justice. Eleven norms are reported, including procedural fairness and inclusive approaches to design and implementation, designing to rectify or avoid exacerbating inequities, and fair access. Identified concerns relate to digital divides, stigma and discrimination, disparate risk of harm, and unfair design processes. We conclude by considering what dimensions of social justice the norms promote and whether identified concerns can be addressed by building the identified norms into technology design and implementation practice. [ABSTRACT FROM AUTHOR]

He concluded that Seth had a need to be seen for ' ... who I really am', a man with a more receptive, softer side, unlike and different from his own more aggressive father in real life (Diamond, [1], p. 22.). He argues that there is a male potential for penetrability and accessibility and that: ' ... there is a male interior space, an inner path to male receptivity ... ' (Diamond, [1], p. 19). Masculinity and its discontents: the male psyche and the inherent tensions of maturing manhood: Michael J. Diamond, New York, Routledge, 2021, 138 pp., £120. [Extracted from the article]

The nuclear matter and charge radii of the helium isotopes (A=4,6,8) are calculated by quantitative geometrical thermodynamics (QGT) taking as input the symmetry of the alpha‐particle, the very weak binding (and hence halo nature) of the heavier helium isotopes, and a characteristic length scale given by the proton size. The results follow by considering each isotope in its ground state, with QGT representing each system as a maximum entropy configuration that conforms to the Holographic Principle. This allows key geometric parameters to be determined from the number of degrees of freedom available. QGT treats 6He as a 4He core plus a concentric neutron shell comprising a holomorphic pair of neutrons, and the 8He neutron halo is treated as a holomorphic pair of holomorphic pairs. Considering that the information content of each system allows a correlation angle of 2π/3 between the holomorphic entities to be inferred, then the charge radii of the three isotopes can be calculated from the displacement of the 4He core from the center of mass. The calculations for the charge and matter radii of 4,6,8He agree closely with observed values. Similar QGT calculation of the sizes of the self‐conjugate A=4n nuclei {4He,8Be,12C,16O,20Ne,24Mg,28Si,32S,36Ar,40Ca} also agree well with experiment. [ABSTRACT FROM AUTHOR]

• Mobility codes do not accurately represent modern military mobility on organic soil. • Low ground pressure vehicles perform better on organic soil. • Organic soils have a wide variability of soil and vegetation conditions. Current political climates have generated a renewed interest in the northern regions of the world. These areas are known to have soft marshy peat, highly organic soils, and harsh winter climates. Current capabilities for vehicle mobility modeling on this terrain is limited and existing studies do not include contemporary military vehicles. This work presents mobility experiments of modern military vehicles at multiple field sites containing peat or highly organic soils that can be used to improve mobility modeling on these soils. Field experiments are being conducted during multiple seasons, including winter, spring, and summer. The vehicle traction, motion resistance, and hard surface rolling resistance of an instrumented High Mobility Multipurpose Wheeled Vehicle (HMMWV) and a Small Unit Support Vehicle (SUSV) were examined. The first is a common multi-purpose vehicle and the second is a vehicle designed to operate in these types of environments. This data set will provide the basis for model development and validation for vehicle mobility in highly organic soils. [ABSTRACT FROM AUTHOR]

• SVM's do a good job at classifying the difference between snow and pavement. • ROS and Pixhawk controllers together make a good inexpensive vehicle controller. • Artificial Intelligence algorithms can be trained from simple vehicle models. The US Army must update its vehicle fleet to be better equipped for potential future military conflicts in northern climates (US Army, 2017). This process involves considering manned, optionally manned, and unmanned vehicles as viable options in the future. Optionally manned and unmanned vehicles in the armed forces have substantial benefits because they can operate without direct driver input or are able to perform missions deemed too dangerous for troops. Optionally manned vehicles allow the driver to shift some, or all, focus away from the task of driving the vehicle. In some cases, these autonomous vehicles may perform better than a human driver by rapidly sensing and reacting to terrain changes. Onboard sensing and decision making are equally applicable to both fully autonomous and teleoperated vehicles. This work will focus on the terrain sensing, waypoint navigation, and teleoperation potential of an optionally manned or unmanned vehicle. Results from a vehicle demonstration on two different terrain conditions will provide the basis for additional terrain sensing and autonomous vehicle development work in the coming year. [ABSTRACT FROM AUTHOR]

Introduction: Thoracic Endovascular Aortic Repair (TEVAR) has become the procedure of choice for pathology involving the descending thoracic aorta since its approval by the FDA in 2005. Left subclavian artery (LSA) coverage is commonly required to facilitate an adequate proximal landing zone for the endograft. The traditional revascularization procedure of choice is carotid-subclavian bypass, however recent studies report complication rates as high as 29%—specifically phrenic nerve palsy in 25% of patients undergoing this procedure. Our aim is to present our experience using carotid-axillary bypass as a safe alternative to carotid-subclavian bypass. Methods: All patients undergoing carotid-axillary bypass for TEVAR with LSA coverage between June 2016 and September 2019 at a tertiary medical center were retrospectively identified. Short-term and long-term complications were identified and analyzed including: phrenic nerve, recurrent laryngeal nerve, and axillary nerve injuries, as well as local vascular complications requiring re-intervention. All perioperative chest radiographs were reviewed for new hemidiaphragm elevation to assess for phrenic nerve injuries. Results: 35 patients underwent carotid-axillary bypass in conjunction with TEVAR during this time period. The majority of bypasses were performed concurrently with TEVAR (80.0%, 28/35) utilizing GORE PROPATEN 8 mm externally supported vascular graft (91.4%, 32/35). The complication rate specific to carotid-axillary bypass was 14.3% (5/35). We observed a significantly lower (0%, 0/35, P < 0.01) rate of phrenic nerve palsy for carotid-axillary bypass compared to the previously reported 25% (27/107) for carotid-subclavian bypass. For patients with available follow-up imaging (85.7%, 30/35), there was a 100% patency rate at time intervals ranging from 0-1066 days (IQR = 3-37.8). Conclusion: Carotid-axillary bypass can be performed as a safe alternative to carotid-subclavian bypass for LSA coverage during TEVAR involving a more superficial anatomic course of dissection. Phrenic nerve palsy, a well-described complication of the traditional carotid-subclavian bypass, was not observed in this retrospective series. [ABSTRACT FROM AUTHOR]

The literature suggests that recent advances in research, such as genomic studies, may have further complicated consent processes due to the complex nature of these studies and unfamiliarity with the concepts and methodologies involved. Some empirical studies in Africa have reported that although there is general support for genomic studies, particularly on the reuse of samples, there are also concerns about how the interests of key stakeholders such as participants (i.e. sample donors) and the broader local communities from which samples are collected can and should be ascertained and protected. The focus of the paper by Mweemba et al. reports on the findings of a qualitative study with participants recruited for an H3Africa study on rheumatic heart disease in Zambia. The study suggests that conventional ethics standards and practices may not be sufficiently responsive to participant and community concerns and interests in addressing the ethical complexity of the ethical challenges in research. [Extracted from the article]

This work proves that stability of C60 is a geometrical property of the thermodynamics of the system: a significant methodological advance since a detailed treatment of the energetics may be avoidable. This approach may be fruitful, not only for fullerenes but also for general problems of molecular stability and in other applications of conformational chemistry. For the non‐chiral C60, C384, and the weakly‐chiral C28, C76 and C380 (of these, C380 and C384 are classed as "unspirallable"), Schlegel projections are used to show that these fullerenes can all be represented by pairs of spirals counter‐propagating in anti‐parallel (C2) symmetry. For C60, the high symmetry is used to construct an analytical approximation for the spherical double‐spirals, shown mathematically to be Maximum Entropy (MaxEnt) using the formalism of Quantitative Geometrical Thermodynamics (QGT). Therefore C60 is necessarily stable. This MaxEnt stability criterion is general, depending only on the geometry and not the kinematics of the system. The sense and degree of chirality for C76 and C380 is also quantified using a Shannon entropy‐based fragmentation metric. [ABSTRACT FROM AUTHOR]

Chest tube (CT) placement is among the most common procedures performed by trauma surgeons; evidence guiding CT management is limited and tends toward thoracic surgery patients. The study goal was to identify current CT management practices among trauma providers. We designed a Web-based multiple-choice survey to assess CT management practices of trauma providers who were active, senior, or provisional members (n = 1890) of the Eastern Association for the Surgery of Trauma and distributed via e-mail. Descriptive statistics were used. The response rate was 39% (n = 734). Ninety-one percent of respondents were attending surgeons, the remainder fellows or residents. Regarding experience, 36% of respondents had five or fewer years of practice, 54% 10 y or fewer, and 79% 20 y or fewer. Attendings were more likely than trainees to place pigtail catheters for stable patients with pneumothorax (PTX). Attendings with experience of <5 y were more likely to choose a pigtail than more experienced surgeons for elderly patients with PTX. Respondents preferred standard size CTs for hemothorax and unstable patients with PTX, and larger tubes for unstable patients with hemothorax. Most respondents (53%) perceived the quality of evidence for trauma CT management to be low and cited personal experience and training as the main factors driving their practice. Trauma CT management is variable and nonstandardized, depending mostly on clinician training and personal experience. Few surgeons identify their practice as evidence based. We offer compelling justification for the need for trauma CT management research to determine best practices. [ABSTRACT FROM AUTHOR]

The first protein structures revealed a complex web of weak interactions stabilising the three-dimensional shape of the molecule. Small molecule ligands were then found to exploit these same weak binding events to modulate protein function or act as substrates in enzymatic reactions. As the understanding of ligand-protein binding grew, it became possible to firstly predict how and where a particular small molecule might interact with a protein, and then to identify putative ligands for a specific protein site. Computer-aided drug discovery, based on the structure of target proteins, is now a well-established technique that has produced several marketed drugs. We present here an overview of the various methodologies being used for structure-based computer-aided drug discovery and comment on possible future developments in the field. [ABSTRACT FROM AUTHOR]

The Prenatal Assessment of Genome and Exomes (PAGE) project is a UK-wide study aiming to gain a better understanding of genetic variants causing developmental problems during pregnancy. A further aim of the study is to provide an evidence-base for the introduction of prenatal whole genome and exome sequencing (PWGES) into prenatal diagnostics provided by the NHS, which is expected in 2018. This paper presents the findings of a qualitative interview study undertaken with 20 health professionals and researchers involved in the PAGE project, and explores their implications for understandings of ‘good practice’ in the uses of prenatal genomics clinically. A number of critical issues are identified that will need to be addressed in the development of a model of good ethical practice for prenatal genomics: consent, management of expectations, return of results, and professional duties in the context of PWGES. The analysis presented identifies and illustrates a great deal of complexity and qualitative richness in these issues as they arise in the day-to-day work of genomics professionals. Inclusive, critical discussion of these findings, together with the findings from other empirical studies, normative analysis and scientific discoveries resulting from PAGE, will be required to inform the development of appropriate guidelines of good ethical practice that address the needs and concerns to be encountered in daily clinical practice. [ABSTRACT FROM AUTHOR]

Gain quenched lasers can satisfy the requirements for all-optical switches in communications and computing systems. Hitherto, these devices have lacked optical gain between the input beam and output beam, and have been limited to switching amplitude modulated optical signals. A simple model based on the laser rate equations demonstrates that quenched devices can convert wavelength modulated signals into amplitude modulated ones with programmable optical gain. The discussion includes the effect of carrier injection, laser construction, and type of heterostructure. [ABSTRACT FROM AUTHOR]

For Seamus Heaney translation was by no means peripheral to his literary project, but central to it, not least as a means of renewing his creative impetus and extending the reach of his work across multiple times and cultures. This essay examines the reasons behind Heaney's increasing immersion in Greek literature from the mid-1980s onwards. It examines how the political and ethical issues Sophocles addresses inPhiloctetesdrew him to the play, and identifies the contexts – international and local – which shapedThe Cure at Troy’s composition and reception. Unlike many previous discussions which dwell primarily on material Heaney added to the original, this essay offers a meticulous analysis of the entireCure. It evaluates the quality of its poetry and its relationship to Heaney's lyric work up to 1990 and after. A recurring focus of interest are those moments and extended passages where Heaney takes greatest pains to make the source text his own, to settle in and ‘colonize’ it. In demonstrating where, when and why divergences occur, his version is repeatedly compared and contrasted with those of four other eminent translators. What emerges from this is how fully he sought to re-imagine the characters and recast the Chorus, ensuring the audience's empathy for and engagement with these flawed specimens of humanity. [ABSTRACT FROM AUTHOR]

Purpose of the Study This qualitative study had three aims: (1) to interview a group of military nurses who had served in Afghanistan and Iraq, (2) to determine if the quantitative findings of the larger electronic survey resonated with veteran nurses, and (3) to identify other concerns and issues that were not addressed adequately in the survey. Description This was a focus group convened to review the results of survey research conducted by Stanton and colleagues in 2016. Based on informal feedback from survey respondents, the investigators decided that a follow-up qualitative study with veteran nurses in the focus group could review the data and analysis from this survey. The group met and reviewed the results and their conversations were recorded and analyzed. Methods A multistage focus group approach was used to convene three meetings of nurse veterans (N = 8) who had been deployed and had experienced the reintegration process. Results During all three interviews, participants reinforced many of the findings of the survey by Stanton and colleagues. A range of life course issues beyond the scope of the electronic survey was also identified by the focus group as problematic during deployment and as challenging during the reintegration process. Conclusions Military nurses and other medical caregiver groups might benefit from proactive planning and training that encourage/underscore the benefits of spirituality and mindfulness and other strategies that prepare and support them. Specific resources/toolkits that target common life course concerns have been initiated. [ABSTRACT FROM AUTHOR]

There has been a dramatic rise in the scale and scope of collaborative global health research. A number of structural and scientific factors explain this growth and there has been much discussion of these in the literature. Little, if any, attention has been paid, however, to the factors identified by scientists and other research actors as important to successful research collaboration. This is surprising given that their decisions are likely to play a key role in the sustainability and effectiveness of global health research initiatives. In this paper, we report on qualitative research with leading scientists involved in major international research collaborations about their views on good and bad collaborations and the factors that inform their decision-making about joining and participating actively in research networks. We identify and discuss eight factors that researchers see as essential in judging the merits of active participation in global health research collaborations: opportunities for active involvement in cutting-edge, interesting science; effective leadership; competence of potential partners in and commitment to good scientific practice; capacity building; respect for the needs, interests and agendas of partners; opportunities for discussion and disagreement; trust and confidence; and, justice and fairness in collaboration. Our findings suggest that the sustainability and effectiveness of global health research collaborations has an important ethical or moral dimension for the research actors involved. [ABSTRACT FROM AUTHOR]

Over 90% of deaths attributable to malaria are in African children under 5 years old. Yet, new treatments are often tested primarily in adult patients and extrapolations have proven to be sometimes invalid, especially in dosing regimens. For studies in severe malaria an additional complication is that the decline in severe malaria in adult patients precludes sufficiently powered trials in adults, before the intervention can be tested in the ultimate target group, paediatric severe malaria. In this paper we propose an alternative pathway to the development of drugs for use in paediatric severe malaria. We argue that following the classical phase I and II studies, small safety and efficacy studies using well-chosen surrogate endpoints in adult severe malaria be conducted, instead of larger mortality endpoint trials. If the drug appears safe and promising small pilot studies in paediatric severe malaria using the same endpoints can follow. Finally, with carefully observed safeguards in place to ensure high ethical standards, promising candidate interventions can be taken forward into mortality endpoint, well-powered, large paediatric studies in African children with severe malaria. Given the available research capacity, limited numbers of prudently selected interventions can be studied in phase III trials, and adaptive designs should be considered. [ABSTRACT FROM AUTHOR]

Objectives: In this paper we discuss the main ethical challenges related to the conduct of medicine quality surveys and make suggestions on how to address them.Method: Most evidence-based information regarding medicine quality derives from surveys. However, existing research ethical guidelines do not provide specific guidance for medicine quality surveys. Hence, those conducting surveys are often left wondering how to judge what counts as best practice. A list of the main ethical challenges in the design and conduct of surveys is presented.Results and Conclusions: It is vital that the design and conduct of medicine quality surveys uphold moral and ethical obligations and analyse the ethical implications and consequences of such work. These aspects include the impact on the local availability of and access to medicines; the confidentiality and privacy of the surveyors and the surveyed; questions as to whether outlet staff personnel should be told they are part of a survey; the need of ethical and regulatory approvals; and how the findings should be disseminated. Medicine quality surveys should ideally be conducted in partnership with the relevant national Medicine Regulatory Authorities. An international, but contextually sensitive, model of good ethical practice for such surveys is needed. [ABSTRACT FROM AUTHOR]

The fuelling of active galactic nuclei (AGN) - via material propagated through the galactic disc or via minor mergers - is expected to leave an imprint on the alignment of the sub-pc disc relative to the host galaxy's stellar disc. Determining the inclination of the inner disc usually relies on the launching angle of the jet; here instead we use the inclination derived from reflection fits to a sample of AGN. We determine the distorting effect of unmodelled Fe XXV/XXVI features and, via extensive simulations, determine the difference in disc inclination resulting from the use of RELXILL compared to REFLIONX. We compare inner disc inclinations to those for the host galaxy stellar disc derived from the Hubble formula and, via Monte Carlo simulations, find a strong lack of a correlation (at ≫5σ) implying either widespread feeding via mergers if we assume the sample to be homogeneous, or that radiative disc warps are distorting our view of the emission. However, we find that by removing a small (~1/5) subset of AGN, the remaining sample is consistent with random sampling of an underlying 1:1 correlation (at the 3σ level). A heterogenous sample would likely imply that our view is not dominated by radiative disc warps but instead by different feeding mechanisms with the majority consistent with coplanar accretion (although this may be the result of selection bias), whilst a smaller but not insignificant fraction may have been fuelled by minor mergers in the recent history of the host galaxy. [ABSTRACT FROM AUTHOR]

An enduring debate concerns how responsibility for patient safety should be distributed between organisational systems and individual professionals. Though rule-based, calculus-like approaches intended to support a 'just culture' have become popular, they perpetuate an asocial and atomised account. In this article, we use insights from practice theory - which sees organisational phenomena as accomplished in everyday actions, with individual agency and structural conditions as a mutually constitutive, dynamic duality - along with contributions from the political science and ethics literature as a starting point for analysis. Presenting ethnographic data from five hospitals, three in one high-income country and two in low-income countries, we offer an empirically informed, normative rethinking of the role of personal accountability, identifying the collective nature of the healthcare enterprise and the extent to which patient safety depends on contributions from many hands. We show that moral responsibility for actions and behaviours is an irreducible element of professional practice, but that individuals are not somehow 'outside' and separate from 'systems': they create, modify and are subject to the social forces that are an inescapable feature of any organisational system; each element acts on the other. Our work illustrates starkly the structuring effects of the broader institutional and socioeconomic context on opportunities to 'be good'. These findings imply that one of the key responsibilities of organisations and wider institutions in relation to patient safety is the fostering of the conditions of moral community. [ABSTRACT FROM AUTHOR]

Axion-like particles (ALPs) are well-motivated extensions of the Standard Model of Particle Physics and a generic prediction of some string theories. X-ray observations of bright active galactic nuclei (AGNs) hosted by rich clusters of galaxies are excellent probes of very-light ALPs, with masses log (m a / eV) < − 12.0. We evaluate the potential of future X-ray observatories, particularly Athena and the proposed AXIS, to constrain ALPs via observations of cluster-hosted AGNs, taking NGC 1275 in the Perseus cluster as our exemplar. Assuming perfect knowledge of the instrument calibration, we show that a modest exposure (200 ks) of NGC 1275 by Athena permits us to exclude all photon–ALP couplings g a γ > 6.3 × 10−14 GeV−1 at the 95% confidence level, as previously shown by Conlon et al., representing a factor of 10 improvement over current limits. We then proceed to assess the impact of realistic calibration uncertainties on the Athena projection by applying a standard Cash likelihood procedure, showing the projected constraints on g a γ weaken by a factor of 10 (back to the current most sensitive constraints). However, we show how the use of a deep neural network can disentangle the energy-dependent features induced by instrumental miscalibration and those induced by photon–ALP mixing, allowing us to recover most of the sensitivity to the ALP physics. In our explicit demonstration, the machine learning applied allows us to exclude g a γ > 2.0 × 10−13 GeV−1, complementing the projected constraints of next-generation ALP dark matter birefringent cavity searches for very-light ALPs. Finally, we show that a 200 ks AXIS/on-axis observation of NGC 1275 will tighten the current best constraints on very-light ALPs by a factor of 3. [ABSTRACT FROM AUTHOR]

• Microinfusion delivers concentrated drugs IV at low flow rates with low flow carriers • Hemodynamic drugs may be formulated as emulsions; clevidipine is an example • Emulsion mixing properties may influence infusion delivery onset via microinfusion • Flow orientation influences emulsion delivery onset in microinfusion • Initial vertical up flow speeds, vertical down flow slows, emulsion delivery onset Critically ill and anesthetized patients commonly receive life-sustaining medications by pump-driven continuous intravenous infusion. Microinfusion refers to delivering concentrated drugs with low flow carriers to conserve fluid administration. Most infused medications are water-soluble. Delivery onset lag times have been identified for microinfusions of water-soluble drugs or experimental surrogates. Drugs may be formulated as emulsions. Initiation of emulsion microinfusions has not been described. We tested in vitro the hypothesis that an emulsion's physical characteristics would influence its microinfusion delivery onset. We adapted an established in vitro model of pump-driven continuous intravenous microinfusion to compare the delivery of methylene blue as a surrogate for water-soluble drugs and a 10% lipid emulsion as a surrogate for a drug formulated as an emulsion. The drug surrogates joined the carrier with carrier flow vertically upwards, vertically downwards or horizontally. We measured the times to 5%, 50% and 95% of plateau delivery. Emulsion entry into a vertical (upwards) carrier flow resulted in a rapid initial emulsion delivery exceeding predictions of delivery models. Emulsion entry into both horizontal and vertical (downwards) carrier flows resulted in long lag times to steady state. Methylene blue delivery was unaffected by carrier flow orientation. Initiating microinfusion emulsion delivery with upward flow can result in a relative bolus, whereas long delivery lags would be expected with horizontal or downwards flow. An emulsion might carry a high potency drug having significant physiologic effects, e. g. clevidipine. Unrecognized, differences in initial emulsion delivery kinetics depending on carrier flow orientation may have clinical implications for both efficacy and safety. [Display omitted] [ABSTRACT FROM AUTHOR]

It is increasingly recognized that effective and appropriate data sharing requires the development of models of good data-sharing practice capable of taking seriously both the potential benefits to be gained and the importance of ensuring that the rights and interests of participants are respected and that risk of harms is minimized. Calls for the greater sharing of individual-level data from biomedical and public health research are receiving support among researchers and research funders. Despite its potential importance, data sharing presents important ethical, social, and institutional challenges in low-income settings. In this article, we report on qualitative research conducted in five low- and middle-income countries exploring the experiences of key research stakeholders and their views about what constitutes good data-sharing practice. [ABSTRACT FROM AUTHOR]

Permanent childhood sensorineural hearing loss, is one of the most common birth defects in developed countries. It is important to identify the aetiology of hearing loss for many reasons, as there may be important health surveillance implications particularly with syndromic causes. Non-syndromic sensorineural hearing loss is a highly heterogeneous genetic condition, meaning that it may be caused by any one of numerous genes, with very few phenotypic distinctions between the different genetic types. This has previously presented significant challenges for genetic testing. However, the introduction of new technologies should enable more comprehensive testing in the future, bringing significant benefits to more affected children and their families. [ABSTRACT FROM AUTHOR]

Assessment and management of pain in pre-hospital care settings are important aspects of paramedic and clinical team roles. As emergency department waiting times and delays in paramedic-to-nurse handover increase, it becomes more and more vital that patients receive adequate pre-hospital pain relief. However, administration of analgesia can be inadequate and can result in patients experiencing oligoanalgesia, or under-treated pain. This article examines these issues along with the aetiology of trauma and the related socioeconomic background of traumatic injury. It reviews validated pain-assessment tools, outlines physiological responses to traumatic pain and discusses some of the misconceptions about the provision of effective analgesia in pre-hospital settings. [ABSTRACT FROM AUTHOR]

International guidelines stipulate that in order for children to participate in research, consent must be obtained from their parents or guardians. This is because researchers and ethics committee members have historically viewed children as vulnerable subjects. We, the authors of this article, think that in terms of decision-making for participation in medical research, children are not always vulnerable. Vulnerability is context- and study-specific. In this article, we argue that the blanket categorisation of children as vulnerable research subjects is ethically problematic. Significant numbers of mature minors, particularly in low-income settings, are currently being ruled out of research participation because their parents are unavailable or refuse to provide consent, despite the possibility that they might wish to do so and that such research has the potential to be of real benefit. Consequently, older children are under-represented in all types of clinical research. We here have illustrated our arguments using two case studies. In cases where research is important; meets international scientific and ethical standards and has been approved by relevant ethics committees; where the research team is trained to take consent; and where the information is presented in a way that is accessible to children, then children should sometimes be allowed to consent for themselves, rather than always being dependent on an adult. If children are able to provide valid consent to medical research in their own right, they should be allowed to do so, regardless of their age. The requirements for valid consent that we propose are competence, voluntariness, maturity, independence and contextual appropriateness. [ABSTRACT FROM AUTHOR]

Orchard floor vegetation competes with peach trees for water and nutrients and may harbor pathogens and insects. Tree growth, fruit yield, and fruit size can be optimized through management of vegetation in the tree row and irrigation. Under-tree vegetation-free strip widths (0, 0.6,1.2, 2.4,3.0, and 3.6 m) and irrigation were studied in years four through eight of a young peach orchard to determine their effects on peach tree growth and fruit yield, harvest maturity, and fruit size. Immature fruit samples were collected during thinning in years four through six to determine the effect of the treatments on the incidence of hemipteran (catfacing) insect damage. Trunk crosssectional area (TCSA), as a measure of tree growth, increased with increasing vegetationfree strip width; trees grown in the 3.6-m vegetation-free strip had TCSAs 2.2 times greater, on average, than trees grown in the 0-m vegetation-free strip. TCSA also increased with irrigation; trees grown with irrigation had TCSAs 1.2 times greater, on average, than trees grown without irrigation. Yield increased with increasing vegetationfree strip width, from 9.6 kg per tree in the 0-m plot to 26.5 kg per tree in the 3.6-m plot in year four, to 24.3 kg per tree in the 0-m plot and 39.6 kg per tree in the 3.6-m plot in year eight, for a total yield over years 4-8 per tree of 100 kg in the 0-m plot compared with 210 kg per tree in the 3.6-m plot. Yield, average fruit weight, and average fruit diameter increased with irrigation in three of 5 years; the other 2 years had higher than average rainfall reducing the need for supplemental irrigation. In 3 out of 5 years fruit in irrigated plots matured earlier than fruit in nonirrigated plots. In all years, fruit grown in the 0-m strip matured earliest and had the smallest diameter. Establishing a vegetationfree strip of as narrow as 0.6 m reduced the incidence of catfacing damage compared with the 0-m treatment, even though the orchard was on a commercial pesticide spray schedule. The least damage was seen with the industry standard vegetation-free strip widths greater than 3.0 m with or without irrigation. [ABSTRACT FROM AUTHOR]

Permanent childhood sensorineural hearing loss, is one of the most common birth defects in developed countries. It is important to identify the aetiology of hearing loss for many reasons, as there may be important health surveillance implications particularly with syndromic causes. Non-syndromic sensorineural hearing loss is a highly heterogeneous genetic condition, meaning that it may be caused by any one of numerous genes, with very few phenotypic distinctions between the different genetic types. This has previously presented significant challenges for genetic testing. However, the introduction of new technologies should enable more comprehensive testing in the future, bringing significant benefits to more affected children and their families. [ABSTRACT FROM AUTHOR]

BACKGROUND: Intravenous drug infusion driven by syringe pumps may lead to substantial temporal lags in achieving steady-state delivery at target levels when using very low flow rates ('microinfusion'). This study evaluated computer algorithms for reducing temporal lags via coordinated control of drug and carrier flows. METHODS: Novel computer control algorithms were developed based on mathematical models of fluid flow. Algorithm 1 controlled initiation of drug infusion and algorithm 2 controlled changes to ongoing steady-state infusions. These algorithms were tested in vitro and in vivo using typical high and low dead volume infusion system architectures. One syringe pump infused a carrier fluid and a second infused drug. Drug and carrier flowed together via a manifold through standard central venous catheters. Samples were collected in vitro for quantitative delivery analysis. Parameters including left ventricular max dP/dt were recorded in vivo. RESULTS: Regulation by algorithm 1 reduced delivery delay in vitro during infusion initiation by 69% (low dead volume) and 78% (high dead volume). Algorithmic control in vivo measuring % change in max dP/dt showed similar results (55% for low dead volume and 64% for high dead volume). Algorithm 2 yielded greater precision in matching the magnitude and timing of intended changes in vivo and in vitro. CONCLUSIONS: Compared with conventional methods, algorithm-based computer control of carrier and drug flows can improve drug delivery by pump-driven intravenous infusion to better match intent. For norepinephrine infusions, the amount of drug reaching the bloodstream per time appears to be a dominant factor in the hemodynamic response to infusion. [ABSTRACT FROM AUTHOR]

This paper engages with the question of what it is to 'do good medical ethics' in two ways. It begins with an exploration of what it might mean to say that health professionals practise good medical ethics as part of practising good ethical medicine. Using the example of the Genethics Club, a well-established national ethics forum for genetics professionals in the UK, the paper develops an account of moral craftsmanship grounded in the concepts of shared moral commitments and practices, moral work, ethics and living morality. In the light of this discussion, the paper goes on to consider what it might mean for a specialist in medical ethics, a bioethicist, to do good medical ethics. Finally, a research agenda focusing on the challenges of thinking about good medical ethics in a global context and a proposal for an innovative approach to bioethics methodology is outlined. [ABSTRACT FROM AUTHOR]

Biomedical research is an increasingly multidisciplinary activity bringing together a range of different academic fields and forms of expertise to investigate diseases that are increasingly understood to be complex and multifactorial. Recently the discipline of ethics has been starting to find a place in large-scale biomedical collaborations. In this article we draw from our experience of working with the Malaria Genomic Epidemiology Network (MalariaGEN) and other research projects to reflect upon the integration of ethics into biomedical research. We examine the way in which ethics input may be valuable to research, the forms it tends to take, and also the problems and limitations of such collaborations. [ABSTRACT FROM AUTHOR]

In this paper we employ the Shannon channel capacity theorem and classical thermodynamic Carnot's Law to derive the $kT\ln2$ minimum energy dissipation per bit for a communications channel. We then extend the analysis, incorporating forward error correction (FEC) to show an asymptotic energy efficiency approach to the Carnot/Shannon limit. For the first time, we derive a generalized version of the Shannon channel capacity theorem which embraces non-Gaussian noise statistics. Finally, we apply the theory to different telecommunications technologies, thus offering commonality of absolute energy efficiency assessment. [ABSTRACT FROM AUTHOR]

B Geometrical Thermodynamics b A new approach to physics, as described in article number 2100278, allows Mike Parker and co-workers to correctly calculate the sizes of the SP 4 sp He, SP 6 sp He, and SP 8 sp He nuclei ab initio from thermodynamics, with no quantum mechanics, inputting only the size of the proton. Halo Properties in Helium Nuclei from the Perspective of Geometrical Thermodynamics (Ann. The cover image illustrates the SP 8 sp He nucleus modelled as an alpha particle with its holomorphic 4-neutron halo. [Extracted from the article]

While the ribosome constitution is similar in all biota, there is a considerable increase in size of both ribosomal proteins (RPs) and RNAs in eukaryotes as compared to archaea and bacteria. This is pronounced in the large (60S) ribosomal subunit (LSU). In addition to enlargement (apparently maximized already in lower eukarya), the RP changes include increases in fraction, segregation and clustering of basic residues, and decrease in hydrophobicity. The acidic fraction is lower in eukaryote as compared to prokaryote RPs. In all eukaryote groups tested, the LSU RPs have significantly higher content of basic residues and homobasic segments than the SSU RPs. The vertebrate LSU RPs have much higher sequestration of basic residues than those of bacteria, archaea and even of the lower eukarya. The basic clusters are highly aligned in the vertebrate, but less in the lower eukarya, and only within families in archaea and bacteria. Increase in the basicity of RPs, besides helping transport to the nucleus, should promote stability of the assembled ribosome as well as the association with translocons and other intracellular matrix proteins. The size and GC nucleotide bias of the expansion segments of large LSU rRNAs also culminate in the vertebrate, and should support ribosome association with the endoplasmic reticulum and other intracellular networks. However, the expansion and nucleotide bias of eukaryote LSU rRNAs do not clearly correlate with changes in ionic parameters of LSU ribosomal proteins. [ABSTRACT FROM AUTHOR]

The status and use of transmembrane, extracellular and intracellular domains in oligomerization of heptahelical G-protein coupled receptors (GPCRs) are reviewed and for transmembrane assemblies also supplemented by new experimental evidence. The transmembrane-linked GPCR oligomers typically have as the minimal unit an asymmetric ~180 kDa pentamer consisting of receptor homodimer or heterodimer and a G-protein aß subunit heterotrimer. With neuropeptide Y (NPY) receptors, this assembly is converted to ~90 kDa receptor monomer-Ga complex by receptor and Ga agonists, and dimers/heteropentamers are depleted by neutralization of Gai subunits by pertussis toxin. Employing gradient centrifugation, quantification and other characterization of GPCR dimers at the level of physically isolated and identified heteropentamers is feasible with labeled agonists that do not dissociate upon solubilization. This is demonstrated with three neuropeptide Y (NPY) receptors and could apply to many receptors that use large peptidic agonists. [ABSTRACT FROM AUTHOR]

Background: To reduce financial barriers to access, and improve access to and use of skilled maternal and newborn healthcare services, the government of Ghana, in 2003, implemented a new maternal healthcare policy that provided free maternity care services in all public and mission healthcare facilities. Although supervised delivery in Ghana has increased from 47% in 2003 to 55% in 2010, strikingly high maternal mortality ratio and low percentage of skilled attendance are still recorded in many parts of the country. To explore health system factors that inhibit women's access to and use of skilled maternal and newborn healthcare services in Ghana despite these services being provided free. Methods: We conducted qualitative research with 185 expectant and lactating mothers and 20 healthcare providers in six communities in Ghana between November 2011 and May 2012. We used Attride-Stirling's thematic network analysis framework to analyze and present our data. Results: We found that in addition to limited and unequal distribution of skilled maternity care services, women's experiences of intimidation in healthcare facilities, unfriendly healthcare providers, cultural insensitivity, long waiting time before care is received, limited birthing choices, poor care quality, lack of privacy at healthcare facilities, and difficulties relating to arranging suitable transportation were important health system barriers to increased and equitable access and use of services in Ghana. Conclusion: Our findings highlight how a focus on patient-side factors can conceal the fact that many health systems and maternity healthcare facilities in low-income settings such as Ghana are still chronically under-resourced and incapable of effectively providing an acceptable minimum quality of care in the event of serious obstetric complications. Efforts to encourage continued use of maternity care services, especially skilled assistance at delivery, should focus on addressing those negative attributes of the healthcare system that discourage access and use. [ABSTRACT FROM AUTHOR]