A Brief History of Human Challenge Studies (1900-2021) Emphasising the Virology, Regulatory and Ethical Requirements, Raison D'etre, Ethnography, Selection of Volunteers and Unit Design.

Venetian quarantine 400 years ago was an important public health measure. Since 1900 this has been refined to include "challenge" or deliberate infection with pathogens be they viruses, bacteria, or parasites. Our focus is virology and ranges from the early experiments in Cuba with Yellow Fever Virus to the most widespread pathogen of our current times, COVID-19. The latter has so far caused over four million deaths worldwide and 190 million cases of the disease. Quarantine and challenge were also used to investigate the Spanish Influenza of 1918 which caused over 100 million deaths. We consider here the merits of the approach, that is the speeding up of knowledge in a practical sense leading to the more rapid licensing of vaccines and antimicrobials. At the core of quarantine and challenge initiatives is the design of the unit to allow safe confinement of the pathogen and protection of the staff. Most important though is the safety of volunteers. We can see now, as in 1900, that members of our society are prepared and willing to engage in these experiments for the public good. Our ethnology study, where the investigator observed the experiment from within the quarantine, gave us the first indication of changing attitudes amongst volunteers whilst in quarantine. These quarantine experiments, referred to as challenge studies, human infection studies, or "controlled human infection models" involve thousands of clinical samples taken over two to three weeks and can provide a wealth of immunological and molecular data on the infection itself and could allow the discovery of new targets for vaccines and therapeutics. The Yellow Fever studies from 121 years ago gave the impetus for development of a successful vaccine still used today whilst also uncovering the nature of the Yellow Fever agent, namely that it was a virus. We outline how carefully these experiments are approached and the necessity to have high quality units with self-contained air-flow along with extensive personal protective equipment for nursing and medical staff. Most important is the employment of highly trained scientific, medical and nursing staff. We face a future of emerging pathogens driven by the increasing global population, deforestation, climate change, antibiotic resistance and increased global travel. These emerging pathogens may be pathogens we currently are not aware of or have not caused outbreaks historically but could also be mutated forms of known pathogens including viruses such as influenza (H7N9, H5N1 etc.) and coronaviruses. This calls for challenge studies to be part of future pandemic preparedness as an additional tool to assist with the rapid development of broad-spectrum antimicrobials, immunomodulators and new vaccines.

A distinct neurogenomic response to a trade-off between social challenge and opportunity in male sticklebacks (Gasterosteus aculeatus).

Animals frequently make adaptive decisions about what to prioritize when faced with multiple, competing demands simultaneously. However, the proximate mechanisms of decision-making in the face of competing demands are not well understood. We explored this question using brain transcriptomics in a classic model system: threespined sticklebacks, where males face conflict between courtship and territorial defence. We characterized the behaviour and brain gene expression profiles of males confronted by a trade-off between courtship and territorial defence by comparing them to males not confronted by this trade-off. When faced with the trade-off, males behaviourally prioritized defence over courtship, and this decision was reflected in their brain gene expression profiles. A distinct set of genes and biological processes was recruited in the brain when males faced a trade-off and these responses were largely non-overlapping across two brain regions. Combined, these results raise new questions about the interplay between the neural and molecular mechanisms involved in decision-making.

Carriage of Staphylococcus pseudintermedius by clinically normal dogs in Canterbury, New Zealand.

AIMS: To investigate the frequency of carriage of methicillin-susceptible and methicillin-resistant Staphylococcus pseudintermedius (MRSP) in a population of clinically normal dogs within the Christchurch and wider Canterbury region, an area in which MRSP has been detected. METHODS: Buccal and perianal swabs were collected from 126 clinically normal dogs presenting at veterinary clinics in the Christchurch/Canterbury region for de-sexing or routine vaccination. S. pseudintermedius was isolated by selective culture. Isolates were tested for susceptibility to 12 antimicrobials by disc diffusion. RESULTS: S. pseudintermedius was isolated from 92/126 (73.0 (95% CI = 64.4-80.5)%) dogs, with 38/126 (30.2 (95% CI = 22.3-39.0)%) positive dogs carrying S. pseudintermedius at both sampled sites. More animals (78/126; 61.9 (95% CI = 52.8-70.4)%) had positive mouth cultures than positive perianal region cultures (52/126; 41.3 (95% CI = 32.6-50.4)%). No MRSP was isolated from clinically normal dogs. However, resistance to penicillin (106/130 (85.1%) swabs) and tetracycline (33/130 (25.4%) swabs) was seen. CONCLUSIONS: The majority of the dogs in this sample were carriers of S. pseudintermedius. However, none of these isolates were MRSP. CLINICAL RELEVANCE: While most clinically normal dogs in the studied region are likely to be carriers of S. pseudintermedius, only a small proportion, if any, are likely to be carriers of MRSP. Antibiotic stewardship practices may be important to maintain low-level circulation of drug-resistant bacterial lineages.

Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device - the SERCA-LVAD TRIAL.

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.

Absence of Low-Energy Shape Coexistence in

The ^{80}Ge structure was investigated in a high-statistics ß-decay experiment of ^{80}Ga using the GRIFFIN spectrometer at TRIUMF-ISAC through γ, ß-e, e-γ, and γ-γ spectroscopy. No evidence was found for the recently reported 0_{2}^{+} 639-keV level suggested as evidence for low-energy shape coexistence in ^{80}Ge. Large-scale shell model calculations performed in ^{78,80,82}Ge place the 0_{2}^{+} level in ^{80}Ge at 2 MeV. The new experimental evidence combined with shell model predictions indicate that low-energy shape coexistence is not present in ^{80}Ge.

Use of Hologic LOCalizer radiofrequency identification (RFID) tags to localise impalpable breast lesions and axillary nodes: experience of the first 150 cases in a UK breast unit.

AIM: To report the outcome of 150 patients using the Hologic LOCalizer RFID (radiofrequency identification) tag system, including the first reported use of RFID tags in the axilla. MATERIALS AND METHODS: Data were collected prospectively from the first tag insertion (12 June 2019) until 150 consecutive patients had undergone surgery (excision date 9 January 2020). RESULTS: A total of 177 tags were targeted to 177 malignant lesions in 150 women. Tags were inserted an average of 7.8 days before surgery (range 0-71 days). One hundred and twenty-six tags were targeted to a single lesion in one breast only; the remainder of tags were targeted to multiple lesions in one or both breasts, as well as to axillary lymph nodes. In addition, two cases involved the use of two tags to bracket microcalcification. All except three tags were satisfactorily deployed at their initial intended target. The majority of target lesions were masses (n=142, mean size 13.8 mm), with a range of other targets including post-vacuum-assisted biopsy cavities, marker clips post-neoadjuvant chemotherapy, architectural distortions, and clipped metastatic lymph nodes. All tags were successfully retrieved at surgical excision. Re-excision rate was 8.7%. There were no tag-specific surgical complications. CONCLUSIONS: The RFID tag system demonstrates many advantages over guidewires, and is effective at targeting axillary lymph nodes and multiple sites within the same breast.

A descriptive analysis of an outbreak of measles and a multilevel mixed-effects analysis of factors associated with case isolation in healthcare settings, London (February-June 2016).

OBJECTIVES: We described the epidemiology and healthcare exposures during a measles outbreak in London and identified factors associated with isolation on arrival to healthcare premises. STUDY DESIGN: We conducted a cohort study including all confirmed measles cases in London residents from February 1, 2016, to June 30, 2016, and semistructured interviews with two infection prevention and control teams (IPCTs). METHODS: We described the outbreak and conducted a multilevel mixed-effects analysis to assess the relationship between sociodemographic and clinical factors and isolation on arrival to healthcare premises. We summarised the interviews. RESULTS: There were 182 cases, mostly aged 17-35 years (46%; 84). Excluding cases younger than one year, 76% (92/120) were unvaccinated, including two healthcare workers. The majority presented with rash (97%; 174), and 42% (70/166) required hospitalisation. Of the recorded cases, 93% of cases (164/178) had visited a healthcare setting during their infectious period (median number of visits = 2). In 33% (59/178) of the visits, the case was isolated on arrival; when not isolated, four healthcare exposures resulted in further transmission. Presenting to the hospital as opposed to a general practitioner (GP) was associated with higher odds of isolation (odds ratio = 2.23, 95% confidence interval = 1.1-4.4) when adjusted for age, gender and presenting with a cough. The IPCT identified measles training using standardised risk assessments by triage nurses in accident and emergency and intelligence regarding measles activity in the community as positive measures to prevent healthcare exposures. CONCLUSIONS: We recommend opportunistic immunisation of unvaccinated young adults by GPs and that occupational health departments ensure their staff are protected against measles. Raising measles awareness in healthcare settings via training or regular sharing of current measles surveillance activity from public health to the IPCT and GP may improve triage and isolation of cases on arrival to healthcare premises.

Magnetic Entropy as a Proposed Gating Mechanism for Magnetogenetic Ion Channels.

Magnetically sensitive ion channels would allow researchers to better study how specific brain cells affect behavior in freely moving animals; however, recent reports of "magnetogenetic" ion channels based on biogenic ferritin nanoparticles have been questioned because known biophysical mechanisms cannot explain experimental observations. Here, we reproduce a weak magnetically mediated calcium response in HEK cells expressing a previously published TRPV4-ferritin fusion protein. We find that this magnetic sensitivity is attenuated when we reduce the temperature sensitivity of the channel but not when we reduce the mechanical sensitivity of the channel, suggesting that the magnetic sensitivity of this channel is thermally mediated. As a potential mechanism for this thermally mediated magnetic response, we propose that changes in the magnetic entropy of the ferritin particle can generate heat via the magnetocaloric effect and consequently gate the associated temperature-sensitive ion channel. Unlike other forms of magnetic heating, the magnetocaloric mechanism can cool magnetic particles during demagnetization. To test this prediction, we constructed a magnetogenetic channel based on the cold-sensitive TRPM8 channel. Our observation of a magnetic response in cold-gated channels is consistent with the magnetocaloric hypothesis. Together, these new data and our proposed mechanism of action provide additional resources for understanding how ion channels could be activated by low-frequency magnetic fields.

Incidence, causes and correlates of maternal near-miss morbidity: a multi-centre cross-sectional study.

OBJECTIVE: To explore the incidence and factors associated with maternal near-miss. DESIGN: Cross-sectional study with an embedded case-control study. SETTING: Three tertiary referral hospitals in southern Ghana. POPULATION: All women admitted to study facilities with pregnancy-related complications or for birth. METHODS: An adapted version of the WHO Maternal Near Miss Screening Tool was used to identify maternal near-miss cases. These were compared with unmatched controls (uncomplicated deliveries) in a ratio of 1:2. MAIN OUTCOME MEASURES: Incidence of maternal near-miss, maternal near-miss to maternal mortality ratio, and cause of and factors associated with maternal near-miss. RESULTS: Out of 8433 live births, 288 maternal near-miss cases and 62 maternal deaths were identified. In all, 454 healthy controls were recruited for comparison. Maternal near-miss and maternal death incidence ratios were 34.2 (95% CI 30.2-38.1) and 7.4 (95% CI 5.5-9.2) per 1000 live births, respectively with a maternal near-miss to mortality ratio of 4.6:1. Cause of near-miss was pre-eclampsia/eclampsia (41.0%), haemorrhage (12.2%), maternal sepsis (11.1%) and ruptured uterus (4.2%). A major factor associated with maternal near-miss was maternal fever within the 7 days before birth (OR 5.95, 95%CI 3.754-9.424). Spontaneous onset of labour was protective against near-miss (OR 0.09 95% CI 0.057-0.141). CONCLUSION: For every maternal death, there were nearly five maternal near-misses. Women having a fever in the 7 days before delivery were six times more likely to experience a near-miss than women not having fever. TWEETABLE ABSTRACT: Maternal near-miss exceeds maternal death by 5:1, with the leading cause of maternal near-miss was pre-eclampsia/eclampsia.

The birth experience and subsequent maternal caregiving attitudes and behavior: a birth cohort study.

Optimal maternal caregiving is critical for children's healthy development, yet quality of maternal caregiving may be influenced by a negative birth experience. We examined whether the birth experience was associated with maternal caregiving attitudes and behavior throughout the first year. We conducted secondary analysis of the Avon Longitudinal Study of Parents and Children birth cohort on perinatal data. The birth experience was assessed using self-report data on level of support in labor. Maternal caregiving variables were self-report maternal attitudes at one and eight postnatal months, and observed maternal behavior at 12 postnatal months. Data were analyzed using multivariable logistic regression models adjusting for critical covariates at one (N = 4389), eight (N = 4580), and 12 (N = 842) postnatal months. Feeling supported in labor was associated with a report of "immediately falling in love" with one's baby after birth, surveyed at 1 month (adjusted OR 1.41 [95% CI 1.20-1.65]), and with more positive parenting scores at 8 months (adjusted OR 1.56 [95% CI 1.36-1.79]), but not with more positive observed maternal behavior at 12 months. Additional risk factors were identified. Our findings suggest that we may be able to modify the risk of poor postnatal maternal caregiving by supporting women in labor and facilitating a positive birth experience.

One Health operations: a critical component in the International Health Regulations Monitoring and Evaluation Framework.

Under the International Health Regulations (IHR, 2005), a legally binding document adopted by 196 States Parties, countries are required to develop their capacity to rapidly detect, assess, notify and respond to unusual health events of potential international concern. To support countries in monitoring and enhancing their capacities and complying with the IHR (2005), the World Health Organization (WHO) developed the IHR Monitoring and Evaluation Framework (IHR MEF). This framework comprises four complementary components: the State Party Annual Report, the Joint External Evaluation, after-action reviews and simulation exercises. The first two are used to review capacities and the second two to help to explore their functionality. The contribution of different disciplines, sectors, and areas of work, joining forces through a One Health approach, is essential for the implementation of the IHR (2005). Therefore, WHO, in partnership with the Food and Agriculture Organization of the United Nations (FAO), the World Organisation for Animal Health (OIE), and other international and national partners, has actively worked on facilitating the inclusion of the relevant sectors, in particular the animal health sector, in each of the four components of the IHR MEF. Other tools complement the IHR MEF, such as the WHO/OIE IHR-PVS [Performance of Veterinary Services] National Bridging Workshops, which facilitate the optimal use of the results of the IHR MEF and the OIE Performance of Veterinary Services Pathway and create an opportunity for stakeholders from animal health and human health services to work on the coordination of their efforts. The results of these various tools are used in countries' planning processes and are incorporated in their National Action Plan for Health Security to accelerate the implementation of IHR core capacities. The present article describes how One Health is incorporated in all components of the IHR MEF.

En vertu du Règlement sanitaire international (RSI, 2005), instrument juridique ayant force obligatoire pour les 196 États Parties dans le monde, les pays s'engagent à renforcer leurs capacités de détection, d'évaluation, de notification et de réaction en cas d'événements sanitaires inhabituels ou présentant une dimension internationale inquiétante. Le Cadre de suivi et d'évaluation du RSI (2005) a été élaboré par l'Organisation mondiale de la santé (OMS) afin de soutenir les pays souhaitant évaluer et améliorer leurs capacités et leur niveau de conformité avec le RSI (2005). Ce cadre comprend quatre composantes complémentaires : le rapport annuel de l'État Partie, l'Évaluation extérieure conjointe, les examens « après action¼ et les exercices de simulation. Les deux premières composantes permettent de faire le point sur les capacités tandis que les deux dernières visent une connaissance détaillée de leur fonctionnement. La mise en oeuvre du RSI (2005) demande aux différentes disciplines, secteurs et domaines d'activités de fédérer leurs forces dans une approche Une seule santé. Par conséquent, en partenariat avec l'Organisation des Nations Unies pour l'alimentation et l'agriculture (FAO), avec l'Organisation mondiale de la santé animale (OIE) et avec d'autres partenaires internationaux et nationaux, l'OMS a fait en sorte de faciliter l'intégration de tous les secteurs concernés, en particulier celui de la santé animale, dans les diverses composantes du Cadre d'évaluation du RSI. D'autres outils complètent celui-ci, en particulier les ateliers de liaison nationaux OMS/OIE sur le RSI et le Processus d'évaluation des performances des Services vétérinaires (PVS), dont le but est de faciliter l'utilisation optimale des résultats du Cadre d'évaluation du RSI et du Processus PVS de l'OIE et de fournir aux acteurs des services de santé animale et de santé publique la possibilité de se concerter sur les modalités d'une synergie de leur action. Les résultats de ces outils sont ensuite pris en compte par les pays lors des procédures de planification et intégrés dans les Plans d'action nationaux pour la sécurité sanitaire afin d'accélérer la mise en oeuvre des capacités fondamentales décrites dans le RSI. Les auteurs décrivent l'intégration du concept Une seule santé dans chacune des composantes du Cadre d'évaluation du RSI.

Según lo dispuesto en el Reglamento Sanitario Internacional (RSI, 2005), documento jurídicamente vinculante suscrito por 196 Estados Partes, los países están obligados a dotarse de la capacidad necesaria para detectar, evaluar, notificar y afrontar con rapidez todo evento sanitario inusual que pueda revestir importancia internacional. Para ayudar a los países a dotarse de mejores capacidades, a seguir de cerca su evolución al respecto y a dar cumplimiento al RSI (2005), la Organización Mundial de la Salud (OMS) elaboró el marco de seguimiento y evaluación del RSI, que consta de cuatro elementos complementarios: el informe anual que debe presentar cada Estado Parte; la evaluación externa conjunta; exámenes posteriores a las intervenciones; y ejercicios de simulación. Los dos primeros sirven para examinar las capacidades, y los dos segundos para ayudar a estudiar su funcionalidad. Para la aplicación del RSI (2005) es fundamental la contribución de diferentes disciplinas, sectores y ámbitos de trabajo, que aúnen esfuerzos actuando desde los postulados de Una sola salud. Por ello la OMS, en colaboración con la Organización de las Naciones Unidas para la Alimentación y la Agricultura (FAO), la Organización Mundial de Sanidad Animal (OIE) y otros asociados internacionales y nacionales, ha trabajado activamente para facilitar la integración de los sectores pertinentes, en particular el de la sanidad animal, en cada uno de los cuatro componentes del marco de seguimiento y evaluación del RSI. Hay otros dispositivos que vienen a complementar este marco, por ejemplo los talleres nacionales dedicados a la creación de nexos entre el RSI y el proceso PVS (Prestaciones de los Servicios Veterinarios) de la OIE, organizados conjuntamente por la OMS y la OIE, que facilitan un uso idóneo de los resultados del marco de seguimiento y evaluación del RSI y del proceso PVS y brindan a las partes interesadas de los servicios sanitarios y zoosanitarios la oportunidad de trabajar sobre la coordinación de sus respectivas actividades. Los resultados de estas diversas herramientas alimentan después los procesos de planificación de los países y son incorporados a su Plan de acción nacional de seguridad sanitaria para acelerar la implantación de las capacidades básicas prescritas en el RSI. Los autores explican cómo se incorpora la filosofía de Una sola salud a todos los componentes del marco de seguimiento y evaluación del RSI.

Silicon-Based Optical Mirror Coatings for Ultrahigh Precision Metrology and Sensing.

Thermal noise of highly reflective mirror coatings is a major limit to the sensitivity of many precision laser experiments with strict requirements such as low optical absorption. Here, we investigate amorphous silicon and silicon nitride as an alternative to the currently used combination of coating materials, silica, and tantala. We demonstrate an improvement by a factor of ≈55 with respect to the lowest so far reported optical absorption of amorphous silicon at near-infrared wavelengths. This reduction was achieved via a combination of heat treatment, final operation at low temperature, and a wavelength of 2 µm instead of the more commonly used 1550 nm. Our silicon-based coating offers a factor of 12 thermal noise reduction compared to the performance possible with silica and tantala at 20 K. In gravitational-wave detectors, a noise reduction by a factor of 12 corresponds to an increase in the average detection rate by three orders of magnitude (≈12^{3}).

Amorphous Silicon with Extremely Low Absorption: Beating Thermal Noise in Gravitational Astronomy.

Amorphous silicon has ideal properties for many applications in fundamental research and industry. However, the optical absorption is often unacceptably high, particularly for gravitational-wave detection. We report a novel ion-beam deposition method for fabricating amorphous silicon with unprecedentedly low unpaired electron-spin density and optical absorption, the spin limit on absorption being surpassed for the first time. At low unpaired electron density, the absorption is no longer correlated with electron spins, but with the electronic mobility gap. Compared to standard ion-beam deposition, the absorption at 1550 nm is lower by a factor of ≈100. This breakthrough shows that amorphous silicon could be exploited as an extreme performance optical coating in near-infrared applications, and it represents an important proof of concept for future gravitational-wave detectors.

Predicting suicides after outpatient mental health visits in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS).

The 2013 US Veterans Administration/Department of Defense Clinical Practice Guidelines (VA/DoD CPG) require comprehensive suicide risk assessments for VA/DoD patients with mental disorders but provide minimal guidance on how to carry out these assessments. Given that clinician-based assessments are not known to be strong predictors of suicide, we investigated whether a precision medicine model using administrative data after outpatient mental health specialty visits could be developed to predict suicides among outpatients. We focused on male nondeployed Regular US Army soldiers because they account for the vast majority of such suicides. Four machine learning classifiers (naive Bayes, random forests, support vector regression and elastic net penalized regression) were explored. Of the Army suicides in 2004-2009, 41.5% occurred among 12.0% of soldiers seen as outpatient by mental health specialists, with risk especially high within 26 weeks of visits. An elastic net classifier with 10-14 predictors optimized sensitivity (45.6% of suicide deaths occurring after the 15% of visits with highest predicted risk). Good model stability was found for a model using 2004-2007 data to predict 2008-2009 suicides, although stability decreased in a model using 2008-2009 data to predict 2010-2012 suicides. The 5% of visits with highest risk included only 0.1% of soldiers (1047.1 suicides/100 000 person-years in the 5 weeks after the visit). This is a high enough concentration of risk to have implications for targeting preventive interventions. An even better model might be developed in the future by including the enriched information on clinician-evaluated suicide risk mandated by the VA/DoD CPG to be recorded.

Expected background rates of latent TB infection in London inner city schools: lessons from a TB contact investigation exercise in a secondary school.

Following an extensive contact tracing exercise at a school in a London borough with one of highest tuberculosis (TB) rates in England, we estimated the background prevalence of latent TB infection to be significantly less than the widely accepted 10%. We screened 271 pupils aged 14-15 years in two groups: 96 pupils in group 1 had significant exposure (>8 h/week in the same room) to a case of infectious TB and 175 in group 2 who had minimal exposure. In group 1, 26% were diagnosed with latent or active TB, compared to 6.3% in group 2. Risk factors for TB infection (e.g. previous exposure or link to high-prevalence communities) were analysed using a cohort study design. In the univariable analysis only being in contact group 1 was statistically significantly associated with being a case (OR 5.25, 95%, P < 0.001). In the multivariable model contact group 1 remained significantly associated with being a case (adjusted OR 4.40, P = 0.001). We concluded that the 6.3% yield of TB infection in contact group 2 is either similar to or higher than the background prevalence rate of latent TB infection (LTBI) in this high TB prevalence London borough. Other parts of England with lower TB prevalence are likely to have even lower LTBI rates.

Generation of scaled protogalactic seed magnetic fields in laser-produced shock waves.

The standard model for the origin of galactic magnetic fields is through the amplification of seed fields via dynamo or turbulent processes to the level consistent with present observations. Although other mechanisms may also operate, currents from misaligned pressure and temperature gradients (the Biermann battery process) inevitably accompany the formation of galaxies in the absence of a primordial field. Driven by geometrical asymmetries in shocks associated with the collapse of protogalactic structures, the Biermann battery is believed to generate tiny seed fields to a level of about 10(-21) gauss (refs 7, 8). With the advent of high-power laser systems in the past two decades, a new area of research has opened in which, using simple scaling relations, astrophysical environments can effectively be reproduced in the laboratory. Here we report the results of an experiment that produced seed magnetic fields by the Biermann battery effect. We show that these results can be scaled to the intergalactic medium, where turbulence, acting on timescales of around 700 million years, can amplify the seed fields sufficiently to affect galaxy evolution.

Point Prevalence of Adult Intestinal Failure in Republic Of Ireland.

Parenteral Nutrition (PN) is a life-saving treatment used for patients with Intestinal Failure (IF). PN is complex and demands highly specialised care to avoid serious complications in the home setting. All tertiary centres in the Republic of Ireland (ROI) were contacted to assess the prevalence of IF requiring PN and complications, over a one year period. Sixty-seven patients were treated across 15 centres: a period prevalence of 14.6 and 9.6 patients per million for long-term PN and home PN respectively. Three-quarters of patients experienced at least one major complication with 18% mortality rate over the study period. There were 2.86 admissions per HPN patient, each lasting mean 13.4 days. One-third experienced catheter-related infections. There was a reduced length of stay during emergency re-admissions in high volume centres (mean 31 v 43 days, p=0.17). The establishment of a National Centre for IF/HPN in ROI is integral to reducing PN-associated complications.

What can dental education gain by understanding student experience of the curriculum?

INTRODUCTION: Within higher education, there is increasing recognition that understanding the ways students experience the educational environment is critical to developing programmes that can educate our future professionals. There is a small body of literature about how students experience the dental educational environment; however, none that adopts a qualitative phenomenographic approach. This study aims to contribute to our understanding by asking what is the variation in the ways dental students experience their curriculum? METHODS: This study uses a phenomenographic methodology. Phenomenography investigates the variation in the way a group of people experience a situation, and how they ascribe meaning to it. Interviews were conducted with 14 senior dental students at the University of Sydney. Transcripts were analysed using a phenomenographic approach. RESULTS: Six increasingly sophisticated, qualitatively distinct categories of description were identified from the collective of transcripts: surviving the education system; following a guide or manual, learning how to treat teeth, learning how to meet patient treatment needs, learning how to relate with patients and understanding the complexities of dental practice. The outcome space consists of ways the categories of description are related; considering interactions with teachers, ways of coping with multiple opinions and integration of disciplinary learning. CONCLUSION: This study provides new insights into the multifaceted and relational ways that dental students experience their educational environment. It could point curriculum designers towards strategies that assist students develop sophisticated understandings about themselves as practitioners, patients and the complexities of dental practice. Suggestions about the practical implications of the findings of this research are given.

First Demonstration of Electrostatic Damping of Parametric Instability at Advanced LIGO.

Interferometric gravitational wave detectors operate with high optical power in their arms in order to achieve high shot-noise limited strain sensitivity. A significant limitation to increasing the optical power is the phenomenon of three-mode parametric instabilities, in which the laser field in the arm cavities is scattered into higher-order optical modes by acoustic modes of the cavity mirrors. The optical modes can further drive the acoustic modes via radiation pressure, potentially producing an exponential buildup. One proposed technique to stabilize parametric instability is active damping of acoustic modes. We report here the first demonstration of damping a parametrically unstable mode using active feedback forces on the cavity mirror. A 15 538 Hz mode that grew exponentially with a time constant of 182 sec was damped using electrostatic actuation, with a resulting decay time constant of 23 sec. An average control force of 0.03 nN was required to maintain the acoustic mode at its minimum amplitude.

Individual Differences in the Alignment of Structural and Functional Markers of the V5/MT Complex in Primates.

Extrastriate visual area V5/MT in primates is defined both structurally by myeloarchitecture and functionally by distinct responses to visual motion. Myelination is directly identifiable from postmortem histology but also indirectly by image contrast with structural magnetic resonance imaging (sMRI). First, we compared the identification of V5/MT using both sMRI and histology in Rhesus macaques. A section-by-section comparison of histological slices with in vivo and postmortem sMRI for the same block of cortical tissue showed precise correspondence in localizing heavy myelination for V5/MT and neighboring MST. Thus, sMRI in macaques accurately locates histologically defined myelin within areas known to be motion selective. Second, we investigated the functionally homologous human motion complex (hMT+) using high-resolution in vivo imaging. Humans showed considerable intersubject variability in hMT+ location, when defined with myelin-weighted sMRI signals to reveal structure. When comparing sMRI markers to functional MRI in response to moving stimuli, a region of high myelin signal was generally located within the hMT+ complex. However, there were considerable differences in the alignment of structural and functional markers between individuals. Our results suggest that variation in area identification for hMT+ based on structural and functional markers reflects individual differences in human regional brain architecture.