High-power Raman lasing and efficient anti-Stokes generation in mm-sized crystalline disk resonators.

We have previously experimentally observed high-power Stokes and second-order Stokes output from a mm-sized CaF2 disk using stimulated Raman scattering. A pump laser at a wavelength of 1.06 µm was coupled via a tapered fiber to the whispering gallery modes (WGM) of the disk. In this Letter, we extend this work and demonstrate the production of the first anti-Stokes sideband at power levels as high as 60 µW in near continuous-wave (CW) operation. The result is a four-component Raman comb at the output, with a wavelength range covering from 1.023 to 1.14 µm. We discuss the threshold dependence of the observed Raman lines on the crystal orientation and provide experimental validation. These advances enable the use of such mm-sized resonators as compact, efficient sources for terahertz-level frequency modulation.

A national survey investigating the impact of the COVID-19 pandemic on core and higher breast radiology training in the UK.

AIM: To investigate the impact of the COVID-19 pandemic on core and higher breast radiology training in the UK from the perspective of trainees and new consultants. MATERIALS AND METHODS: A survey comprising 25 questions was distributed to UK radiology trainees via the regional Junior Radiologists Forum representatives under the auspices of the British Society of Breast Radiology (BSBR). RESULTS: Sixty-nine eligible responses were received representing all UK training regions. Fifty-five per cent of respondents completing either a core or higher breast rotation felt that the pandemic had a negative effect on their breast training. There was an overall reduction in exposure to the key breast imaging methods when rotations took place during the pandemic. Completing a core breast rotation during the pandemic was less likely to attract trainees to higher breast training. Three out of four breast radiology consultants in their first year after receiving their Certificate of Completion of Training (CCT) felt the pandemic reduced their preparedness for becoming consultants. Positive outcomes included the increased use of online educational resources and remote multidisciplinary meetings. CONCLUSIONS: As well as having a negative impact on breast radiology training overall, the pandemic has had a detrimental effect on attracting trainees to breast radiology as a future career. It is of key importance that trainees have a positive core breast rotation as this experience appears central to many trainees' decisions to pursue higher breast training. Increased use of online learning resources has also been positively received and is a valuable approach to learning that can be maintained in the longer term.

Evaluating the performance of temporal and spatial early warning statistics of algal blooms.

Regime shifts have large consequences for ecosystems and the services they provide. However, understanding the potential for, causes of, proximity to, and thresholds for regime shifts in nearly all settings is difficult. Generic statistical indicators of resilience have been proposed and studied in a wide range of ecosystems as a method to detect when regime shifts are becoming more likely without direct knowledge of underlying system dynamics or thresholds. These early warning statistics (EWS) have been studied separately but there have been few examples that directly compare temporal and spatial EWS in ecosystem-scale empirical data. To test these methods, we collected high-frequency time series and high-resolution spatial data during a whole-lake fertilization experiment while also monitoring an adjacent reference lake. We calculated two common EWS, standard deviation and autocorrelation, in both time series and spatial data to evaluate their performance prior to the resulting algal bloom. We also applied the quickest detection method to generate binary alarms of resilience change from temporal EWS. One temporal EWS, rolling window standard deviation, provided advanced warning in most variables prior to the bloom, showing trends and between-lake patterns consistent with theory. In contrast, temporal autocorrelation and both measures of spatial EWS (spatial SD, Moran's I) provided little or no warning. By compiling time series data from this and past experiments with and without nutrient additions, we were able to evaluate temporal EWS performance for both constant and changing resilience conditions. True positive alarm rates were 2.5-8.3 times higher for rolling window standard deviation when a lake was being pushed towards a bloom than the rate of false positives when it was not. For rolling window autocorrelation, alarm rates were much lower and no variable had a higher true positive than false positive alarm rate. Our findings suggest temporal EWS provide advanced warning of algal blooms and that this approach could help managers prepare for and/or minimize negative bloom impacts.

Operationalising coastal resilience to flood and erosion hazard: A demonstration for England.

Resilience is widely seen as an important attribute of coastal systems and, as a concept, is increasingly prominent in policy documents. However, there are conflicting ideas on what constitutes resilience and its operationalisation as an overarching principle of coastal management remains limited. In this paper, we show how resilience to coastal flood and erosion hazard could be measured and applied within policy processes, using England as a case study. We define resilience pragmatically, integrating what is presently a disparate set of policy objectives for coastal areas. Our definition uses the concepts of resistance, recovery and adaptation, to consider how the economic, social and environmental dimensions of coastal systems respond to change. We develop a set of composite indicators for each dimension, grounded empirically with reference to national geospatial datasets. A prototype Coastal Resilience Model (CRM) has been developed, which combines the dimensions and generates a quantitative resilience index. We apply it to England's coastal hazard zone, capturing a range of different stakeholder perspectives using relative indicator weightings. The illustrative results demonstrate the practicality of formalising and quantifying resilience. To re-focus national policy around the stated desire of enhancing resilience to coastal flooding and erosion would require firm commitment from government to monitor progress towards resilience, requiring extension of the present risk-based approach, and a consensus methodology in which multiple (and sometimes conflicting) stakeholder values are explicitly considered. Such a transition may also challenge existing governance arrangements at national and local levels, requiring incentives for coastal managers to engage with and apply this new approach, more departmental integration and inter-agency cooperation. The proposed Coastal Resilience Model, with the tools to support planning and measure progress, has the potential to help enable this transition.

Host exposure history and priority effects impact the development and reproduction of a dominant parasite.

Within a single organism, numerous parasites often compete for space and resources. This competition, together with a parasite's ability to locate and successfully establish in a host, can contribute to the distribution and prevalence of parasites. Coinfection with trematodes in snail intermediate hosts is rarely observed in nature, partly due to varying competitive abilities among parasite taxa. Using a freshwater snail host (Biomphalaria glabrata), we studied the ability of a competitively dominant trematode, Echinostoma caproni, to establish and reproduce in a host previously infected with a less competitive trematode species, Schistosoma mansoni. Snails were exposed to S. mansoni and co-exposed to E. caproni either simultaneously or 1 week, 4 weeks, or 6 weeks post S. mansoni exposure. Over the course of infection, we monitored the competitive success of the dominant trematode through infection prevalence, parasite development time, and parasite reproductive output. Infection prevalence of E. caproni did not differ among co-exposed groups or between co-exposed and single exposed groups. However, E. caproni infections in co-exposed hosts took longer to reach maturity when the timing between co-exposures increased. All co-exposed groups had higher E. caproni reproductive output than single exposures. We show that although timing of co-exposure affects the development time of parasite transmission stages, it is not important for successful establishment. Additionally, co-exposure, but not priority effects, increases the reproductive output of the dominant parasite.

Anatomy and resilience of the global production ecosystem.

Much of the Earth's biosphere has been appropriated for the production of harvestable biomass in the form of food, fuel and fibre. Here we show that the simplification and intensification of these systems and their growing connection to international markets has yielded a global production ecosystem that is homogenous, highly connected and characterized by weakened internal feedbacks. We argue that these features converge to yield high and predictable supplies of biomass in the short term, but create conditions for novel and pervasive risks to emerge and interact in the longer term. Steering the global production ecosystem towards a sustainable trajectory will require the redirection of finance, increased transparency and traceability in supply chains, and the participation of a multitude of players, including integrated 'keystone actors' such as multinational corporations.

Livestock host composition rather than land use or climate explains spatial patterns in bluetongue disease in South India.

Culicoides-borne arboviruses of livestock impair animal health, livestock production and livelihoods worldwide. As these arboviruses are multi-host, multi-vector systems, predictions to improve targeting of disease control measures require frameworks that quantify the relative impacts of multiple abiotic and biotic factors on disease patterns. We develop such a framework to predict long term (1992-2009) average patterns in bluetongue (BT), caused by bluetongue virus (BTV), in sheep in southern India, where annual BT outbreaks constrain the livelihoods and production of small-holder farmers. In Bayesian spatial general linear mixed models, host factors outperformed landscape and climate factors as predictors of disease patterns, with more BT outbreaks occurring on average in districts with higher densities of susceptible sheep breeds and buffalo. Since buffalo are resistant to clinical signs of BT, this finding suggests they are a source of infection for sympatric susceptible sheep populations. Sero-monitoring is required to understand the role of buffalo in maintaining BTV transmission and whether they must be included in vaccination programs to protect sheep adequately. Landscape factors, namely the coverage of post-flooding, irrigated and rain-fed croplands, had weak positive effects on outbreaks. The intimate links between livestock host, vector composition and agricultural practices in India require further investigation at the landscape scale.

Nitric oxide activation facilitated by cooperative multimetallic electron transfer within an iron-functionalized polyoxovanadate-alkoxide cluster.

A series of NO-bound, iron-functionalized polyoxovanadate-alkoxide (FePOV-alkoxide) clusters have been synthesized, providing insight into the role of multimetallic constructs in the coordination and activation of a substrate. Upon exposure of the heterometallic cluster to NO, the vanadium-oxide metalloligand is oxidized by a single electron, shuttling the reducing equivalent to the {FeNO} subunit to form a {FeNO}7 species. Four NO-bound clusters with electronic distributions ranging from [VV3VIV2]{FeNO}7 to [VIV5]{FeNO}7 have been synthesized, and characterized via 1H NMR, infrared, and electronic absorption spectroscopies. The ability of the FePOV-alkoxide cluster to store reducing equivalents in the metalloligand for substrate coordination and activation highlights the ultility of the metal-oxide scaffold as a redox reservoir.

Prophylactic bypassing agent use before and during immune tolerance induction in patients with haemophilia A and inhibitors to FVIII.

The development of high-titre inhibitory antibodies (inhibitors) against factor VIII (FVIII) remains a challenge in the management of patients with haemophilia A (HA). Patients with high-titre inhibitors are more likely to experience uncontrolled bleeding, physical disability from chronic arthropathy and premature death compared with those without this complication. Immune tolerance induction (ITI), utilizing repeated infusions of FVIII, is an effective therapeutic approach to eliminating inhibitory antibodies. This strategy can eradicate FVIII inhibitors, so that FVIII-specific tolerance is induced. However, patients undergoing ITI are still vulnerable to the development of serious and/or repeated bleeding events. The efficacy of bypassing agents in preventing bleeding episodes has been widely proven in patients with HA and inhibitors to FVIII. Evidence suggests that reducing bleeding during ITI can also shorten the time to tolerance. There are concerns with the use of bypassing agents, including the cost of treatment, short half-life, management of non-responders and the risk of thrombosis. Despite these concerns, and the still limited evidence from prospective studies and consensus reports, the use of prophylaxis with bypassing agents during ITI has been gaining support. This review presents a rationale and current data supporting the use of prophylactic bypassing agents as effective and safe therapies to reduce the incidence of joint bleeding due to inhibitors and improve quality of life in patients with HA undergoing ITI.

Radionuclide synovectomy/synoviorthesis (RS) in patients with bleeding disorders: A review of patient and procedure demographics and functional outcomes in the ATHNdataset.

INTRODUCTION: Radionuclide synovectomy/synoviorthesis (RS) to manage proliferative synovitis in persons with bleeding disorders has been utilized for decades; however, aggregate US results are limited. AIM: To determine the prevalence of RS utilization, patient and procedure related demographics and functional outcomes in United States haemophilia treatment centres (HTCs). The ATHNdataset includes US patients with bleeding disorders who have authorized the sharing of their demographic and clinical information for research. METHODS: We performed a multi-institutional, observational cohort study utilizing this dataset through 2010. Cases treated with RS procedure were compared to controls within the dataset. Standard template for data collection included patient and procedure related demographics as well as functional outcomes including range of motion (ROM) of the affected joint. Normative age- and sex-matched control ROM was obtained from published data. RESULTS: In the ATHNdataset there were 19 539 control-patients and 196 case-patients treated with RS. Patients with severe haemophilia were more likely to have had RS compared to those with mild/moderate haemophilia, although the proportion of RS performed was similar between severe HA and HB. Inhibitory antibodies, HIV and hepatitis C infection were significantly more common in cases. There were 362 RS procedures captured with 94 cases having >1 RS procedures. CONCLUSIONS: Right-sided joint procedures were more prevalent than left-sided procedures. Overall, case-patients had worse joint ROM compared to control-patients and published normative values. Geographically, there was regional variation in RS utilization, as the Southeast region had the largest percent of case-patients.

Blood-feeding patterns of native mosquitoes and insights into their potential role as pathogen vectors in the Thames estuary region of the United Kingdom.

BACKGROUND: The range of vertebrate hosts on which species of mosquito blood-feed is an important parameter for identifying potential vectors and in assessing the risk of incursion and establishment of vector-borne pathogens. In the United Kingdom, studies of mosquito host range have collected relatively few specimens and used techniques that could only broadly identify host species. This study conducted intensive collection and analysis of mosquitoes from a grazing marsh environment in southeast England. This site provides extensive wetland habitat for resident and migratory birds and has abundant human nuisance biting mosquitoes. The aim was to identify the blood-feeding patterns of mosquito species present at the site which could contribute to the transmission of pathogens. METHODS: Twice-weekly collections of mosquitoes were made from Elmley Nature Reserve, Kent, between June and October 2014. Mosquitoes were collected using resting boxes, by aspiration from man-made structures and using a Mosquito Magnet Pro baited with 1-octen-3-ol. Blood-fed specimens were classified according to the degree of blood meal digestion using the Sella scale and vertebrate origin determined using sequencing of a fragment of the mitochondrial cytochrome C oxidase subunit I gene. Mosquitoes that were morphologically cryptic were identified to species level using multiplex PCR and sequencing methods. RESULTS: A total of 20,666 mosquitoes of 11 species were collected, and 2,159 (10.4%) were blood-fed (Sella scale II-VI); of these 1,341 blood-fed specimens were selected for blood meal analysis. Vertebrate origin was successfully identified in 964 specimens (72%). Collections of blood-fed individuals were dominated by Anopheles maculipennis complex (73.5%), Culiseta annulata (21.2%) and Culex pipiens form pipiens (10.4%). Nineteen vertebrate hosts comprising five mammals and 14 birds were identified as hosts for mosquitoes, including two migratory bird species. Feeding on birds by Culex modestus and Anopheles atroparvus populations in England was demonstrated. CONCLUSIONS: This study expands the vertebrate host range of mosquitoes in the Thames estuary region of the UK. Feeding on both resident and migratory bird species by potential arbovirus vectors including Cx. pipiens f. pipiens and Cx. modestus indicates the potential for enzootic transmission of an introduced arbovirus between migratory and local bird species by native mosquito species.

Animal-to-Human Dose Translation of Obiltoxaximab for Treatment of Inhalational Anthrax Under the US FDA Animal Rule.

Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax under the US Food and Drug Administration's (FDA) Animal Rule. The human dose was selected and justified by comparing observed obiltoxaximab exposures in healthy and infected New Zealand White rabbits and cynomolgus macaques to observed exposures in healthy humans, to simulated exposures in healthy and infected humans, and to serum PA levels in infected animals. In humans, at 16 mg/kg intravenous, obiltoxaximab AUC was >2 times that in animals, while maximum serum concentrations were comparable to those in animals and were maintained in excess of the concentration required for PA neutralization in infected animals for 2-3 weeks. Obiltoxaximab 16 mg/kg in humans provided exposure beyond that of 16 mg/kg in animals, ensuring a sufficient duration of PA neutralization to allow for adaptive immunity development. Our approach to dose translation may be applicable to other agents being developed under the Animal Rule.

Morphometric discrimination of two sympatric sibling species in the Palaearctic region, Culicoides obsoletus Meigen and C. scoticus Downes & Kettle (Diptera: Ceratopogonidae), vectors of bluetongue and Schmallenberg viruses.

BACKGROUND: Some Palaearctic biting midge species (subgenus Avaritia) have been implicated as vectors of bluetongue virus in northern Europe. Separation of two species (C. obsoletus and C. scoticus) is considered difficult morphologically and, often, these female specimens are grouped in entomological studies. However, species-specific identification is desirable to understand their life history characteristics, assess their roles in disease transmission or measure their abundance during arboviral outbreaks. This study aims to investigate whether morphometric identification techniques can be applied to female C. obsoletus and C. scoticus individuals trapped at different geographical regions and time periods during the vector season. METHODS: C. obsoletus and C. scoticus were collected using light-suction traps from the UK, France and Spain, with two geographical locations sampled per country. A total of 759 C. obsoletus/C. scoticus individuals were identified using a molecular assay based on the cytochrome c oxidase subunit I gene. Fifteen morphometric measurements were taken from the head, wings and abdomen of slide-mounted specimens, and ratios calculated between these measurements. Multivariate analyses explored whether a combination of morphometric variables could lead to accurate species identification. Finally, Culicoides spp. collected in France at the start, middle and end of the adult vector season were compared, to determine whether seasonal variation exists in any of the morphometric measurements. RESULTS: The principal component analyses revealed that abdominal characteristics: length and width of the smaller and larger spermathecae, and the length of the chitinous plates and width between them, are the most reliable morphometric characteristics to differentiate between the species. Seasonal variation in the size of each species was observed for head and wing measurements, but not abdominal measurements. Geographical variation in the size of Culicoides spp. was also observed and is likely to be related to temperature at the trapping sites, with smaller individuals trapped at more southern latitudes. CONCLUSIONS: Our results suggest that female C. obsoletus and C. scoticus individuals can be separated under a stereomicroscope using abdominal measurements. Although we show the length and width of the spermathecae can be used to differentiate between the species, this can be time-consuming, so we recommend undertaking this using standardized subsampling of catches.

Female veterans' preferences for counseling related to intimate partner violence: Informing patient-centered interventions.

OBJECTIVE: Female veterans are at high risk for intimate partner violence (IPV). A critical issue in the provision of health care to women who experience IPV is the delivery of effective brief counseling interventions that address women's unique needs. We aimed to identify female veterans' priorities and preferences for healthcare-based IPV counseling. METHOD: A 2014 Web-based survey was administered to a national sample of US female veterans. Among 411 respondents (75% participation rate), 55% (n=226) reported IPV during their lifetime. These women identified priorities for the content focus of IPV-related counseling and preferences for the delivery of these services. RESULTS: Women prioritized counseling that focuses on physical safety and emotional health, with learning about community resources being a relatively lower priority. Participants preferred counseling to focus specifically on enhancing coping skills and managing mental health symptoms. In addition, women want counseling to be individualized and preferred the option to meet with a counselor immediately following disclosure. Affordable services and attention to privacy concerns were of paramount importance in the context of IPV-related counseling. CONCLUSION: These findings can inform patient-centered brief counseling interventions for women who experience IPV, which may ultimately reduce health disparities and violence among this population.

Evidence for marine origin and microbial-viral habitability of sub-zero hypersaline aqueous inclusions within permafrost near Barrow, Alaska.

Cryopegs are sub-surface hypersaline brines at sub-zero temperatures within permafrost; their global extent and distribution are unknown. The permafrost barrier to surface and groundwater advection maintains these brines as semi-isolated systems over geological time. A cryopeg 7 m below ground near Barrow, Alaska, was sampled for geochemical and microbiological analysis. Sub-surface brines (in situtemperature of -6 °C, salinity of 115 ppt), and an associated sediment-infused ice wedge (melt salinity of 0.04 ppt) were sampled using sterile technique. Major ionic concentrations in the brine corresponded more closely to other (Siberian) cryopegs than to Standard seawater or the ice wedge. Ionic ratios and stable isotope analysis of water conformed to a marine or brackish origin with subsequent Rayleigh fractionation. The brine contained ∼1000× more bacteria than surrounding ice, relatively high viral numbers suggestive of infection and reproduction, and an unusually high ratio of particulate to dissolved extracellular polysaccharide substances. A viral metagenome indicated a high frequency of temperate viruses and limited viral diversity compared to surface environments, with closest similarity to low water activity environments. Interpretations of the results underscore the isolation of these underexplored microbial ecosystems from past and present oceans.

Exposure to childhood trauma is associated with altered n-back activation and performance in healthy adults: implications for a commonly used working memory task.

Previous research suggests that a history of early life stress (ELS) impacts working memory (WM) in adulthood. Despite the widespread use of WM paradigms, few studies have evaluated whether ELS exposure, in the absence of psychiatric illness, also impacts WM-associated brain activity in ways that might improve sensitivity to these ELS effects or provide insights into the mechanisms of these effects. This study evaluated whether ELS affects WM behavioral performance and task-associated activity by acquiring 3T functional images from 27 medication-free healthy adults (14 with ELS) during an N-back WM task that included 0- and 2-back components. Whole brain voxel-wise analysis was performed to evaluate WM activation, followed by region of interest analyses to evaluate relationships between activation and clinical variables. ELS was associated with poorer accuracy during the 2-back (79% ± 19 vs. 92% ± 9, p = 0.049); accuracy and response time otherwise did not differ between groups. During the 0-back, ELS participants demonstrated increased activation in the superior temporal gyrus/insula, left inferior parietal lobule (IPL) (both corrected p < 0.001), and middle temporal and parahippocampal gyrus (MTG/PHG)(corrected p < 0.010). During the 2-back, ELS was associated with greater activation in the IPL, MTG/PHG and inferior frontal gyrus (corrected p < 0.001), with a trend towards precuneus activation (p = 0.080). These findings support previous research showing that ELS is associated with impaired neurobehavioral performance and changes in brain activation, suggesting recruitment of additional cognitive resources during WM in ELS. Based on these findings, ELS screening in future WM imaging studies appears warranted.

Wearing a Wetsuit Alters Upper Extremity Motion during Simulated Surfboard Paddling.

Surfers often wear wetsuits while paddling in the ocean. This neoprene covering may be beneficial to upper extremity movement by helping to improve proprioceptive acuity, or it may be detrimental by providing increased resistance. The purpose of this study was to evaluate the effects of wearing a wetsuit on muscle activation, upper extremity motion, heart rate, and oxygen consumption during simulated surfboard paddling in the laboratory. Twelve male, recreational surfers performed two paddling trials at a constant workload on a swim bench ergometer both with and without a wetsuit. Kinematic data and EMG were acquired from the right arm via motion capture, and oxygen consumption and heart rate were recorded with a metabolic cart and heart rate monitor. Wearing a wetsuit had no significant effect on oxygen consumption or heart rate. A significant increase in EMG activation was observed for the middle deltoid but not for any of the other shoulder muscle evaluated. Finally, approximate entropy and estimates of the maximum Lyapunov exponent increased significantly for vertical trajectory of the right wrist (i.e. stroke height) when a wetsuit was worn. These results suggest that a 2mm wetsuit has little effect on the energy cost of paddling at lower workloads but does affect arm motion. These changes may be the result of enhanced proprioceptive acuity due to mechanical compression from the wetsuit.