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Aims: This prospective study reports longitudinal, within-patient, patient-reported outcome measures (PROMs) over a 15-year period following cemented single radius total knee arthroplasty (TKA). Secondary aims included reporting PROMs trajectory, 15-year implant survival, and patient attrition from follow-up. Methods: From 2006 to 2007, 462 consecutive cemented cruciate-retaining Triathlon TKAs were implanted in 426 patients (mean age 69 years (21 to 89); 290 (62.7%) female). PROMs (12-item Short Form Survey (SF-12), Oxford Knee Score (OKS), and satisfaction) were assessed preoperatively and at one, five, ten, and 15 years. Kaplan-Meier survival and univariate analysis were performed. Results: At 15 years, 28 patients were lost to follow-up (6.1%) and 221 patients (51.9%) had died, with the mean age of the remaining cohort reducing by four years. PROMs response rates among surviving patients were: one-year 63%; five-year 72%; ten-year 94%; and 15-year 59%. OKS and SF-12 scores changed significantly over 15 years (p < 0.001). The mean improvement in OKS was 18.8 (95% confidence (CI) 16.7 to 19.0) at one year. OKS peaked at five years (median 43 years) declining thereafter (p < 0.001), though at 15 years it remained 17.5 better than preoperatively. Age and sex did not alter this trajectory. A quarter of patients experienced a clinically significant decline (≥ 7) in OKS from five to ten years and from ten to 15 years. The SF-12 physical component score displayed a similar trajectory, peaking at one year (p < 0.001). Patient satisfaction was 88% at one, five, and ten years, and 94% at 15 years. In all, 15-year Kaplan-Meier survival was 97.6% (95% CI 96.0% to 99.2%) for any revision, and 98.9% (95% CI 97.9% to 99.9%) for aseptic revision. Conclusion: Improvements in PROMs were significant and maintained following single radius TKA, with OKS peaking at five years, and generic physical health peaking at one year. Patient satisfaction remained high at 15 years, at which point 2.4% had been revised. Cite this article: Bone Jt Open 2023;4(10):808–816.

The IMbrave150 trial established atezolizumab with bevacizumab (A+B) as standard care for hepatocellular carcinoma (HCC), recommending an esophagogastroduodenoscopy (EGD) within 6 months of treatment initiation to prevent bleeding from esophagogastric varices. The necessity of mandatory EGD for all patients remains unclear. We retrospectively analyzed 112 HCC patients treated with A+B at five Canadian cancer centers from 1 July 2020 to 31 August 2022. A+B was the first-line therapy for 90% of patients, with median overall survival at 20.3 months and progression-free survival at 9.6 months. There was no survival difference between patients with bleeding and those without. Before A+B, 71% (n = 79) of patients underwent an EGD within 6 months, revealing varices in 41% (n = 32) and requiring intervention in 19% (n = 15). The overall bleeding rate was 15% (n = 17), with GI-specific bleeding occurring in 5% (n = 17). In the EGD group, GI-specific bleeding was 6% (n = 5) while in the non-EGD group, it was 3% (n = 1). Non-GI bleeding was observed in 10% (n = 11) of patients. Outcomes for HCC patients treated with A+B in Canada were comparable to IMbrave150. There was no increase in GI bleeding in patients without pre-treatment EGD, possibly supporting a selective EGD approach.

Plasmids are mobile genetic elements known to carry secondary metabolic genes that affect the fitness and survival of microbes in the environment. Well-studied cases of plasmid-encoded secondary metabolic genes in marine habitats include toxin/antitoxin and antibiotic biosynthesis/resistance genes. Here, we examine metagenome-assembled genomes (MAGs) from the permanently-stratified water column of the Cariaco Basin for integrated plasmids that encode biosynthetic gene clusters of secondary metabolites (smBGCs). We identify 16 plasmid-borne smBGCs in MAGs associated primarily with Planctomycetota and Pseudomonadota that encode terpene-synthesizing genes, and genes for production of ribosomal and non-ribosomal peptides. These identified genes encode for secondary metabolites that are mainly antimicrobial agents, and hence, their uptake via plasmids may increase the competitive advantage of those host taxa that acquire them. The ecological and evolutionary significance of smBGCs carried by prokaryotes in oxygen-depleted water columns is yet to be fully elucidated.

Abstract Background Perioperative infection and inflammation prophylaxis after ocular surgery has evolved over the years along with improvements in surgical equipment and a growing interest in alternatives to the standard topical eye drops. The purpose of this study is to evaluate the outcomes of a novel, modified-dropless protocol for 23-gauge (23-G), 25-gauge (25-G) and 27-gauge (27-G) micro-incision vitrectomy surgery (MIVS) that omits any intraocular injections of antibiotics or steroids. Methods This Institutional Review Board-approved, single-surgeon retrospective study reviewed MIVS post-surgical outcomes in patients who received a modified-dropless protocol from February 2020 to March 2021. A total of 158 charts were reviewed, of which 150 eyes met the eligibility criteria. After each case, patients were administered a 0.5 cc subconjunctival injection of a 1:1 Cefazolin (50 mg/cc):Dexamethasone (10 mg/cc) in the inferior fornix and 0.5 cc of posterior Sub-Tenon’s Kenalog (STK). No intravitreal injections were administered, and no pre- or postoperative antibiotic or steroid eye drops were prescribed. For patients allergic to penicillin, separate subconjunctival injections of 0.25 cc each of Vancomycin (10 mg/cc) and Dexamethasone (10 mg/cc) were administered. The primary safety parameter was postoperative cases of endophthalmitis. Secondary endpoints consisted of Best-Corrected Distance Visual Acuity (BCVA), intraocular pressure (IOP), and postoperative complications (retinal detachments, inflammation, need for additional surgery) within three months of surgery. Statistical analysis was performed using chi-square (χ²) tests for categorical values, and a Student’s t-test to compare continuous outcomes. Results The majority of surgeries (96%) were performed with the 27G MIVS platform. There were no cases of postoperative endophthalmitis. Mean logMAR BCVA improved from 0.71 (± 0.67) to 0.61 (± 0.60) post-operatively (p = 0.02). Excluding patients who had silicone oil tamponade, postoperative BCVA improved from 0.67 (± 0.66) to 0.54 (± 0.55) (p = 0.003). Mean IOP increased from 14.6 (± 3.8) to 15.3 (± 4.1) (p = 0.05). Ten patients required further medication therapy for an increase in IOP, one had inflammatory signs, and 14 required a second surgical intervention mostly due to recurrences of initial surgical indication. Conclusion A modified-dropless postoperative protocol involving subconjunctival and posterior sub-Tenon’s injections only may be a safe and convenient alternative to topical eye drops for patients undergoing MIVS, but additional and larger studies are needed.

Genome mining for biosynthetic gene clusters (BGCs) can be used for the discovery of new compounds of biotechnological interest. Here, the authors use metagenomics and metatranscriptomics to identify diverse BGCs in free-living and particle-associated microbial communities through the stratified water column of the Cariaco Basin, Venezuela.

We present the rest-frame ultraviolet−optical spectral properties of 65 broad absorption line (BAL) quasars from the Gemini Near Infrared Spectrograph−Distant Quasar Survey (GNIRS-DQS). These properties are compared with those of 195 non-BAL quasars from GNIRS-DQS in order to identify the drivers for the appearance of BALs in quasar spectra. In particular, we compare equivalent widths and velocity widths, as well as velocity offsets from systemic redshifts, of principal emission lines. In spite of the differences between their rest-frame ultraviolet spectra, we find that luminous BAL quasars are generally indistinguishable from their non-BAL counterparts in the rest-frame optical band at redshifts 1.55 ≲ z ≲ 3.50. We do not find any correlation between BAL trough properties and the H β -based supermassive black hole masses and normalized accretion rates in our sample. Considering the Sloan Digital Sky Survey quasar sample, which includes the GNIRS-DQS sample, we find that a monochromatic luminosity at rest-frame 2500 Å of ≳10 ^45 erg s ^−1 is a necessary condition for launching BAL outflows in quasars. We compare our findings with other BAL quasar samples and discuss the roles that accretion rate and orientation play in the appearance of BAL troughs in quasar spectra.

We present the optical–near-infrared spectral energy distributions (SED) and near-infrared variability properties of 30 low-redshift iron low-ionization Broad Absorption Line quasars (FeLoBALQs) and matched samples of LoBALQs and unabsorbed quasars. Significant correlations between the SED properties and accretion rate indicators found among the unabsorbed comparison sample objects suggest an intrinsic origin for SED differences. A range of reddening likely mutes these correlations among the FeLoBAL quasars. The rest-frame optical-band reddening is correlated with the location of the outflow, suggesting a link between the outflows and the presence of dust. We analyzed the WISE variability and provide a correction for photometry uncertainties in an appendix. We found an anticorrelation between the variability amplitude and inferred continuum emission region size, and we suggest that as the origin of the anticorrelation between variability amplitude and luminosity typically observed in quasars. We found that the LoBALQ Optical Emission-line and other parameters are more similar to those of the unabsorbed continuum sample objects than the FeLoBALQs. Thus, FeLoBAL quasars are a special population of objects. We interpret the results using an accretion-rate scenario for FeLoBAL quasars. The high-accretion-rate FeLoBAL quasars are radiating powerfully enough to drive a thick, high-velocity outflow. Quasars with intermediate accretion rates may have an outflow, but it is not sufficiently thick to include Fe ii absorption. Low-accretion-rate FeLoBAL outflows originate in absorption in a failing torus, no longer optically thick enough to reprocess radiation into the near-IR.

Abstract Background The COVID-19 pandemic and the consequent social distancing measures caused unprecedented disruption for medical and healthcare education. This study examined medical teachers’ experience with emergency remote teaching during the pandemic and their acceptance of online teaching after the pandemic. Methods In this sequential mixed methods study, online surveys were disseminated to teachers (n = 139) at two Asia–Pacific medical schools to evaluate their experience with emergency remote teaching during the pandemic. Subsequently, in-depth interviews were conducted with teachers from both institutions (n = 13). Each interviewee was classified into an adopter category based on Rogers’ Diffusion of Innovations Theory. Interview transcripts were analyzed thematically, and the descriptive themes were mapped to broader themes partly based on the Technology Acceptance Model and these included: (i) perceived usefulness of online teaching, (ii) perceived ease of delivering online teaching, (iii) experience with institutional support and (iv) acceptance of online teaching after the pandemic. Results Our participants described accounts of successes with their emergency remote teaching and difficulties they experienced. In general, most participants found it difficult to deliver clinical skills teaching remotely and manage large groups of students in synchronous online classes. With regards to institutional support, teachers with lower technological literacy required just-in-time technical support, while teachers who were innovative in their online teaching practices found that IT support alone could not fully address their needs. It was also found that teachers’ acceptance of online teaching after the pandemic was influenced by their belief about the usefulness of online teaching. Conclusions This study demonstrated that our participants managed to adapt to emergency remote teaching during this pandemic, and it also identified a myriad of drivers and blockers to online teaching adoption for medical teachers. It highlights the need for institutes to better support their teaching staff with diverse needs in their online teaching.

Purpose: Microcystic macular edema (MME), also known as retrograde maculopathy (RM), is associated with severe optic atrophy because of a range of causes. However, similar changes have also been described in primary retinal pathology and the pathogenesis of MME is debated. Design: A retrospective observational case series. Participants: Patients with nonarteritic ischemic optic neuropathy. Methods: A retrospective observational case series was performed at the University Hospital of Liège, Belgium. The medical records of patients who were referred to our Neuro-ophthalmology department with a diagnosis of nonarteritic anterior ischemic optic neuropathy (NA-AION), between 2014 and 2021, were reviewed. Main Outcome Measures: Ganglion cell complex thickness, acute and chronic inner nuclear change. Results: In a cohort of 34 patients (mean age: 60 ± 12.5 years; 65.6% men) with NA-AION, we identified a transient microcystic change in the inner nuclear layer (INL) associated with optic disc swelling in 19 eyes at presentation. This early change was associated with a transudate of intraretinal and subretinal fluid originating from the optic disc. Among patients who had shown this transient change 3 subsequently developed MME, which remained fixed during the period of observation (range, 12–34 months). No MME was observed in patients without an early INL transient change. Microcystic macular edema was observed in patients with severe ganglion cell complex thinning at 6 months: mean (± SD) loss in superior hemimacula (−28.2 ± 5.2 μm [−33.3%, range, −22.3 to −30.3 μm]) and in inferior hemimacula (−30.7 ± 5.6 μm [−31.0%, range, −24.3 to 34.8 μm]). Conclusions: Our study has revealed 2 causes of INL cystic change in the same patients experiencing NA-AION, 1 reversible and the other likely permanent. This finding highlights the distinction between genuine edema related to transudation of fluid (in this case secondary to ischemic optic disc swelling) and the phenomenon observed in RM that is related to the degree of retinal nerve fiber layer/ganglion cell complex thinning. Cystic change in the INL is associated with severe optic atrophy (MME). However, similar changes have been described in retinal pathology and the pathogenesis of MME is debated.

Fluoroscopy is increasingly used by gastroenterologists for endoscopic procedures such as endoscopic retrograde cholangiopancreatography. Unfortunately, fluoroscopy exposes patients and staff to ionizing radiation, which can cause DNA damage, cell death, genetic defects, and cancer. These adverse effects are more likely to occur with increased exposure time and higher radiation doses; therefore, all efforts to decrease exposure are helpful. In this study, we investigate the impact that updating the C-Arms in our endoscopy unit will have on radiation exposure by comparing ionizing radiation effects of the OEC 9900 Elite to the newer OEC Elite. After replicating the setup of a typical endoscopic retrograde cholangiopancreatography, ionizing radiation and energy were measured at the bedside and the head of the bed with each machine. At both positions, the newer OEC Elite C-Arm emitted less energy and ionizing radiation than the OEC 9900 Elite. Continuous imaging with OEC 9900 Elite emitted 0.12 mSv/h at the head of the bed and 0.49 mSv/h at the bedside, while the OEC Elite only emitted 0.04 mSv/h and 0.14 mSv/h, respectively. These values are measures of radiation-induced cancer risk, otherwise known as stochastic risk. The differences grow more significant when extrapolated to show radiation differences for an average procedure (approximately 8 minutes of fluoroscopy time) and the procedural volume for an entire year. In an effort to use as little radiation as possible, we see that we can significantly reduce radiation exposure to our staff by upgrading from an OEC 9900 Elite to and OEC Elite.

BackgroundEngaging students in interprofessional education for higher order thinking and collaborative problem-solving skills is challenging. This study reports the development of Virtual ER, a serious game played on a virtual platform, and how it can be an innovative way for delivering interprofessional education to medical and nursing undergraduates. ObjectiveWe report the development of a serious online game, Virtual ER, and evaluate its effect on teamwork enhancement and clinical competence. We also explore if Virtual ER can be an effective pedagogical tool to engage medical and nursing students with different learning styles. MethodsVirtual ER is a custom-made, learning outcome–driven, case-based web app. We developed a game performance scoring system with specific mechanisms to enhance serious gaming elements. Sixty-two students were recruited from our medical and nursing programs. They played the games in teams of 4 or 5, followed by an instructor-led debriefing for concept consolidation. Teamwork attitudes, as measured by the Human Factors Attitude Survey, were compared before and after the game. Learning style was measured with a modified Honey and Mumford learning style questionnaire. ResultsStudents were satisfied with Virtual ER (mean satisfaction score 5.44, SD 0.95, of a possible 7). Overall, Virtual ER enhanced teamwork attitude by 3.02 points (95% CI 1.15-4.88, P=.002). Students with higher scores as activists (estimate 9.09, 95% CI 5.17-13.02, P

Abstract Energy storage systems utilizing neutral pH aqueous electrolytes are increasing in importance, as they are inherently cheaper and safer when compared to their traditional lithium‐ion battery counterparts. However, no thorough study on binder characteristics in the aqueous environment has been reported. This work reports the performance and characterization of multiple binders: a polyacrylonitrile‐based binder (LA133), LA133+carboxymethyl cellulose (CMC), styrene‐butadiene rubber (SBR), SBR+CMC, polytetrafluoroethylene (PTFE), and PTFE+CMC as implemented with a LiMn2O4 cathode in a neutral pH aqueous electrolyte. Data presented include cyclic voltammetry (CV), resistivity, and scanning electron microscopy (SEM) results. PTFE+CMC is the overall superior binder, particular touting superior rate performance owing to the strength of PTFE coupled with electrolyte swelling ability of CMC. This work hopes to serve as a resource for rational design of sustainable battery chemistries.

Studying microbes from a single-cell perspective has become a major theme and interest within the field of aquatic microbiology. One emerging trend is the unfailing observation of heterogeneity in activity levels within microbial populations. Wherever researchers have looked, intra-population variability in biochemical composition, growth rates, and responses to varying environmental conditions has been evident and probably reflect coexisting genetically distinct strains of the same species. Such observations of heterogeneity require a shift away from bulk analytical approaches and development of new methods or adaptation of existing techniques, many of which were first pioneered in other, unrelated fields, e.g., material, physical, and biomedical sciences. Many co-opted approaches were initially optimized using model organisms. In a field with so few cultivable models, method development has been challenging but has also contributed tremendous insights, breakthroughs, and stimulated curiosity. In this perspective, we present a subset of methods that have been effectively applied to study aquatic microbes at the single-cell level. Opportunities and challenges for innovation are also discussed. We suggest future directions for aquatic microbiological research that will benefit from open access to sophisticated instruments and highly interdisciplinary collaborations.

Broad absorption line quasars are actively accreting supermassive black holes that have strong outflows characterized by broad absorption lines in their rest-UV spectra. Variability in these absorption lines occurs over months to years depending on the source. WPVS 007, a low-redshift, low-luminosity narrow-line Seyfert 1 (NLS1) shows strong variability over shorter timescales, providing a unique opportunity to study the driving mechanism behind this variability that may mimic longer-scale variability in much more massive quasars. We present the first variability study using the spectral synthesis code SimBAL , which provides velocity-resolved changes in physical conditions of the gas using constraints from multiple absorption lines. Overall, we find WPVS 007 to have a highly ionized outflow with a large mass-loss rate and kinetic luminosity. We determine the primary cause of the absorption-line variability in WPVS 007 to be a change in covering fraction of the continuum by the outflow. This study is the first SimBAL analysis where multiple epochs of observation were fit simultaneously, demonstrating the ability of SimBAL to use the time domain as an additional constraint in spectral models.

Development of the Rubin Observatory Legacy Survey of Space and Time (LSST) includes a series of Data Challenges (DCs) arranged by various LSST Scientific Collaborations that are taking place during the project's preoperational phase. The AGN Science Collaboration Data Challenge (AGNSC-DC) is a partial prototype of the expected LSST data on active galactic nuclei (AGNs), aimed at validating machine learning approaches for AGN selection and characterization in large surveys like LSST. The AGNSC-DC took place in 2021, focusing on accuracy, robustness, and scalability. The training and the blinded data sets were constructed to mimic the future LSST release catalogs using the data from the Sloan Digital Sky Survey Stripe 82 region and the XMM-Newton Large Scale Structure Survey region. Data features were divided into astrometry, photometry, color, morphology, redshift, and class label with the addition of variability features and images. We present the results of four submitted solutions to DCs using both classical and machine learning methods. We systematically test the performance of supervised models (support vector machine, random forest, extreme gradient boosting, artificial neural network, convolutional neural network) and unsupervised ones (deep embedding clustering) when applied to the problem of classifying/clustering sources as stars, galaxies, or AGNs. We obtained classification accuracy of 97.5% for supervised models and clustering accuracy of 96.0% for unsupervised ones and 95.0% with a classic approach for a blinded data set. We find that variability features significantly improve the accuracy of the trained models, and correlation analysis among different bands enables a fast and inexpensive first-order selection of quasar candidates.

The most reliable single-epoch supermassive black hole mass ( M _BH ) estimates in quasars are obtained by using the velocity widths of low-ionization emission lines, typically the H β λ 4861 line. Unfortunately, this line is redshifted out of the optical band at z ≈ 1, leaving M _BH estimates to rely on proxy rest-frame ultraviolet (UV) emission lines, such as C iv λ 1549 or Mg ii λ 2800, which contain intrinsic challenges when measuring, resulting in uncertain M _BH estimates. In this work, we aim at correcting M _BH estimates derived from the C iv and Mg ii emission lines based on estimates derived from the H β emission line. We find that employing the equivalent width of C iv in deriving M _BH estimates based on Mg ii and C iv provides values that are closest to those obtained from H β . We also provide prescriptions to estimate M _BH values when only C iv , only Mg ii , and both C iv and Mg ii are measurable. We find that utilizing both emission lines, where available, reduces the scatter of UV-based M _BH estimates by ∼15% when compared to previous studies. Lastly, we discuss the potential of our prescriptions to provide more accurate and precise estimates of M _BH given a much larger sample of quasars at 3.20 ≲ z ≲ 3.50, where both Mg ii and H β can be measured in the same near-infrared spectrum.

Quasars at z ≳ 1 most often have redshifts measured from rest-frame ultraviolet emission lines. One of the most common such lines, C iv λ 1549, shows blueshifts up to ≈5000 km s ^−1 and in rare cases even higher. This blueshifting results in highly uncertain redshifts when compared to redshift determinations from rest-frame optical emission lines, e.g., from the narrow [O iii ] λ 5007 feature. We present spectroscopic measurements for 260 sources at 1.55 ≲ z ≲ 3.50 having −28.0 ≲ M _i ≲ − 30.0 mag from the Gemini Near Infrared Spectrograph–Distant Quasar Survey (GNIRS-DQS) catalog, augmenting the previous iteration, which contained 226 of the 260 sources whose measurements are improved upon in this work. We obtain reliable systemic redshifts based on [O iii ] λ 5007 for a subset of 121 sources, which we use to calibrate prescriptions for correcting UV-based redshifts. These prescriptions are based on a regression analysis involving C iv full-width-at-half-maximum intensity and equivalent width, along with the UV continuum luminosity at a rest-frame wavelength of 1350 Å. Applying these corrections can improve the accuracy and the precision in the C iv -based redshift by up to ∼850 km s ^−1 and ∼150 km s ^−1 , respectively, which correspond to ∼8.5 and ∼1.5 Mpc in comoving distance at z = 2.5. Our prescriptions also improve the accuracy of the best available multifeature redshift determination algorithm by ∼100 km s ^−1 , indicating that the spectroscopic properties of the C iv emission line can provide robust redshift estimates for high-redshift quasars. We discuss the prospects of our prescriptions for cosmological and quasar studies utilizing upcoming large spectroscopic surveys.

Weak emission-line quasars (WLQs) are a subset of type 1 quasars that exhibit extremely weak Ly α + N v λ 1240 and/or C iv λ 1549 emission lines. We investigate the relationship between emission-line properties and accretion rate for a sample of 230 “ordinary” type 1 quasars and 18 WLQs at z < 0.5 and 1.5 < z < 3.5 that have rest-frame ultraviolet and optical spectral measurements. We apply a correction to the H β -based black hole mass ( M _BH ) estimates of these quasars using the strength of the optical Fe ii emission. We confirm previous findings that WLQs’ M _BH values are overestimated by up to an order of magnitude using the traditional broad-emission-line region size–luminosity relation. With this M _BH correction, we find a significant correlation between H β -based Eddington luminosity ratios and a combination of the rest-frame C iv equivalent width and C iv blueshift with respect to the systemic redshift. This correlation holds for both ordinary quasars and WLQs, which suggests that the two-dimensional C iv parameter space can serve as an indicator of accretion rate in all type 1 quasars across a wide range of spectral properties.

Abstract Background To evaluate visual and safety outcomes for 25-gauge (25G) and 27-gauge (27G) micro-incision vitrectomy platforms (MIVS) for the treatment of epiretinal membrane and full-thickness macular holes. Methods Retrospective analysis of all patients who underwent internal limiting membrane (ILM) peel surgery from January 2017 through December 2018. 207 cases met the eligibility criteria for inclusion. Primary endpoint was post-operative Best-Corrected Distance Visual Acuity (BCVA) at 6 months. Results For all patients combined, mean logMAR BCVA improved from 0.57 (± 0.40) to 0.37 (± 0.36) post-operatively (p

Oxygen-depleted water columns (ODWCs) host a diverse community of eukaryotic protists that change dramatically in composition over the oxic-anoxic gradient. In the permanently anoxic Cariaco Basin, peaks in eukaryotic diversity occurred in layers where dark microbial activity (chemoautotrophy and heterotrophy) were highest, suggesting a link between prokaryotic activity and trophic associations with protists. Using 18S rRNA gene sequencing, parasites and especially the obligate parasitic clade, Syndiniales, appear to be particularly abundant, suggesting parasitism is an important, but overlooked interaction in ODWC food webs. Syndiniales were also associated with certain prokaryotic groups that are often found in ODWCs, including Marinimicrobia and Marine Group II archaea, evocative of feedbacks between parasitic infection events, release of organic matter, and prokaryotic assimilative activity. In a network analysis that included all three domains of life, bacterial and archaeal taxa were putative bottleneck and hub species, while a large proportion of edges were connected to eukaryotic nodes. Inclusion of parasites resulted in a more complex network with longer path lengths between members. Together, these results suggest that protists, and especially protistan parasites, play an important role in maintaining microbial food web complexity, particularly in ODWCs, where protist diversity and microbial productivity are high, but energy resources are limited relative to euphotic waters.

Abstract Background The control of lymphatic filariasis (LF) caused by Wuchereria bancrofti in the Central African Region has been hampered by the presence of Loa loa due to severe adverse events that arise in the treatment with ivermectin. The immunochromatographic test (ICT) cards used for mapping LF demonstrated cross-reactivity with L. loa and posed the problem of delineating the LF map. To verify LF endemicity in forest areas of Cameroon where mass drug administration (MDA) has not been ongoing, we used the recently developed strategy that combined serology, microscopy and molecular techniques. Methods This study was carried out in 124 communities in 31 health districts (HDs) where L. loa is present. At least 125 persons per site were screened. Diurnal blood samples were investigated for circulating filarial antigen (CFA) by FTS and for L. loa microfilariae (mf) using TBF. FTS positive individuals were further subjected to night blood collection for detecting W. bancrofti. qPCR was used to detect DNA of the parasites. Results Overall, 14,446 individuals took part in this study, 233 participants tested positive with FTS in 29 HDs, with positivity rates ranging from 0.0 to 8.2%. No W. bancrofti mf was found in the night blood of any individuals but L. loa mf were found in both day and night blood of participants who were FTS positive. Also, qPCR revealed that no W. bancrofti but L.loa DNA was found with dry bloodspot. Positive FTS results were strongly associated with high L. loa mf load. Similarly, a strong positive association was observed between FTS positivity and L loa prevalence. Conclusions Using a combination of parasitological and molecular tools, we were unable to find evidence of W. bancrofti presence in the 31 HDs, but L. loa instead. Therefore, LF is not endemic and LF MDA is not required in these districts.

While visual assessment by a clinician is the standard of care for burn severity evaluations, new technologies at various stages of development are attempting to add objectivity to this practice by quantifying burn severity. Assessment accuracy generally improves after the burn injury has progressed, but early assessments that correctly identify superficial partial and deep partial burns have the potential to lead to more prompt treatments and shorter recovery times. To date, Spatial Frequency Domain Imaging (SFDI) has only been used in animal models of burns, but has shown the potential to categorize burns accurately at earlier time points. Here we examine the potential for SFDI to assess burn severity in clinical patients. We also utilize Laser Speckle Imaging (LSI), an FDA cleared non-invasive imaging technology that typically measures blood perfusion in order to evaluate burns in clinical patients. We present a case series of two patients, both with partial thickness burns of varying severity. Partial thickness burns are often difficult for clinicians to categorize based on visual appearance alone. SFDI and LSI were both performed on each patient at approximately 24 and 72 h after their respective burn incidents. Each technique was able to render spatially resolved information that enabled improved assessment accuracy for each burn. This represents the first publication of SFDI applied to clinical burn patients after being successfully utilized in animal models, and highlights the potential for SFDI as a feasible tool for the timely categorization of burn severity. Keywords: Burns, Clinical, Humans, Spatial Frequency Domain Imaging, Laser Speckle Imaging

Emiliania huxleyi is a cosmopolitan member of the marine phytoplankton. This species’ capacities for carbon sequestration and sulfur mobilization make it a key player in oceanic biogeochemical cycles that influence climate on a planetary scale. Seasonal E. huxleyi blooms are abruptly terminated by viral epidemics caused by a clade of large DNA viruses collectively known as coccolithoviruses (EhVs). EhVs thereby mediate a significant part of material and energy fluxes associated with E. huxleyi population dynamics. In this study, we use spontaneous Raman microspectroscopy to perform label-free and non-invasive measurements of the macromolecular composition of individual virions and E. huxleyi host cells. Our novel autofluorescence suppression protocol enabled spectroscopic visualization of evolving macromolecular redistributions in individual E. huxleyi cells at different stages of EhV infection. Material transfer from E. huxleyi hosts to single EhV-163 virions was confirmed by combining stable isotope probing (SIP) experiments with Raman microspectroscopy. Inheritance of the host cells’ 13C-enriched isotopic signature was quantified based on red shifts of Raman peaks characteristic of phenylalanine’s phenyl ring. Two-dimensional Raman mapping of EhV-infected E. huxleyi cells revealed that the compact region producing an intense Raman DNA signal (i.e., the nucleus) in healthy E. huxleyi cells becomes diffuse during the first hours of infection. Raman DNA emissions integrated throughout individual cells decreased during the infection cycle. Our observations are consistent with EhV-163 degrading the host’s nuclear DNA, scavenging released nucleotides for its own genome replication, and shedding newly-produced virions prior to host lysis via budding.

Over recent years, mounting pressure has been placed on countries to assess their role in the ivory trade, with a view to tackling the rapidly declining numbers of elephants, due to poaching. The United Kingdom has been identified as a large re-exporter of ivory. Despite much of this trade being reported as legal or antique ivory, such provision of ivory to meet demand is known to fuel illegal markets and provide trade routes for modern ivory sales. Aside from ivory species and age, further analysis to evaluate geographic provenance, can inform where an elephant had lived, and so identify a source region or population where poaching occurred. The purpose of this study was to determine the age and species of ivory objects surrendered or seized in the UK and assess their likely geographic provenance through comparison of results from mitochondrial DNA and stable isotope analysis to publicly accessible georeferenced African elephant databases. The results demonstrated that the objects tested from an airport seizure were modern and matched existing haplotypes allowing for regional geographic inferences (supported by both techniques) to be obtained for most of these objects. In contrast, antique and modern ivory was detected amongst the amnesty objects, and several new mtDNA haplotypes were identified. Regional geographic inferences were achieved for some but not all of the objects tested. Our findings show this combination of methods provides a wealth of information which, could provide insight into targeted elephant populations and assist in disrupting international wildlife trade networks.

Background: Lower urinary tract symptoms (LUTS) in men may indicate bladder outlet obstruction (BOO) or weakness, known as detrusor underactivity (DU). Severe bothersome LUTS are a common indication for surgery. The diagnostic tests may include urodynamics (UDS) to confirm whether BOO or DU is the cause, potentially reducing the number of people receiving (inappropriate) surgery. Objectives: The primary objective was to determine whether a care pathway including UDS is no worse for symptom outcome than one in which it is omitted, at 18 months after randomisation. Rates of surgery was the key secondary outcome. Design: This was a pragmatic, multicentre, two-arm (unblinded) randomised controlled trial, incorporating a health economic analysis and qualitative research. Setting: Urology departments of 26 NHS hospitals in England. Participants: Men (aged ≥ 18 years) seeking further treatment, potentially including surgery, for bothersome LUTS. Exclusion criteria were as follows: unable to pass urine without a catheter, having a relevant neurological disease, currently undergoing treatment for prostate or bladder cancer, previously had prostate surgery, not medically fit for surgery and/or unwilling to be randomised. Interventions: Men were randomised to a care pathway based on non-invasive routine tests (control) or routine care plus invasive UDS (intervention arm). Main outcome measures: The primary outcome was International Prostate Symptom Score (IPSS) at 18 months after randomisation and the key secondary outcome was rates of surgery. Additional secondary outcomes included adverse events (AEs), quality of life, urinary and sexual symptoms, UDS satisfaction, maximum urinary flow rate and cost-effectiveness. Results: A total of 820 men were randomised (UDS, 427; routine care, 393). Sixty-seven men withdrew before 18 months and 11 died (unrelated to trial procedures). UDS was non-inferior to routine care for IPSS 18 months after randomisation, with a confidence interval (CI) within the margin of 1 point (–0.33, 95% CI –1.47 to 0.80). A lower surgery rate in the UDS arm was not found (38% and 36% for UDS and routine care, respectively), with overall rates lower than expected. AEs were similar between the arms at 43–44%. There were more cases of acute urinary retention in the routine care arm. Patient-reported outcomes for LUTS improved in both arms and satisfaction with UDS was high in men who received it. UDS was more expensive than routine care. From a secondary care perspective, UDS cost an additional £216 over an 18-month time horizon. Quality-adjusted life-years (QALYs) were similar, with a QALY difference of 0.006 in favour of UDS over 18 months. It was established that UDS was acceptable to patients, and valued by both patients and clinicians for its perceived additional insight into the cause and probable best treatment of LUTS. Limitations: The trial met its predefined recruitment target, but surgery rates were lower than anticipated. Conclusions: Inclusion of UDS in the diagnostic tests results in a symptom outcome that is non-inferior to a routine care pathway, but does not affect surgical rates for treating BOO. Results do not support the routine use of UDS in men undergoing investigation of LUTS. Future work: Focus should be placed on indications for selective utilisation of UDS in individual cases and long-term outcomes of diagnosis and therapy. Trial registration: Current Controlled Trials ISRCTN56164274. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 42. See the NIHR Journals Library website for further project information.

The Eastern Tropical North Pacific (ETNP) is a large, persistent, and intensifying oxygen minimum zone (OMZ) that accounts for almost half of the total area of global OMZs. Within the OMZ core (∼350–700 m depth), dissolved oxygen is typically near or below the analytical detection limit of modern sensors (∼10 nM). Steep oxygen gradients above and below the OMZ core lead to vertical structuring of microbial communities that also vary between particle-associated (PA) and free-living (FL) size fractions. Here, we use 16S amplicon sequencing (iTags) to analyze the diversity and distribution of prokaryotic populations between FL and PA size fractions and among the range of ambient redox conditions. The hydrographic conditions at our study area were distinct from those previously reported in the ETNP and other OMZs, such as the ETSP. Trace oxygen concentrations (∼0.35 μM) were present throughout the OMZ core at our sampling location. Consequently, nitrite accumulations typically reported for OMZ cores were absent as were sequences for anammox bacteria (Brocadiales genus Candidatus Scalindua), which are commonly found across oxic-anoxic boundaries in other systems. However, ammonia-oxidizing bacteria (AOB) and archaea (AOA) distributions and maximal autotrophic carbon assimilation rates (1.4 μM C d–1) coincided with a pronounced ammonium concentration maximum near the top of the OMZ core. In addition, members of the genus Nitrospina, a dominant nitrite-oxidizing bacterial (NOB) clade were present suggesting that both ammonia and nitrite oxidation occur at trace oxygen concentrations. Analysis of similarity test (ANOSIM) and Non-metric Dimensional Scaling (nMDS) revealed that bacterial and archaeal phylogenetic representations were significantly different between size fractions. Based on ANOSIM and iTag profiles, composition of PA assemblages was less influenced by the prevailing depth-dependent biogeochemical regime than the FL fraction. Based on the presence of AOA, NOB and trace oxygen in the OMZ core we suggest that nitrification is an active process in the nitrogen cycle of this region of the ETNP OMZ.

SignificanceOver the past decade, machine learning (ML) algorithms have rapidly become much more widespread for numerous biomedical applications, including the diagnosis and categorization of disease and injury.AimHere, we seek to characterize the recent growth of ML techniques that use imaging data to classify burn wound severity and report on the accuracies of different approaches.ApproachTo this end, we present a comprehensive literature review of preclinical and clinical studies using ML techniques to classify the severity of burn wounds.ResultsThe majority of these reports used digital color photographs as input data to the classification algorithms, but recently there has been an increasing prevalence of the use of ML approaches using input data from more advanced optical imaging modalities (e.g., multispectral and hyperspectral imaging, optical coherence tomography), in addition to multimodal techniques. The classification accuracy of the different methods is reported; it typically ranges from ∼70% to 90% relative to the current gold standard of clinical judgment.ConclusionsThe field would benefit from systematic analysis of the effects of different input data modalities, training/testing sets, and ML classifiers on the reported accuracy. Despite this current limitation, ML-based algorithms show significant promise for assisting in objectively classifying burn wound severity.

Background: Posterior cortical atrophy (PCA), the visual variant of Alzheimer's disease, leads to high-level visual deficits such as alexia or agnosia. Visual field deficits have also been identified, but often inconsistently reported. Little is known about the pattern of visual field deficits or the underlying cortical changes leading to this visual loss. Methods: Multi-modal magnetic resonance imaging was used to investigate differences in gray matter volume, cortical thickness, white matter microstructure and functional activity in patients with PCA compared to age-matched controls. Additional analyses investigated hemispheric asymmetries in these metrics according to the visual field most affected by the disease. Results: Analysis of structural data indicated considerable loss of gray matter in the occipital and parietal cortices, lateralized to the hemisphere contralateral to the visual loss. This lateralized pattern of gray matter loss was also evident in the hippocampus and parahippocampal gyrus. Diffusion-weighted imaging showed considerable effects of PCA on white matter microstructure in the occipital cortex, and in the corpus callosum. The change in white matter was only lateralized in the occipital lobe, however, with greatest change in the optic radiation contralateral to the visual field deficit. Indeed, there was a significant correlation between the laterality of the optic radiation microstructure and visual field loss. Conclusions: Detailed brain imaging shows that the asymmetric visual field deficits in patients with PCA reflect the pattern of degeneration of both white and gray matter in the occipital lobe. Understanding the nature of both visual field deficits and the neurodegenerative brain changes in PCA may improve diagnosis and understanding of this disease.

Heroism has only recently become a topic of empirical investigation. Existing research suggests a connection between heroism and four well-documented dimensions of human social behavior: (1) the cost incurred by the actor; (2) the benefit provided to the recipient; (3) the perceived frequency (i.e., descriptive normativity); and (4) the perceived expectation to perform it (i.e., injunctive normativity). In a series of exploratory studies (total N = 408), we aim to shed light on how each of these constructs influence lay intuitions about the nature of heroism (i.e., what determines which acts people perceive to be heroic). In Study 1, subjects generated a list of acts they deemed to be heroic. In Study 2, subjects rated the heroicness of the acts from Study 1, revealing considerable variation in the level of heroism. Finally, subjects in Study 3 rated the cost to the actor, the benefit to the recipient(s), the descriptive normativity (i.e., frequency), and the injunctive normativity (i.e., obligatoriness) of ten acts, five of which received particularly high heroism scores in Study 2 (“exemplary” acts of heroism) and five of which received particularly low heroism scores in Study 2 (“ambiguous” acts of heroism). We find that more heroic acts are seen as rarer and more costly to actors—but, interestingly, not more beneficial to recipients or less obligatory. These findings help to illuminate what it means to be seen as a hero, and suggest clear future directions for both empirical and theoretical work.

Lesions of primary visual cortex or its primary inputs typically result in retinotopically localized scotomas. Here we present an individual with unexplained visual field loss and deficits in visual perception in the absence of structural damage to the early visual pathway or lesions in visual cortex. The subject, monocular from an early age, underwent repeated perimetry tests over 8 years demonstrating severe anopia of the lower hemifield, and a clockwise progression of the loss through her upper left visual field. Her visual impairment was evident in a number of standardized tests and psychophysics, especially in tasks assessing spatial integration using illusory contours. However, her intellectual ability was intact and her performance in some other tasks assessing color vision or object detection in scenes was normal. We employed functional magnetic resonance imaging (fMRI), electroretinography and visually evoked potentials. Surprisingly, in contrast to the participant’s severe anopia, we found no evidence of abnormal function of her early visual pathways. Specifically, we performed retinotopic mapping using population receptive field (pRF) analysis to map the functional organization of visual cortex in the anopic participant and three control participants on two occasions three and a half years apart. Despite the behavioral visual field loss, her retinotopic maps and pRF parameters in visual areas V1–V3 were qualitatively normal. Further behavioral experiments confirmed that this discrepancy was not trivially explained by the difference between stimuli used for retinotopic mapping and perimetry. Structural T1 scans were normal at both time points, and volumetric analysis of white and gray matter tissue on the segmented T1 volumes did not reveal any abnormalities or deterioration over time. Our findings suggest that normal functional organization of early visual cortex without evident structural damage to the early visual pathway as disclosed by the techniques employed in this study does not necessarily guarantee conscious perception across the visual field.

SignificanceStudying cerebral hemodynamics may provide diagnostic information on neurological conditions. Wide-field imaging techniques, such as laser speckle imaging (LSI) and optical intrinsic signal imaging, are commonly used to study cerebral hemodynamics. However, they often do not account appropriately for the optical properties of the brain that can vary among subjects and even during a single measurement. Here, we describe the combination of LSI and spatial-frequency domain imaging (SFDI) into a wide-field quantitative hemodynamic imaging (QHI) system that can correct the effects of optical properties on LSI measurements to achieve a quantitative measurement of cerebral blood flow (CBF).AimWe describe the design, fabrication, and testing of QHI.ApproachThe QHI hardware combines LSI and SFDI with spatial and temporal synchronization. We characterized system sensitivity, accuracy, and precision with tissue-mimicking phantoms. With SFDI optical property measurements, we describe a method derived from dynamic light scattering to obtain absolute CBF values from LSI and SFDI measurements. We illustrate the potential benefits of absolute CBF measurements in resting-state and dynamic experiments.ResultsQHI achieved a 50-Hz raw acquisition frame rate with a 10×10  mm field of view and flow sensitivity up to ∼4  mm/s. The extracted SFDI optical properties agreed well with a commercial system (R2≥0.98). The system showed high stability with low coefficients of variations over multiple sessions within the same day (

Ozonation followed by a polishing moving bed biofilm reactor (MBBR) was implemented in pilot and laboratory to remove the residual pharmaceuticals and toxicity from wastewater effluent, which was from a pilot hybrid system of MBBR and activated sludge, receiving municipal wastewater. The delivered ozone dosages achieving 90% pharmaceutical removal were determined both in pilot and laboratory experiments and they were normalised to dissolved organic carbon (DOC), illustrating our findings were comparable with previously published literature. During wastewater ozonation, the intensity of natural fluorescence was found to be greatly associated with the concentrations of the studied pharmaceuticals. In pilot experiments, toxicity, measured by Vibrio fischeri, increased after ozonation at delivered ozone dosages at 0.38–0.47 mg O3/mg DOC and was completely removed by the subsequent polishing MBBR. Laboratory experiments verified that the polishing MBBR was able to remove the toxicity produced by the ozonation.

A consistent set of measurement techniques must be applied to reliably and reproducibly evaluate the efficacy of treatments for cutaneous neurofibromas (cNFs) in people with neurofibromatosis type 1 (NF1). cNFs are neurocutaneous tumors that are the most common tumor in people with NF1 and represent an area of unmet clinical need. This review presents the available data regarding approaches in use or development to identify, measure, and track cNFs, including calipers, digital imaging, and high-frequency ultrasound sonography. We also describe emerging technologies such as spatial frequency domain imaging and the application of imaging modalities such as optical coherence tomography that may enable the detection of early cNFs and prevention of tumor-associated morbidity.

Posterior cortical atrophy (PCA) is a syndromic diagnosis. It is characterized by progressive impairment of higher (cortical) visual function with imaging evidence of degeneration affecting the occipital, parietal, and posterior temporal lobes bilaterally. Most cases will prove to have Alzheimer pathology. The aim of this review is to summarize the development of the concept of this disorder since it was first introduced. A critical discussion of the evolving diagnostic criteria is presented and the differential diagnosis with regard to the underlying pathology is reviewed. Emphasis is given to the visual dysfunction that defines the disorder, and the classical deficits, such as simultanagnosia and visual agnosia, as well as the more recently recognized visual field defects, are reviewed, along with the evidence on their neural correlates. The latest developments on the imaging of PCA are summarized, with special attention to its role on the differential diagnosis with related conditions.