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This document corrects two errors in Eur. Phys. J. C77 (2017) no. 8, 56: the incorrect referencing of Fig. 1 labels in three paragraphs in the results section and a missing acknowledgements section.

A microfluidic system has been designed that integrates both imaged capillary isoelectric focusing (iCIEF) separations and downstream MS detection into a single assay. Along with the construction of novel instrumentation and an innovative microfluidic chip, conversion to MS‐compatible separation reagents has also been established. Incorporation of 280 nm absorbance iCIEF‐MS analysis not only permits photometric quantitation of separated charge isoforms but also facilitates the direct monitoring of analyte focusing and mobilization in real‐time. The outcome of this effort is a device with the unique ability to allow for both the characterization and identification of protein charge and mass isoforms in under 15 min. Acquisition, quantitation, and identification of highly resolved intact mAb charge isoforms along with their critical N‐linked glycan pairs clearly demonstrate analytical utility of our innovative system. In total, 33 separate molecular features were characterized by the iCIEF‐MS system representing a dramatic increase in the ability to monitor multiple intact mAb critical quality attributes in a single comprehensive assay. Unlike previously reported CIEF‐MS results, relatively high ampholyte concentrations, of up to 4% v/v, were employed without impacting MS sensitivity, observed to be on the order of 1% composition.

Background: A near vision game has been developed for the autostereoscopic screen of the Nintendo 3DS console. Ease of use and time for testing by non–English-speaking patients was not known. Methods: Adult and pediatric patients in a remote Burma clinic were compared with US military staff with each performing conventional near acuity, Stereo Fly, and Ishihara color in addition to PDI Check game, so results could be correlated and timed. Results: Seventeen Burma adults (aged 19–58), 20 Burma children (aged 7–15), and 14 US military staff (aged 21–36) completed the testing. Conventional testing correlated with PDI Check for stereo (P

Zusammenfassung. Im Allgemeinen wird in der Dermatologie unter einem Rundherd eine oft erythematöse, runde oder ovale Macula verstanden. Diese ist meist solitär, wird aber auch für multiple Rundherde bzw. Exantheme benutzt. Manchmal handelt es sich bei einem Rundherd auch um eine Plaque, also eine erhabene, grössere Fläche. Im vorliegenden Artikel wurden pigmentierte oder hypopigmentierte Maculae sowie knotige Tumore nicht eingeschlossen. Der isolierte Rundherd stellt, mehr noch wie multiple Rundherde, oft eine diagnostische Herausforderung dar und verlangt Kenntnisse der Klinik, Anamnese und Diagnostik.

Asiatic black bear Ursus thibetanus and sun bear Helarctos malayanus populations are declining throughout South-east Asia as a result of habitat loss and human disturbance. Knowledge of the distribution and status of each species is limited and largely anecdotal. Range maps are coarse, compiled by expert opinion, and presence or absence is unknown over large portions of South-east Asia. These two species co-occur in Lao People's Democratic Republic and may be faring better there than in neighbouring countries. During 2010–2013 we searched for bear sign along 99 transects within eight study sites throughout Lao. To explore countrywide relative abundance and habitat suitability, we modelled bear sign as a log-linear function of biological and anthropogenic predictors that were associated with habitat assemblages and human disturbance. Bears favored higher elevations and rugged terrain in areas less accessible to humans, and were most abundant in the north and east of Lao. Suitable habitats were rare in the southern lowland plains where bear abundance was relatively low. Our model predicted that Nam Et–Phou Louey National Protected Area had the largest areas of suitable bear habitat, followed by the Nakai-Nam Teun and Nam Ha National Protected Areas. Using transects to survey for bear sign, we created a replicable geographical information system based assessment tool for bears in Lao that can be used to identify conservation opportunities and monitor changes in bear distribution over time.

Background: Placing a spinal stimulator for the purpose of restoring paralysed function is a novel procedure; however, paralysis predisposes people to infection. Preventing surgical site infections is critical to benefit this population. Objective: The objective of this study was to review the root cause analysis of postoperative wound infections by a hospital epidemiology team following implantation of epidural spinal cord neurostimulators in patients with chronic spinal cord injury. Methods: A team was assembled to review the case of every individual who had been enrolled to receive a neurostimulator at the facility. A root cause analysis was performed evaluating five categories: the patient; equipment; facility/environment; procedure; and personnel. Findings: The root cause analysis included 11 patients. Two patients became infected. Three others dehisced their wound without becoming infected. All patients were given preoperative antibiotics on time. A mean of 17 personnel were in the operating room during surgery. Vancomycin powder was used in the patients who either dehisced their wound or became infected. Conclusions: The root cause analysis provides guidance for other institutions performing the same novel procedure. This analysis did not reveal a direct association, but did generate several areas for improvement including increasing pre-surgical screening, cleaning transient equipment (e.g., computer screens), limiting traffic in the operating room, using new sterile instruments for each stage of the procedure, not reopening the back incision, not applying vancomycin powder, and using an antimicrobial envelope for the stimulator.

The Gravity Recovery and Climate Experiment Follow-On mission was conceived to continue the successful legacy of the recently decommissioned Gravity Recovery and Climate Experiment mission and, at ...

Significance: A Nintendo® 3DS™ game can reliably test monocular near acuity, stereopsis and color without the need for occlusion patches or goggles. Purpose: We developed dynamic, forced-multiple choice games to measure monocular near acuity, color vision and stereopsis on the autostereoscopic barrier screen of the Nintendo 3DS gaming system. Methods: In an institutional review board-approved study, pediatric and adult patients and normal subjects performed routine patched near visual acuity, Ishahara's color test and Stereo Fly tests. Then each subject performed a two-phase orientation and testing game, "PDI Check", on a Nintendo 3DS. Results: Forty-five patients aged 5-60 years completed the routine and Nintendo near tests, resulting in positive, consistent, discriminatory correlation functions. From ROC curves, referral criteria were determined to separate poor from fair-to-normal monocular acuity with 98% sensitivity and 100% specificity, stereoacuity with 80% sensitivity and 97% specificity, and color with 83% sensitivity and 100% specificity. Conclusion: The Nintendo 3DS game PDI Check can provide consistent near vision testing via a dynamic, randomized method that does not require goggles for stereo, and does not require patching to assure monocular testing.

Despite conservation efforts, large mammals such as tigers (Panthera tigris) and their main prey, gaur (Bos gaurus), banteng (Bos javanicus), and sambar (Rusa unicolor), are highly threatened and declining across their entire range. The only large viable source population of tigers in mainland Southeast Asia occurs in Thailand's Western Forest Complex (WEFCOM), an approximately 19,000 km2 landscape of 17 contiguous protected areas.We used an occupancy modeling framework, which accounts for imperfect detection, to identify the factors that affect tiger distribution at the approximate scale of a female tiger's home range, 64 km2, and site use at a scale of 1‐km2. At the larger scale, we estimated the proportion of sites at WEFCOM that were occupied by tigers; at the finer scale, we identified the key variables that influence site‐use and developed a predictive distribution map. At both scales, we examined key anthropogenic and ecological factors that help explain tiger distribution and habitat use, including probabilities of gaur, banteng, and sambar occurrence from a companion study.Occupancy estimated at the 64‐km2 scale was primarily influenced by the combined presence of all three large prey species, and 37% or 5,858 km2 of the landscape was predicted to be occupied by tigers. In contrast, site use estimated at the scale of 1 km2 was most strongly influenced by the presence of sambar.By modeling occupancy while accounting for imperfect probability of detection, we established reliable benchmark data on the distribution of tigers in WEFCOM. This study also identified factors that limit tiger distributions; which managers can then target to expand tiger distribution and guide recovery elsewhere in Southeast Asia.

BackgroundThe impact of coronavirus disease 2019 extends far beyond the immediate burden on healthcare systems caused by hospitalisation of patients with the disease itself.ObjectiveTo investigate the impact of the coronavirus disease 2019 pandemic on the referral rate of patients to the suspected head and neck cancer two-week-wait clinic.MethodsA multicentre retrospective study was performed investigating data collected for all patients attending the suspected head and neck cancer two-week-wait clinic in ENT departments in the West Midlands.ResultsA total of 509 fast-track referrals were received from February to April in 2019, compared to 399 referrals in 2020. April 2020 saw a 62.4 per cent reduction in referral rate compared to April 2019.ConclusionThe coronavirus disease 2019 pandemic has resulted in changes to health-seeking behaviours, and healthcare provision and delivery. Urgent policy interventions may be required to compensate for the hidden impact that the coronavirus disease 2019 pandemic has had on those with cancer.

The management of sustainable harvest of animal populations is of great ecological and conservation importance. Development of formal quantitative tools to estimate and mitigate the impacts of harvest on animal populations has positively impacted conservation efforts. The vast majority of existing harvest models, however, do not simultaneously estimate ecological and harvest impacts on demographic parameters and population trends. Given that the impacts of ecological drivers are often equal to or greater than the effects of harvest, and can covary with harvest, this disconnect has the potential to lead to flawed inference. In this study, we used Bayesian hierarchical models and a 43-year capture-mark-recovery dataset from 404,241 female mallards Anas platyrhynchos released in the North American midcontinent to estimate mallard demographic parameters. Furthermore, we model the dynamics of waterfowl hunters and habitat, and the direct and indirect effects of anthropogenic and ecological processes on mallard demographic parameters. We demonstrate that density dependence, habitat conditions and harvest can simultaneously impact demographic parameters of female mallards, and discuss implications for existing and future harvest management models. Our results demonstrate the importance of controlling for multicollinearity among demographic drivers in harvest management models, and provide evidence for multiple mechanisms that lead to partial compensation of mallard harvest. We provide a novel model structure to assess these relationships that may allow for improved inference and prediction in future iterations of harvest management models across taxa.

PURPOSE: To determine whether smartphone photographs of children’s eyelids are reliable for diagnosing the presence of chalazia. METHODS: In this prospective cross-sectional study, 60 participants, 7 months to 16.5 years of age, at four sites were enrolled; all participants had a chalazion measuring at least 2 mm on at least one eyelid based on an in-person clinical examination by a pediatric eye care professional. Smartphone photographs taken by the parent during the office visit were uploaded to the study website. A masked reader assessed each photograph for the presence or absence of chalazia; results were compared with the gold standard clinical examination results. Sensitivity and specificity for the presence of chalazion by eyelid were calculated. RESULTS: Photographs were available for 240 eyelids; 85 had at least one chalazion and 155 were without a chalazion based on clinical examination. The masked reader correctly classified 68 of 85 eyelids with at least one chalazion and 151 of 155 eyelids without chalazia for a sensitivity of 80% (95% CI, 72%–86%) and a specificity of 97% (95% CI, 94%–99%). Sensitivity improved to 89% for chalazia 5 mm or larger and 94% when superficially located within the eyelid. CONCLUSIONS: Parental smartphone photographs appear to be useful in assessing chalazia in children as an alternative to in-office follow-up examinations. These photographs may be a valuable outcome measure in future clinical trials of chalazia treatment, especially when assessing larger lesions.

As instrument-based pediatric vision screening technology has evolved, the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) has developed uniform guidelines (2003, updated 2013) to inform the development of devices that can detect specified target levels of amblyopia risk factors (ARFs) and visually significant refractive error. Clinical experience with the established guidelines has revealed an apparent high level of over-referral for non-amblyopic, symmetric astigmatism, prompting the current revision.The revised guidelines reflect the expert consensus of the AAPOS Vision Screening and Research Committees.For studies of automated screening devices, AAPOS in 2021 recommends that the gold-standard confirmatory comprehensive examination failure levels include anisometropia1.25 D and hyperopia4.0 D. Astigmatism3.0 D in any meridian and myopia -3 D should be detected in children48 months, whereas astigmatism1.75 D and myopia-2 D should be detected after 48 months. Any media opacity1 mm and manifest strabismus of8Examination failure criteria have been simplified and the threshold for symmetric astigmatism raised compared to the 2013 guidelines, whereas the threshold for amblyogenic anisometropia has been decreased. After age 4 years, lower magnitudes of symmetric astigmatism and myopia are also targeted despite a low risk of amblyopia, because they can influence school performance and may warrant consideration of myopia prevention therapy.

Purpose: The lack of consistent data formatting for visual acuity in electronic medical records has led to inefficient data extraction and analysis. Methods: Prior acuity efforts were reviewed and analyzed relative to alpha-designated visual acuity. Prominent electronic medical record formatting was reviewed. Results: A table was generated facilitating the assignment of digital values to alpha acuities for metric and United States designation including centered steady maintained for infants and counting fingers, hand motions, light perception, and no light perception for patients with low vision. Discussion: Consistent and usable visual acuity data should lead to better research and eventually improve physician burn-out. [ J Pediatr Ophthalmol Strabismus . 2021;58(2):132–135.]

PURPOSE: The appropriate number of systematic biopsy cores to retrieve during magnetic resonance imaging (MRI)-targeted prostate biopsy is not well defined. We aimed to demonstrate a biopsy sampling approach that reduces required core count while maintaining diagnostic performance. MATERIALS AND METHODS: We collected data from a cohort of 971 men who underwent MRI-ultrasound fusion targeted biopsy for suspected prostate cancer. A regional targeted biopsy (RTB) was evaluated retrospectively; only cores within 2 cm of the margin of a radiologist-defined region of interest were considered part of the RTB. We compared detection rates for clinically significant prostate cancer (csPCa) and cancer upgrading rate on final whole mount pathology after prostatectomy between RTB, combined, MRI-targeted, and systematic biopsy. RESULTS: A total of 16,459 total cores from 971 men were included in the study data sets, of which 1,535 (9%) contained csPCa. The csPCa detection rates for systematic, MRI-targeted, combined, and RTB were 27.0% (262/971), 38.3% (372/971), 44.8% (435/971), and 44.0% (427/971), respectively. Combined biopsy detected significantly more csPCa than systematic and MRI-targeted biopsy (p

Complex dietary carbohydrate structures including β(1–4) galacto-oligosaccharides (GOS) are resistant to digestion in the upper gastrointestinal (GI) tract and arrive intact to the colon where they benefit the host by selectively stimulating microbial growth. Studies have reported the beneficial impact of GOS (alone or in combination with other prebiotics) by serving as metabolic substrates for modulating the assembly of the infant gut microbiome while reducing GI infections. N-Acetyl-D-lactosamine (LacNAc, Galβ1,4GlcNAc) is found in breast milk as a free disaccharide. This compound is also found as a component of human milk oligosaccharides (HMOs), which have repeating and variably branched lactose and/or LacNAc units, often attached to sialic acid and fucose monosaccharides. Human glycosyl-hydrolases do not degrade most HMOs, indicating that these structures have evolved as natural prebiotics to drive the proper assembly of the infant healthy gut microbiota. Here, we sought to develop a novel enzymatic method for generating LacNAc-enriched GOS, which we refer to as humanized GOS (hGOS). We showed that the membrane-bound β-hexosyl transferase (rBHT) from Hamamotoa (Sporobolomyces) singularis was able to generate GOS and hGOS from lactose and N-Acetyl-glucosamine (GlcNAc). The enzyme catalyzed the regio-selective, repeated addition of galactose from lactose to GlcNAc forming the β-galactosyl linkage at the 4-position of the GlcNAc and at the 1-position of D-galactose generating, in addition to GOS, LacNAc, and Galactosyl-LacNAc trisaccharides which were produced by two sequential transgalactosylations. Humanized GOS is chemically distinct from HMOs, and its effects in vivo have yet to be determined. Thus, we evaluated its safety and demonstrated the prebiotic's ability to modulate the gut microbiome in 6-week-old C57BL/6J mice. Longitudinal analysis of gut microbiome composition of stool samples collected from mice fed a diet containing hGOS for 5 weeks showed a transient reduction in alpha diversity. Differences in microbiome community composition mostly within the Firmicutes phylum were observed between hGOS and GOS, compared to control-fed animals. In sum, our study demonstrated the biological synthesis of hGOS, and signaled its safety and ability to modulate the gut microbiome in vivo, promoting the growth of beneficial microorganisms, including Bifidobacterium and Akkermansia.

Recent developments in machine learning algorithms have enabled models to exhibit impressive performance in healthcare tasks using electronic health record (EHR) data. However, the heterogeneous nature and sparsity of EHR data remains challenging. In this work, we present a model that utilizes heterogeneous data and addresses sparsity by representing diagnoses, procedures, and medication codes with temporal Hierarchical Clinical Embeddings combined with Topic modeling (HCET) on clinical notes. HCET aggregates various categories of EHR data and learns inherent structure based on hospital visits for an individual patient. We demonstrate the potential of the approach in the task of predicting depression at various time points prior to a clinical diagnosis. We found that HCET outperformed all baseline methods with a highest improvement of 0.07 in precision-recall area under the curve (PRAUC). Furthermore, applying attention weights across EHR data modalities significantly improved the performance as well as the model's interpretability by revealing the relative weight for each data modality. Our results demonstrate the model's ability to utilize heterogeneous EHR information to predict depression, which may have future implications for screening and early detection.

Histopathological images provide rich information for disease diagnosis. Large numbers of histopathological images have been digitized into high resolution whole slide images, opening opportunities in developing computational image analysis tools to reduce pathologists' workload and potentially improve inter- and intra- observer agreement. Most previous work on whole slide image analysis has focused on classification or segmentation of small pre-selected regions-of-interest, which requires fine-grained annotation and is non-trivial to extend for large-scale whole slide analysis. In this paper, we proposed a multi-resolution multiple instance learning model that leverages saliency maps to detect suspicious regions for fine-grained grade prediction. Instead of relying on expensive region- or pixel-level annotations, our model can be trained end-to-end with only slide-level labels. The model is developed on a large-scale prostate biopsy dataset containing 20,229 slides from 830 patients. The model achieved 92.7% accuracy, 81.8% Cohen's Kappa for benign, low grade (i.e. Grade group 1) and high grade (i.e. Grade group >= 2) prediction, an area under the receiver operating characteristic curve (AUROC) of 98.2% and an average precision (AP) of 97.4% for differentiating malignant and benign slides. The model obtained an AUROC of 99.4% and an AP of 99.8% for cancer detection on an external dataset., 9 pages, 6 figures

Introduction The virtual learning environment has become increasingly important due to physical distance requirements put in place during the COVID-19 pandemic. The transition to a virtual format has been challenging for case-based teaching sessions, which involve substantial audience participation. We developed a faculty development workshop aimed at teaching health professions educators how to use various interactive virtual tools within videoconferencing platforms to facilitate virtual case-based sessions. Methods Two 90-minute workshops were piloted as a faculty development initiative. The facilitators demonstrated interactive teaching tools that could be used within virtual case-based sessions. Then, participants discussed how to incorporate these tools into case-based teaching sessions of different class sizes in small-group breakout sessions. Participants completed an online survey following each workshop to evaluate the sessions. Results A total of 18 and 26 subjects participated in the first and second workshops, respectively. Survey response rates were 100% (n = 18) and 65% (n = 17) for the first and second workshops, respectively. Both groups provided overall high ratings and reported that the workshop was clear, organized, and relevant. Participants were more familiar and comfortable with the use of various interactive tools for online teaching. Discussion Distance online teaching will be increasingly required for an undetermined time. Faculty development efforts are crucial to facilitate effective interactive teaching sessions that engage learners and maximize learning. This virtual teaching workshop is a simple and straightforward way to introduce a more interactive format to virtual case-based teaching in the health professions.

Background The oculocardiac reflex (OCR) is a sudden vagal bradycardia that can be elicited by traction on an extraocular muscle. Bradycardia is highly variable from case to case necessitating a large sample size to observe small to moderate impact on OCR. While the surgeon’s tissue manipulation has immediate impact on OCR and individual patients may have some proclivity to OCR, we sought to characterize the impact on OCR by the anesthesiologist. Methods From 1992 to 2019, during routine, community outpatient general anesthetic strabismus surgery, oculocardiac reflex was prospectively observed utilizing a uniform 10-second, 200 gram square wave tension on each extraocular muscle. Anesthetic parameters were recorded and analyzed with double-cohort design and non-parametric statistics and correlations. We define %OCR as the maximally tension-altered heart rate and a percent of stable pre-tension heart rate. Results The median (IQR) confidence intervals OCR for 2527 initial cases was 89% (67% to 97%) without anticholinergic, and 99% (95% to 100%) in 165 patients with anticholinergic. OCR was 81% (62% to 96%) in 1034 with opioids and to 75% (60% to 95%) in 59 with dexmedetomidine and in 189 with IV dexamethasone to 72% (56% to 92%) There was a significant (p, Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/KX3gZ_OguLA

Background Community photoscreening for amblyopia had successfully been adopted by many communities, however many clinics curtailed screening as a result of the COVID-19 pandemic. We modified three conventional devices and tested them for outdoor, drive-by socially distanced photoscreening and refraction. Methods External frames that provide luminance control and focus distance were fashioned for plusoptiX S12 (Nuremberg, Germany), Adaptica 2WIN in Kaleidos case (Padova, Italy) and the Rebion blinq (Boston, USA). Children were screened by each device and then Retinomax (Righton, Japan) before AAPOS guideline validation. Results Eighty-eight children average age 8±7 years had precise refraction and alignment from which 69% AAPOS 2003 risk factors were determined. The sensitivity/specificity/inconclusive rate for plusoptiX was 85%/96%/16%, for 2WIN 79%/89%/5% and for blinq 43%/74%/8%. Blinq improved to 54%/70% when screening for amblyopia ± strabismus. Bland Altman analysis of spherical equivalent showed plusoptiX and 2WIN with less over-minus than Retinomax and J0 and J45 vectors highly reliable for astigmatism determination. Conclusion The infrared photorefractors in modified cases reliably screened amblyopia risk factors and refraction. The birefringent scanner provided drive-by results but less reliably with wire-frame opaque case than without the case in a dimly lit room. Modified drive-by photoscreeners could help reduce amblyopia and provide socially distanced refraction during an extended pandemic., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/CtgrnzKOvzY

Objective To characterize the decision-making process and illness experience of women with pelvic organ prolapse (POP) using large-scale social media analysis. Methods Digital ethnographic analysis of online posts identified through data mining was performed. Grounded theory methodology was applied to 200 posts via traditional hand coding. To supplement our qualitative approach, we applied a Latent Dirichlet Allocation probabilistic topic modeling process to review the entire data set of identified posts to ensure thematic saturation. Results There were 3451 posts by 2088 unique users from 117 websites worldwide that were identified via social media data mining. We found that the anonymity of online forums allowed for information and support exchange among women with POP. Our analysis revealed that the exchange of online information aids in the decision-making process and, in some instances, appears to be the primary source of information. There was confusion about the anatomical and surgical complexities of prolapse. Our study also identified misconceptions, perceived risk factors, prevention methods, and management recommendations that were discussed online. Conclusions This large-scale online community-based analysis demonstrated the utility of social media to better understand women's experiences with POP. Thematic findings highlighted essential concerns and challenges involved in the surgical decision-making process and the understating of the anatomical complexity of sector defects, specifically to cystocele, rectocele, State specific defects.

Camera traps are widely used to collect information on the distribution and abundance of multiple species simultaneously. However, we still lack important guidance for designing camera-trap surveys to monitor multiple species, and the consequences of species-specific responses to survey design strategies are often overlooked. Using camera-trap data collected on ten medium-to-large North-American carnivores in northern Minnesota, USA, between 2016 and 2018 (23 337 active trap-days), we evaluated: 1) two different survey-design frameworks (random- versus road-based), 2) two different lure types (salmon oil versus fatty acid scent oil), 3) two different placement strategies (completely random versus randomly-selected sites with feature-based placement), 4) survey timing (spring versus fall) and 5) temporal trends in daily encounter probabilities. Using generalized linear mixed models, we found evidence of differential responses to all of these design strategies. For 9 out of 10 species, we found strong responses to survey design frameworks: red foxes Vulpes vulpes, coyotes Canis latrans, bobcats, Lynx rufus, striped skunks Mephitis mephitis, wolves C. lupus and gray foxes Urocyon cinereoargenteus, had estimated encounter frequencies that were 9- to 106-fold higher at unlured sites along secondary roads; black bears Ursus americanus, martens Martes americana and fishers Pekania pennanti had estimated encounter frequencies that were 15- to > 3600-fold higher at lured, randomly selected sites. For six species, salmon oil provided 2- to 4-fold more encounters than fatty acid scent oil, but feature-basedplacement only improved detections of fishers. Daily encounter probabilities differed between spring and fall for all species, and usually decreased slightly within each sampling period Our study confirms that even similar-sized or closely-related species respond differently to survey-design choices. To maximize encounter frequencies, we recommend that multi-species camera-trap studies use a mix of survey-design strategies and include these design features during statistical analysis.

PURPOSE OF REVIEW: The purpose of this review is to address the relevant issues surrounding older adults with community-acquired pneumonia (CAP) today. RECENT FINDINGS: Approximately 1 million people >65 years have CAP in the US per year, which is more than previously reported (or realized). Older adults are vulnerable to the increasing prevalence of viral CAP, as the SARS-CoV-2 pandemic emphasizes, but pneumococcus is still the most common pathogen to cause CAP. Racial disparities continue to need to be addressed in order to improve early and late outcomes of older adults with CAP. SUMMARY: The epidemiology of CAP, specifically for older adults is changing. More recent pathogen incidence studies have included culture, as well as newer microbiological methods to determine etiology. Current disparities among disadvantaged populations, including African-Americans, result in more comorbidities which predisposes to more severe CAP. However, outcomes in the hospital between races tend to be similar, and outcomes between age groups tends to be worse for older compared to younger adults. Finally, the cost of CAP is significant compared to diabetes mellitus, myocardial infarction and stroke.

Purpose Developing large-scale datasets with research-quality annotations is challenging due to the high cost of refining clinically generated markup into high precision annotations. We evaluated the direct use of a large dataset with only clinically generated annotations in development of high-performance segmentation models for small research-quality challenge datasets. Materials and methods We used a large retrospective dataset from our institution comprised of 1,620 clinically generated segmentations, and two challenge datasets (PROMISE12: 50 patients, ProstateX-2: 99 patients). We trained a 3D U-Net convolutional neural network (CNN) segmentation model using our entire dataset, and used that model as a template to train models on the challenge datasets. We also trained versions of the template model using ablated proportions of our dataset, and evaluated the relative benefit of those templates for the final models. Finally, we trained a version of the template model using an out-of-domain brain cancer dataset, and evaluated the relevant benefit of that template for the final models. We used five-fold cross-validation (CV) for all training and evaluation across our entire dataset. Results Our model achieves state-of-the-art performance on our large dataset (mean overall Dice 0.916, average Hausdorff distance 0.135 across CV folds). Using this model as a pre-trained template for refining on two external datasets significantly enhanced performance (30% and 49% enhancement in Dice scores respectively). Mean overall Dice and mean average Hausdorff distance were 0.912 and 0.15 for the ProstateX-2 dataset, and 0.852 and 0.581 for the PROMISE12 dataset. Using even small quantities of data to train the template enhanced performance, with significant improvements using 5% or more of the data. Conclusion We trained a state-of-the-art model using unrefined clinical prostate annotations and found that its use as a template model significantly improved performance in other prostate segmentation tasks, even when trained with only 5% of the original dataset.

Learning under deep neural network models has shown interesting abilities to generate semi-structured sequences. Such generated fragments can appear to be remarkably like real data, yet applications of these generative techniques are generally lacking. This is partly due to the inability of recurrent neural network sequences to be semantically connected amongst long related fragments. One way to increase the semantics of these fragments is to combine features learned from topic modeling with those of recurrent neural networks. This combination ensures a higher correlation between generated sequences, much like real data. In this paper we investigate existing approaches to adding topics into the recurrent neural network. We then develop a novel approach called Topic-RNN, which represents the state-of-the-art technique of integrating topics into the RNN. Our results show this method outperforms existing approaches substantially. Additionally, we show that in such cases where topic information is available, Topic-RNN surpasses word level RNNs for the task of word prediction.

In this study, we propose the Ductal Instance-Oriented Pipeline (DIOP) that contains a duct-level instance segmentation model, a tissue-level semantic segmentation model, and three-levels of features for diagnostic classification. Based on recent advancements in instance segmentation and the Mask R-CNN model, our duct-level segmenter tries to identify each ductal individual inside a microscopic image; then, it extracts tissue-level information from the identified ductal instances. Leveraging three levels of information obtained from these ductal instances and also the histopathology image, the proposed DIOP outperforms previous approaches (both feature-based and CNN-based) in all diagnostic tasks; for the four-way classification task, the DIOP achieves comparable performance to general pathologists in this unique dataset. The proposed DIOP only takes a few seconds to run in the inference time, which could be used interactively on most modern computers. More clinical explorations are needed to study the robustness and generalizability of this system in the future., Comment: ICPR 2020. Submitted July 15th, 2020

Background Prebiotic galacto-oligosaccharides (GOS) have an extensively demonstrated beneficial impact on intestinal health. In this study, we determined the impact of GOS diets on hallmarks of gut aging: microbiome dysbiosis, inflammation, and intestinal barrier defects (“leaky gut”). We also evaluated if short-term GOS feeding influenced how the aging gut responded to antibiotic challenges in a mouse model of Clostridioides difficile infection. Finally, we assessed if colonic organoids could reproduce the GOS responder—non-responder phenotypes observed in vivo. Results Old animals had a distinct microbiome characterized by increased ratios of non-saccharolytic versus saccharolytic bacteria and, correspondingly, a lower abundance of β-galactosidases compared to young animals. GOS reduced the overall diversity, increased the abundance of specific saccharolytic bacteria (species of Bacteroides and Lactobacillus), increased the abundance of β-galactosidases in young and old animals, and increased the non-saccharolytic organisms; however, a robust, homogeneous bifidogenic effect was not observed. GOS reduced age-associated increased intestinal permeability and increased MUC2 expression and mucus thickness in old mice. Clyndamicin reduced the abundance Bifidobacterium while increasing Akkermansia, Clostridium, Coprococcus, Bacillus, Bacteroides, and Ruminococcus in old mice. The antibiotics were more impactful than GOS on modulating serum markers of inflammation. Higher serum levels of IL-17 and IL-6 were observed in control and GOS diets in the antibiotic groups, and within those groups, levels of IL-6 were higher in the GOS groups, regardless of age, and higher in the old compared to young animals in the control diet groups. RTqPCR revealed significantly increased gene expression of TNFα in distal colon tissue of old mice, which was decreased by the GOS diet. Colon transcriptomics analysis of mice fed GOS showed increased expression of genes involved in small-molecule metabolic processes and specifically the respirasome in old animals, which could indicate an increased oxidative metabolism and energetic efficiency. In young mice, GOS induced the expression of binding-related genes. The galectin gene Lgals1, a β-galactosyl-binding lectin that bridges molecules by their sugar moieties and is an important modulator of the immune response, and the PI3K-Akt and ECM-receptor interaction pathways were also induced in young mice. Stools from mice exhibiting variable bifidogenic response to GOS injected into colon organoids in the presence of prebiotics reproduced the response and non-response phenotypes observed in vivo suggesting that the composition and functionality of the microbiota are the main contributors to the phenotype. Conclusions Dietary GOS modulated homeostasis of the aging gut by promoting changes in microbiome composition and host gene expression, which was translated into decreased intestinal permeability and increased mucus production. Age was a determining factor on how prebiotics impacted the microbiome and expression of intestinal epithelial cells, especially apparent from the induction of galectin-1 in young but not old mice.

Highlights • Patients who were asymptomatic may transmit SARS-CoV-2. • Surveillance screening may decrease nosocomial transmission of SARS-CoV-2. • Common populations of asymptomatic patients were trauma and obstetrics., Background The proportion of positive patients admitted to acute-care hospitals for reasons other than coronavirus disease-19 (COVID-19) is unknown. These patients potentially put other patients and healthcare workers at risk of infection. Objective The objective of this study was to define the proportion of asymptomatic patients admitted with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Secondary objectives were to define the positivity rate, reasons for admission, and the geographic distribution in the region. Methods Universal surveillance testing for SARS-CoV-2 was performed on patients admitted to this hospital over a 12-week period from April 9, 2020 to July 1, 2020. Positive patients were categorized as either symptomatic or asymptomatic as defined by the 11 criteria per the Centers for Disease Control and Prevention. The positivity rate, proportion with and without symptoms, reasons for admission, and geographic distribution in the region were recorded. Results The positivity rate ranged from 0.8% to 6.2%. The proportion of asymptomatic patients with SARS-CoV-2 was 37%. Asymptomatic patients primarily presented to the hospital because of either trauma or labor. Some clusters in the region were identified of both symptomatic and asymptomatic patients. Conclusions The proportion of asymptomatic patients admitted with SARS-CoV-2 was significant. Identifying and isolating asymptomatic patients likely prevented exposure and development of hospital-acquired COVID-19 cases among healthcare workers and other patients, supporting the universal surveillance of all admitted patients.

The Dirichlet and hierarchical Dirichlet processes are two important techniques for nonparametric Bayesian learning. These learning techniques allow unsupervised learning without specifying traditionally used input parameters. In topic modeling, this can be applied to discovering topics without specifying the number beforehand. Existing methods, such as those applied to topic modeling, usually take on a complex sampling calculation for inference. These techniques for inference of the Dirichlet and hierarchal Dirichlet processes are often based on Markov processes that can deviate from parametric topic modeling. This deviation may not be the best approach in the context of nonparametric topic modeling. Additionally, since they often rely on approximations they can negatively affect the predictive power of such models. In this paper we introduce a new interpretation of nonparametric Bayesian learning called the biased coin flip process—contrived for use in the context of Bayesian topic modeling. We prove mathematically the equivalence of the biased coin flip process to the Dirichlet process with an additional parameter representing the number of trials. A major benefit of the biased coin flip process is the similarity of the inference calculation to that of previous established parametric topic models—which we hope will lead to a more widespread adoption of hierarchical Dirichlet process based topic modeling. Additionally, as we show empirically the biased coin flip process leads to a nonparametric topic model with improved predictive performance.