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Purpose: Patient-report outcome measures (PROMs) have gained widespread support as a mechanism to improve healthcare quality. We aimed to map out key enablers and barriers influencing PROMs implementation strategies in routine clinical practice. Methods: An umbrella review was conducted to identify reviews exploring enablers and barriers related to the integration of PROMs in routine clinical practice from January 2000 to June 2023. Information on key enablers and barriers was extracted and summarised thematically according to the Theoretical Domains Framework. Results: 34 reviews met our criteria for inclusion. Identified reviews highlighted barriers such as limited PROMs awareness among clinicians and patients, perceived low value by clinicians and patients, PROMs that were too complex or difficult for patients to complete, poor usability of PROMs systems, delayed feedback of PROMs data, clinician concerns related to use of PROMs as a performance management tool, patient concerns regarding privacy and security, and resource constraints. Enablers encompassed phased implementation, professional training, stakeholder engagement prior to implementation, clear strategies and goals, 'change champions' to support PROMs implementation, systems to respond to issues raised by PROMs, and integration into patient pathways. No consensus favoured paper or electronic PROMs, yet offering both options to mitigate digital literacy bias and integrating PROMs into electronic health records emerged as important facilitators. Conclusions: The sustainable implementation of PROMs is a complex process that requires multicomponent organisational strategies covering training and guidance, necessary time and resources, roles and responsibilities, and consultation with patients and clinicians. [ABSTRACT FROM AUTHOR]

Regulatory frameworks for artificial intelligence (AI) are needed to mitigate risks while ensuring the ethical, secure, and effective implementation of AI technology in healthcare and population health. In this article, we present a synthesis of 141 binding policies applicable to AI in healthcare and population health in the EU and 10 European countries. The EU AI Act sets the overall regulatory framework for AI, while other legislations set social, health, and human rights standards, address the safety of technologies and the implementation of innovation, and ensure the protection and safe use of data. Regulation specifically pertaining to AI is still nascent and scarce, though a combination of data, technology, innovation, and health and human rights policy has already formed a baseline regulatory framework for AI in health. Future work should explore specific regulatory challenges, especially with respect to AI medical devices, data protection, and data enablement. [ABSTRACT FROM AUTHOR]

Robotics researchers have been focusing on developing autonomous and human-like intelligent robots that are able to plan, navigate, manipulate objects, and interact with humans in both static and dynamic environments. These capabilities, however, are usually developed for direct interactions with people in controlled environments, and evaluated primarily in terms of human safety. Consequently, human-robot interaction (HRI) in scenarios with no intervention of technical personnel is under-explored. However, in the future, robots will be deployed in unstructured and unsupervised environments where they will be expected to work unsupervised on tasks which require direct interaction with humans and may not necessarily be collaborative. Developing such robots requires comparing the effectiveness and efficiency of similar design approaches and techniques. Yet, issues regarding the reproducibility of results, comparing different approaches between research groups, and creating challenging milestones to measure performance and development over time make this difficult. Here we discuss the international robotics competition called RoboCup as a benchmark for the progress and open challenges in AI and robotics development. The long term goal of RoboCup is developing a robot soccer team that can win against the world’s best human soccer team by 2050. We selected RoboCup because it requires robots to be able to play with and against humans in unstructured environments, such as uneven fields and natural lighting conditions, and it challenges the known accepted dynamics in HRI. Considering the current state of robotics technology, RoboCup’s goal opens up several open research questions to be addressed by roboticists. In this paper, we (a) summarise the current challenges in robotics by using RoboCup development as an evaluation metric, (b) discuss the state-of-the-art approaches to these challenges and how they currently apply to RoboCup, and (c) present a path for future development in the given areas to meet RoboCup’s goal of having robots play soccer against and with humans by 2050. [ABSTRACT FROM AUTHOR]

The Think/No-Think (TNT) task has just celebrated 20 years since its inception, and its use has been growing as a tool to investigate the mechanisms underlying memory control and its neural underpinnings. Here, we present a theoretical and practical guide for designing, implementing, and running TNT studies. For this purpose, we provide a step-by-step description of the structure of the TNT task, methodological choices that can be made, parameters that can be chosen, instruments available, aspects to be aware of, systematic information about how to run a study and analyze the data. Importantly, we provide a TNT training package (as Supplementary Material), that is, a series of multimedia materials (e.g., tutorial videos, informative HTML pages, MATLAB code to run experiments, questionnaires, scoring sheets, etc.) to complement this method paper and facilitate a deeper understanding of the TNT task, its rationale, and how to set it up in practice. Given the recent discussion about the replication crisis in the behavioral sciences, we hope that this contribution will increase standardization, reliability, and replicability across laboratories. [ABSTRACT FROM AUTHOR]

It is well known that molecules confined very close to a surface arrange into molecular layers. Because solid-liquid interfaces are ubiquitous in the chemical, biological and physical sciences, it is crucial to develop methods to easily access molecular layers and exploit their distinct properties by producing molecular layered crystals. Here we report a method based on crystallization in ultra-thin puddles enabled by gas blowing, which allows to produce molecular layered crystals with thickness down to the monolayer onto a surface, making them directly accessible for characterization and further processing. By selecting four molecules with different types of polymorphs, we observed exclusive crystallization of polymorphs with Van der Waals interlayer interactions, which have not been observed with traditional confinement methods. In conclusion, the gas blowing approach unveils the opportunity to perform materials chemistry under confinement onto a surface, enabling the formation of distinct crystals with selected polymorphism. Molecules arranged in close proximity to a surface form molecular layers, exhibiting distinct properties. However, the creation of these layers is challenging. Here, the authors present a technique for generating molecular layers through crystallization induced by gas blowing onto a surface. [ABSTRACT FROM AUTHOR]

Background: High-need, high-cost Medicare patients can have difficulties accessing office-based primary care. Home-based primary care (HBPC) can reduce access barriers and allow a clinician to obtain valuable information not obtained during office visit, possibly leading to reductions in hospital use. Objective: To determine whether HBPC for high-need, high-cost patients reduces hospitalizations and Medicare inpatient expenditures. Design: We conducted a matched retrospective cohort study using a difference-in-differences analysis to examine patients 2 years before and 2 years after their first home visit (HBPC group). Participants: The study included high-need, high-cost fee-for-service Medicare patients without prior HBPC use, of which 55,303 were new HBPC recipients and 156,142 were matched comparison patients. Intervention: Receipt of at least two HBPC visits and, within 6 months of the index HBPC visit, a majority of a patient's primary care visits in the home. Main Measures: Total and potentially avoidable hospitalizations and Medicare inpatient expenditures. Key Results: HBPC reduced total hospitalization rates, but the marginal effects were not statistically significant: a reduction of 11 total hospitalizations per 1000 patients in the first year (− 0.6%, p = 0.19) and 14 in the second year (− 0.7%, p = 0.16). However, HBPC reduced potentially avoidable hospitalization rates in the second year. The estimated marginal effect was a reduction of 6 potentially avoidable hospitalizations per 1000 patients in the first year (− 1.6%, p = 0.16) and 11 in the second (− 3.1%, p = 0.01). The estimated effect of HBPC was a small decrease in inpatient expenditures of $24 per patient per month (− 1.1%, p = 0.10) in the first year and $0 (0.0%, p = 0.99) in the second. Conclusions: After high-need, high-cost patients started receiving HBPC, they did not experience fewer total hospitalizations or lower inpatient spending but may have had lower rates of potentially avoidable hospitalizations after 2 years. [ABSTRACT FROM AUTHOR]

The Sierra Nevada and Southern Cascades—California's snowy mountains—are primary freshwater sources and natural reservoirs for the states of California and Nevada. These mountains receive precipitation overwhelmingly from wintertime storms including atmospheric rivers (ARs), much of it falling as snow at the higher elevations. Using a seven-decade record of daily observed temperature and precipitation as well as a snow reanalysis and downscaled climate projections, we documented historical and future changes in snow accumulation and snowlines. In four key subregions of California's snowy mountains, we quantified the progressing contribution of ARs and non-AR storms to the evolving and projected snow accumulation and snowlines (elevation of the snow-to-rain transition), exploring their climatology, variability and trends. Historically, snow makes up roughly a third of the precipitation affecting California's mountains. While ARs make up only a quarter of all precipitating days and, due to their relative warmth, produce snowlines higher than do other storms, they contribute over 40% of the total seasonal snow. Under projected unabated warming, snow accumulation would decline to less than half of historical by the late twenty-first century, with the greatest snow loss at mid elevations (from 1500 to 3300 m by the mountain sub-regions) during fall and spring. Central and Southern Sierra Nevada peaks above 3400 m might see occasionally extreme snow accumulations in January–February resulting entirely from wetter ARs. AR-related snowlines are projected to increase by more than 700 m, compared to about 500 m for other storms. We discuss likely impacts of the changing climate for water resources as well as for winter recreation. [ABSTRACT FROM AUTHOR]

Qualifying critical reagents in ligand binding assays by parallel testing of current and candidate reagent lots is recommended by regulatory agencies and industry groups, but specific guidance on the format of reagent qualification experiments is limited. Equivalence testing is a statistically sound approach that is consistent with the objective of critical reagent qualification. We present power analysis for equivalence regions ranging from 1.25- to 1.5-fold multiples of the GM ratio (centered on 1) of current and candidate lots, over a range of assay variability from 5 to 30% coefficient of variation (CV). A 1.25-fold equivalence region can be tested using 6 to 12 plates per lot for assays with up to 15% CV but is not practical for more variable assays. For these assays, wider equivalence regions are justified so long as care is taken to avoid assay drift and the assay remains suitable for the intended use. The equivalence test method is illustrated using historical data from passing and failing reagent qualification experiments. Simulation analysis was performed to support the design of qualification experiments using 6, 12, or 18 plates per lot over a broad range of assay variability. A challenge in implementing the equivalence test approach is selecting an appropriate equivalence region. Equivalence regions providing 90% power using 12 plates/lot were consistent with 1.5σ bounds, which are recommended for equivalence testing of critical quality attributes of biosimilars. [ABSTRACT FROM AUTHOR]

Suppressing retrieval of unwanted memories can cause forgetting, an outcome often attributed to the recruitment of inhibitory control. This suppression-induced forgetting (SIF) generalizes to different cues used to test the suppressed content (cue-independence), a property taken as consistent with inhibition. But does cue-independent forgetting necessarily imply that a memory has been inhibited? Tomlinson et al. (Proc Natl Acad Sci 106:15588–15593, 2009) reported a surprising finding that pressing a button also led to cue-independent forgetting, which was taken as support for an alternative interference account. Here we investigated the role of inhibition in forgetting due to retrieval suppression and pressing buttons. We modified Tomlinson et al.'s procedure to examine an unusual feature they introduced that may have caused memory inhibition effects in their experiment: the omission of explicit task-cues. When tasks were uncued, we replicated the button-press forgetting effect; but when cued, pressing buttons caused no forgetting. Moreover, button-press forgetting partially reflects output-interference effects at test and not a lasting effect of interference. In contrast, SIF occurred regardless of these procedural changes. Collectively, these findings indicate that simply pressing a button does not induce forgetting, on its own, without confounding factors that introduce inhibition into the task and that inhibition likely underlies SIF. [ABSTRACT FROM AUTHOR]

Melioidosis is an endemic disease in numerous tropical regions. Additionally, the bacterium that causes melioidosis, Burkholderia pseudomallei, has potential to be used as a biological weapon. Therefore, development of effective and affordable medical countermeasures to serve regions affected by the disease and to have medical countermeasures available in the event of a bioterrorism attack remains critical. The current study evaluated the efficacy of eight distinct acute phase ceftazidime treatment regimens administered therapeutically in the murine model. At the conclusion of the treatment period, survival rates were significantly greater in several of the treated groups when compared to the control group. Pharmacokinetics of a single dose of ceftazidime were examined at 150 mg/kg, 300 mg/kg, and 600 mg/kg and were compared to an intravenous clinical dose administered at 2000 mg every eight hours. The clinical dose has an estimated 100% fT > 4*MIC which exceeded the highest murine dose of 300 mg/kg every six hours at 87.2% fT > 4*MIC. Based upon survival at the end of the treatment regimen and supplemented by pharmacokinetic modeling, a daily dose of 1200 mg/kg of ceftazidime, administered every 6 h at 300 mg/kg, provides protection in the acute phase of inhalation melioidosis in the murine model. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of cytomegalovirus (CMV) colitis in the setting of severe ulcerative colitis (UC) remains a clinical challenge. This study aimed to determine the utility of serum CMV polymerase chain reaction (PCR) as a non-invasive test for the diagnosis of CMV superinfection in patients hospitalized with UC. Methods: This retrospective study included consecutive admitted patients with UC who had serum testing for CMV completed as part of standard hospital procedure and CMV colitis diagnosed by expert pathologists. Results: Two hundred and six patients with UC were included; 13 patients (6%) had histologically confirmed CMV colitis. Eleven of 13 patients with CMV colitis (84%) and 3 of 193 (1.5%) patients without CMV colitis had a positive serum PCR test (p < 0.0001). ROC analysis showed that a CMV PCR level of 259 IU/mL had a sensitivity and specificity of 77% and 99%, respectively, for diagnosis of CMV colitis with an AUC of 0.9 (p < 0.0001). Serum CMV PCR level significantly correlated to the number of inclusion bodies on biopsy specimens with data available (n = 8) (r = 0.8, p = 0.02). CMV positivity did not predict the need for salvage therapy, admission or 1-year colectomy rates. Conclusion: Serum CMV PCR has an excellent negative predictive value and demonstrates a strong correlation with CMV positivity on histology. This work supports a rationale for serum CMV PCR testing on admission to assess the risk of CMV colitis in patients with severe UC. [ABSTRACT FROM AUTHOR]

This study provides extended seasonal predictions for the Upper Colorado River Basin (UCRB) precipitation in boreal spring using an artificial neural network (ANN) model and a stepwise linear regression model, respectively. Sea surface temperature (SST) predictors are developed taking advantage of the correlation between the precipitation and SST over three ocean basins. The extratropical North Pacific has a higher correlation with the UCRB spring precipitation than the tropical Pacific and North Atlantic. For the ANN model, the Pearson correlation coefficient between the observed and predicted precipitation exceeds 0.45 (p-value < 0.01) for a lead time of 12 months. The mean absolute percentage error (MAPE) is below 20% and the Heidke skill score (HSS) is above 50%. Such long-lead prediction skill is probably due to the UCRB soil moisture bridging the SST and precipitation. The stepwise linear regression model shows similar prediction skills to those of ANN. Both models show prediction skills superior to those of an autoregression model (correlation < 0.10) that represents the baseline prediction skill and those of three of the North American Multi-Model Ensemble (NMME) forecast models. The three NMME models exhibit different skills in predicting the precipitation, with the best skills of the correlation ~ 0.40, MAPE < 25%, and HSS > 40% for lead times less than 8 months. This study highlights the advantage of oceanic climate signals in extended seasonal predictions for the UCRB spring precipitation and supports the improvement of the UCRB streamflow prediction and related water resource decisions. [ABSTRACT FROM AUTHOR]

Remembering unpleasant events can trigger negative feelings. Fortunately, research indicates that unwanted retrieval can be suppressed to prevent memories from intruding into awareness, improving our mental state. The current scientific understanding of retrieval suppression, however, is based mostly on simpler memories, such as associations between words or pictures, which may not reflect how people control unpleasant memory intrusions in everyday life. Here, we investigated the neural and behavioural dynamics of suppressing personal and emotional autobiographical memories using a modified version of the Think/No-Think task. We asked participants to suppress memories of their own past immoral actions, which were hypothesised to be both highly intrusive and motivating to suppress. We report novel evidence from behavioural, ERP, and EEG oscillation measures that autobiographical memory retrieval can be suppressed and suggest that autobiographical suppression recruits similar neurocognitive mechanisms as suppression of simple laboratory associations. Suppression did fail sometimes, and EEG oscillations indicated that such memory intrusions occurred from lapses in sustained control. Importantly, however, participants improved at limiting intrusions with repeated practice. Furthermore, both behavioural and EEG evidence indicated that intentional suppression may be more difficult for memories of our morally wrong actions than memories of our morally right actions. The findings elucidate the neurocognitive correlates of autobiographical retrieval suppression and have implications for theories of morally motivated memory control. [ABSTRACT FROM AUTHOR]

Background: The independent healthcare sector in the UK collects PROMs for several surgical procedures, but implementation has been challenging. We aimed to understand the enablers and barriers to PROMs implementation in the independent healthcare sector in the UK. Method: Between January and May 2021, we remotely conducted semi-structured interviews with hospital consultants, hospital managers and other clinical staff using a topic guide developed from an implementation science framework called the Theoretical Domains Framework (TDF). Results: We interviewed 6 hospital consultants, 5 hospital managers, and 3 other clinical staff (1 nurse and 2 physiotherapists) across 8 hospitals. Common barriers included: the perception that PROMs are predominantly a reporting requirement rather than a quality improvement tool, absence of feedback mechanisms for PROMs data for clinicians, poor awareness of PROMs among healthcare professionals and the public, absence of direction or commitment from leadership, and limited support from hospital consultants. Common enablers included: regular feedback of PROMs data to clinicians, designating roles and responsibilities, formally embedding PROMs collection into patient pathways, and involvement of hospital consultants in developing strategies to improve PROMs uptake. Conclusion: To support PROMs implementation, independent hospitals need to develop long-term organisational strategies that involve sustained leadership commitment, goals or targets, training opportunities to staff, and regular feedback of PROMs data at clinical or governance meetings. The primary purpose of PROMs needs to be reframed to independent healthcare sector stakeholders as a quality improvement tool rather than a reporting requirement. [ABSTRACT FROM AUTHOR]

“The physics of representation” (Poldrack, 2020) aims to (1) define the word “representation” as used in the neurosciences, (2) argue that such representations as described in neuroscience are related to and usefully illuminated by the representations generated by modern neural networks, and (3) establish that these entities are “representations in good standing”. We suggest that Poldrack succeeds in (1), exposes some tensions between the broad use of the term in neuroscience and the narrower class of entities that he identifies in the end, and between the meaning of “representation” in neuroscience and in psychology in (2), and fails in (3). This results in some hard choices: give up on the broad scope of the term in neuroscience (and thereby potentially opening a gap between psychology and neuroscience) or continue to embrace the broad, psychologically inflected sense of the term, and deny the entities generated by neural nets (and the brain) are representations in the relevant sense. [ABSTRACT FROM AUTHOR]

Over the last two decades, inhibitory control has featured prominently in accounts of how humans and other organisms regulate their behaviour and thought. Previous work on how the brain stops actions and thoughts, however, has emphasised distinct prefrontal regions supporting these functions, suggesting domain-specific mechanisms. Here we show that stopping actions and thoughts recruits common regions in the right dorsolateral and ventrolateral prefrontal cortex to suppress diverse content, via dynamic targeting. Within each region, classifiers trained to distinguish action-stopping from action-execution also identify when people are suppressing their thoughts (and vice versa). Effective connectivity analysis reveals that both prefrontal regions contribute to action and thought stopping by targeting the motor cortex or the hippocampus, depending on the goal, to suppress their task-specific activity. These findings support the existence of a domain-general system that underlies inhibitory control and establish Dynamic Targeting as a mechanism enabling this ability. The authors use fMRI to show that the ability to stop unwanted actions and thoughts arises from a common stopping mechanism that flexibly inhibits activity in diverse, content-specific brain areas. [ABSTRACT FROM AUTHOR]

Suppression-induced forgetting (SIF) refers to a memory impairment resulting from repeated attempts to stop the retrieval of unwanted memory associates. SIF has become established in the literature through a growing number of reports built upon the Think/No-Think (TNT) paradigm. Not all individuals and not all reported experiments yield reliable forgetting, however. Given the reliance on task instructions to motivate participants to suppress target memories, such inconsistencies in SIF may reasonably owe to differences in compliance or expectations as to whether they will again need to retrieve those items (on, say, a final test). We tested these possibilities on a large (N = 497) sample of TNT participants. In addition to successfully replicating SIF, we found that the magnitude of the effect was significantly and negatively correlated with participants' reported compliance during the No-Think trials. This pattern held true on both same- and independent-probe measures of forgetting, as well as when the analysis was conditionalized on initial learning. In contrast, test expectancy was not associated with SIF. Supporting previous intuition and more limited post-hoc examinations, this study provides robust evidence that a lack of compliance with No-Think instructions significantly compromises SIF. As such, it suggests that diminished effects in some studies may owe, at least in part, to non-compliance—a factor that should be carefully tracked and/or controlled. Motivated forgetting is possible, provided that one is sufficiently motivated and capable of following the task instructions. [ABSTRACT FROM AUTHOR]

Traumatic brain injuries (TBI) of varied types are common across all populations and can cause visual problems. For military personnel in combat settings, injuries from blast exposures (bTBI) are prevalent and arise from a myriad of different situations. To model these diverse conditions, we are one of several groups modeling bTBI using mice in varying ways. Here, we report a refined analysis of retinal ganglion cell (RGC) damage in male C57BL/6J mice exposed to a blast-wave in an enclosed chamber. Ganglion cell layer thickness, RGC density (BRN3A and RBPMS immunoreactivity), cellular density of ganglion cell layer (hematoxylin and eosin staining), and axon numbers (paraphenylenediamine staining) were quantified at timepoints ranging from 1 to 17-weeks. RNA sequencing was performed at 1-week and 5-weeks post-injury. Earliest indices of damage, evident by 1-week post-injury, are a loss of RGC marker expression, damage to RGC axons, and increase in glial markers expression. Blast exposure caused a loss of RGC somas and axons—with greatest loss occurring by 5-weeks post-injury. While indices of glial involvement are prominent early, they quickly subside as RGCs are lost. The finding that axonopathy precedes soma loss resembles pathology observed in mouse models of glaucoma, suggesting similar mechanisms. [ABSTRACT FROM AUTHOR]

The mixed land covers encompassing bridges (MLB) are integral indicator of the socio-economic hydrological system, and their progressions are vital for flood risk assessment. However, most of the previous studies have neglected a thorough evaluation of MLBs (e.g., types, areas, and depths) on impacting flood vulnerability. This paper addresses this research gap by methodically assessing the spatial characteristics of MLBs in floodplains and their divergent impacts on flood vulnerability using four case studies of Alabama State in the USA. The hydrological and bridge data were synthesized from United States Geological Survey and National Bridge Inventory, respectively. A union of Hydrologic Engineering Center's-River Analysis System (HEC-RAS), Geographic Information System, and Surface Difference Model were employed to retrieve water surface profiles and floodplain assessments in MLBs. The results highlighted that the occurrence of floodplains was more correlated to flood depths compared to flood areas in the MLBs of Alabama. The spatial contribution of the diverse MLBs in producing deep (19%) and shallow (30%) flood depths in the bridges of Alabama were 49%, while medium flood depths were impacted only on 4% of the MLBs. The highest and lowest flood areas were noticed in the MLBs of pastures and mixed forests, respectively. Overall, the findings implied that the contribution of the individual MLBs in floodplains is multifaceted in the bridges of Alabama with spatially varying land cover distribution. Further, it is recommended that for assessing flood vulnerability, the stakeholders should focus not only on the MLBs but also on its spatially dynamic characteristics. [ABSTRACT FROM AUTHOR]

Sleep's role in memory consolidation is widely acknowledged, but its role in weakening memories is still debated. Memory weakening is evolutionary beneficial and makes an integral contribution to cognition. We sought evidence on whether sleep-based memory reactivation can facilitate memory suppression. Participants learned pairs of associable words (e.g., DIET–CREAM) and were then exposed to hint words (e.g., DIET) and instructed to either recall ("think") or suppress ("no-think") the corresponding target words (e.g., CREAM). As expected, suppression impaired retention when tested immediately after a 90-min nap. To test if reactivation could selectively enhance memory suppression during sleep, we unobtrusively presented one of two sounds conveying suppression instructions during sleep, followed by hint words. Results showed that targeted memory reactivation did not enhance suppression-induced forgetting. Although not predicted, post-hoc analyses revealed that sleep cues strengthened memory, but only for suppressed pairs that were weakly encoded before sleep. The results leave open the question of whether memory suppression can be augmented during sleep, but suggest strategies for future studies manipulating memory suppression during sleep. Additionally, our findings support the notion that sleep reactivation is particularly beneficial for weakly encoded information, which may be prioritized for consolidation. [ABSTRACT FROM AUTHOR]

Background: Acute osteomyelitis is typically caused by Gram-positive pathogens, commonly antibiotic-resistant Staphylococcus species. Standard antibiotic treatment is challenging due to required multiple daily doses, therapeutic drug monitoring, and parenteral administration for at least 4 weeks. Oritavancin is a long-acting lipoglycopeptide antibiotic approved as a single 1200 mg dose for the treatment of adult patients with acute bacterial skin and skin structure infections. Objective: To characterize the real-world use, efficacy, and safety of oritavancin in adult patients with acute osteomyelitis. Methods: This was a 2-year, multicenter, retrospective, descriptive study of patients treated for acute osteomyelitis with weekly doses of oritavancin. End of therapy evaluation (ETE) was defined as evaluation at 7–10 days after the last dose of oritavancin, and post-therapy assessment (PTE) was at 3 months and 6 months. At ETE and PTE, patients were interviewed via telephone for clinical outcomes, using a standard questionnaire. Electronic medical record review was also conducted. Results: 134 patients were treated with oritavancin for acute osteomyelitis across 20 different Metro Infectious Disease Consultants infusion centers in six states. Of total positive cultures, 71.9% (92/128) were methicillin-resistant Staphylococcus aureus (MRSA) from deep wounds, bone, or joint culture; an additional nine (6.7%) of 134 patients presented with concomitant MRSA bacteremia. Oritavancin was administered via intravenous catheter; patients received an initial treatment of 1200 mg and then 800 mg weekly thereafter for a total number of doses of four (n = 118) or five (n = 16). 118 patients (88.1%) of the baseline 134 patients achieved clinical success at the ETE timepoint. 130 patients were available for PTE at 3 months and 6 months. Overall, relapse or persistent infection was diagnosed in 13/134 (9.7%) patients. Nine (6.7%) of 134 patients were admitted to the hospital during the follow-up period but none for osteomyelitis. Adverse events were reported in five (3.7%) patients including hypoglycemia-related symptoms (three patients), tachycardia (one patient), and tachycardia with chest pain (one patient). None of these patients were hospitalized due to adverse events, and all patients eventually finished their treatment regimens. Conclusion: This is the largest real-world clinical study of adult patients treated with oritavancin for acute osteomyelitis. Use of oritavancin for acute osteomyelitis infection resulted in a high rate of positive clinical outcomes and a low incidence of adverse events, thereby providing potential for a convenient, effective, and safe therapeutic option. Future prospective and comparative studies are needed to validate these findings. [ABSTRACT FROM AUTHOR]

While some treatment options have seen limited success in relieving HPPD symptoms, self-resolution of HPPD symptoms cannot be entirely ruled out. Fluoxetine was started after symptom onset and had no effect on HPPD symptomatology; prior case reports document SSRI's both exacerbating and relieving HPPD symptoms (Halpern et al. [2]). Psychotic and Still Tripping - Hallucinogen Persisting Perception Disorder and First Break Psychosis in an Adolescent. [Extracted from the article]

For biosimilar drug development programs, it is essential to demonstrate that there are no clinically significant differences between the proposed biosimilar therapeutic (biosimilar) and its reference product (originator). Based on a stepwise comprehensive comparability exercise, the biosimilar must demonstrate similarity to the originator in physicochemical characteristics, biological activity, pharmacokinetics, efficacy, and safety, including immunogenicity. The goal of the immunogenicity assessment is to evaluate potential differences between the proposed biosimilar product and the originator product in the incidence and severity of human immune responses. Establishing that there are no clinically meaningful differences in the immune response between the products is a key element in the demonstration of biosimilarity. An issue of practical, regulatory, and financial importance is to establish whether a two-assay (based on the biosimilar and originator respectively) or a one-assay approach (based on the biosimilar) is optimal for the comparative immunogenicity assessment. This paper recommends the use of a single, biosimilar-based assay for assessing immunogenic similarity in support of biosimilar drug development. The development and validation of an ADA assay used for a biosimilar program should include all the assessments recommended for an innovator program (10–16, 29). In addition, specific parameters also need to be evaluated, to gain confidence that the assay can detect antibodies against both the biosimilar and the originator. Specifically, the biosimilar and the originator should be compared in antigenic equivalence, to assess the ability of the biosimilar and the originator to bind in a similar manner to the positive control(s), as well as in the confirmatory assay and drug tolerance experiments. Practical guidance for the development and validation of anti-drug antibody (ADA) assays to assess immunogenicity of a biosimilar in comparison to the originator, using the one-assay approach, are described herein. [ABSTRACT FROM AUTHOR]

Given a Riemannian 3-ball (B ¯ , g) of nonnegative scalar curvature, Bartnik conjectured that (B ¯ , g) admits an asymptotically flat (AF) extension (without horizons) of the least possible ADM mass and that such a mass minimizer is an AF solution to the static vacuum Einstein equations, uniquely determined by natural geometric conditions on the boundary data of (B ¯ , g) . We prove the validity of the second statement, i.e., such mass minimizers, if they exist, are indeed AF solutions of the static vacuum equations. On the other hand, we prove that the first statement is not true in general; there is a rather large class of bodies (B ¯ , g) for which a minimal mass extension does not exist. [ABSTRACT FROM AUTHOR]

We introduce an elliptic regularization of the PDE system representing the isometric immersion of a surface in R3. The regularization is geometric and has a natural variational interpretation. [ABSTRACT FROM AUTHOR]

Due to the complex circuitry and plethora of cell types involved in somatosensation, it is becoming increasingly important to be able to observe cellular activity at the population level. In addition, since cells rely on an intricate variety of extracellular factors, it is important to strive to maintain the physiological environment. Many electrophysiological techniques require the implementation of artificially-produced physiological environments and it can be difficult to assess the activity of many cells simultaneously. Moreover, imaging Ca2+ transients using Ca2+-sensitive dyes often requires in vitro preparations or in vivo injections, which can lead to variable expression levels. With the development of more sensitive genetically-encoded Ca2+ indicators (GECIs) it is now possible to observe changes in Ca2+ transients in large populations of cells at the same time. Recently, groups have used a GECI called GCaMP to address fundamental questions in somatosensation. Researchers can now induce GCaMP expression in the mouse genome using viral or gene knock-in approaches and observe the activity of populations of cells in the pain pathway such as dorsal root ganglia (DRG), spinal neurons, or glia. This approach can be used in vivo and thus maintains the organism’s biological integrity. The implementation of GCaMP imaging has led to many advances in our understanding of somatosensation. Here, we review the current findings in pain research using GCaMP imaging as well as discussing potential methodological considerations. [ABSTRACT FROM AUTHOR]

Intrusive memories, images, and hallucinations are hallmark symptoms of psychiatric disorders. Although often attributed to deficient inhibitory control by the prefrontal cortex, difficulty in controlling intrusive thoughts is also associated with hippocampal hyperactivity, arising from dysfunctional GABAergic interneurons. How hippocampal GABA contributes to stopping unwanted thoughts is unknown. Here we show that GABAergic inhibition of hippocampal retrieval activity forms a key link in a fronto-hippocampal inhibitory control pathway underlying thought suppression. Subjects viewed reminders of unwanted thoughts and tried to suppress retrieval while being scanned with functional magnetic resonance imaging. Suppression reduced hippocampal activity and memory for suppressed content. 1H magnetic resonance spectroscopy revealed that greater resting concentrations of hippocampal GABA predicted better mnemonic control. Higher hippocampal, but not prefrontal GABA, predicted stronger fronto-hippocampal coupling during suppression, suggesting that interneurons local to the hippocampus implement control over intrusive thoughts. Stopping actions did not engage this pathway. These findings specify a multi-level mechanistic model of how the content of awareness is voluntarily controlled. [ABSTRACT FROM AUTHOR]

Hybrid sol-gel inorganic-organic fibres offer great potential in tissue engineering and regenerative medicine. A significant challenge is to process them using scalable technologies into useful scaffolds that provide control over fibre diameter, morphology, mechanical properties, ion release, degradation and cell response. In this work we develop formulations that are amenable to processing via solution blow spinning (SBS), a rapid technique using simple equipment to spray nano-/micro-fibres without any electric fields. The technique is extended to produce porous class I and II hybrid fibres using cryogenic SBS, with formulations developed based on tetraethyl orthosilicate/gelatin that are relatively facile to lyophilise. The formulations developed here take advantage of the reversible thermally activated conformation change of gelatin in aqueous solutions from random coil to triple helix to enable viscosity tuning and therefore fibre spinning. Gelatin is functionalised with (3-glycidyloxypropyl)trimethoxysilane to produce class II hybrids which exhibit controllable time- and temperature-dependent viscosity profiles which can be tuned for spinning into highly porous fibres. [ABSTRACT FROM AUTHOR]

Understanding and predicting crystal growth is fundamental to the control of functionality in modern materials. Despite investigations for more than one hundred years, it is only recently that the molecular intricacies of these processes have been revealed by scanning probe microscopy. To organize and understand this large amount of new information, new rules for crystal growth need to be developed and tested. However, because of the complexity and variety of different crystal systems, attempts to understand crystal growth in detail have so far relied on developing models that are usually applicable to only one system. Such models cannot be used to achieve the wide scope of understanding that is required to create a unified model across crystal types and crystal structures. Here we describe a general approach to understanding and, in theory, predicting the growth of a wide range of crystal types, including the incorporation of defect structures, by simultaneous molecular-scale simulation of crystal habit and surface topology using a unified kinetic three-dimensional partition model. This entails dividing the structure into 'natural tiles' or Voronoi polyhedra that are metastable and, consequently, temporally persistent. As such, these units are then suitable for re-construction of the crystal via a Monte Carlo algorithm. We demonstrate our approach by predicting the crystal growth of a diverse set of crystal types, including zeolites, metal-organic frameworks, calcite, urea and l-cystine. [ABSTRACT FROM AUTHOR]

Abstract A novel aqueous silica removal process using naturally occurring diatoms for water and wastewater treatment, in particular water reuse and desalination, was developed. Brackish agricultural drainage water containing 39 mg L of total silica and 10 g L of total dissolved solids was used as a source of silica-assimilating diatoms. The drainage water was statically incubated in 500-mL and 7.5-L photobioreactors at 27 ± 2 °C under continuous illumination using two 13-W compact fluorescent light bulbs as a light source. After 10 days, brown algal biomass became noticeable and silica removal started to occur. Silica removal accelerated as algal biomass accumulated. In the fourth semi-batch cycle, more than 95 % of molybdate reactive silica was removed within 28 h. Removal of nonreactive silica was also confirmed. Reverse osmosis concentrate samples from advanced water reclamation facilities with high silica concentration (>120 mg L) were also tested. More than 75 % of silica was removed within 6 days. Microscopic analysis revealed the presence of Pseudostaurosira, Nitzschia, and Halamphora species in the photobioreactors. To the best of our knowledge, this is the first report on the use of diatoms for aqueous silica removal in water treatment. [ABSTRACT FROM AUTHOR]

Negative biases in cognition have been documented consistently in major depressive disorder (MDD), including difficulties in the ability to control the processing of negative material. Although negative information-processing biases have been studied using both behavioral and neuroimaging paradigms, relatively little research has been conducted examining the difficulties of depressed persons with inhibiting the retrieval of negative information from long-term memory. In this study, we used the think/no-think paradigm and functional magnetic resonance imaging to assess the cognitive and neural consequences of memory suppression in individuals diagnosed with depression and in healthy controls. The participants showed typical behavioral forgetting effects, but contrary to our hypotheses, there were no differences between the depressed and nondepressed participants or between neutral and negative memories. Relative to controls, depressed individuals exhibited greater activity in right middle frontal gyrus during memory suppression, regardless of the valence of the suppressed stimuli, and differential activity in the amygdala and hippocampus during memory suppression involving negatively valenced stimuli. These findings indicate that depressed individuals are characterized by neural anomalies during the suppression of long-term memories, increasing our understanding of the brain bases of negative cognitive biases in MDD. [ABSTRACT FROM AUTHOR]

This study explored the role of student (e.g., age, language background, gender), home (e.g., parent/caregiver education), and school (e.g., school type, size) socio-demographic factors in students' school (e.g., in-school arts tuition, arts engagement), home (e.g., parent/caregiver-child arts interaction), and community (e.g., arts attendance, arts tuition) arts participation. The sample comprised 1172 elementary and secondary school students from 15 schools. Findings revealed that student and home socio-demographic factors were the most salient in predicting arts participation across school, home, and community contexts. Age, gender, and prior achievement were the key student socio-demographic factors, while parent/caregiver education and occupation were also associated with students' arts participation. Implications for practice and intervention pertinent to young people's arts participation are discussed. [ABSTRACT FROM AUTHOR]

We study the existence and uniqueness of solutions to the static vacuum Einstein equations in bounded domains, satisfying the Bartnik boundary conditions of prescribed metric and mean curvature on the boundary. [ABSTRACT FROM AUTHOR]

Introduction: Limited data exist on patient factors related to environmental contamination with Clostridium difficile. Methods: We evaluated the association between the functional status of patients with C. difficile infection (CDI) and environmental contamination with C. difficile. Results: Contamination of patient rooms was frequent and higher functional status was associated with contaminated surfaces remote from the bed. All but one environmental isolates matched the corresponding patient's stool isolate for the seven patients tested. Conclusion: Functional status is a factor that influences environmental contamination with C. difficile. Future studies should evaluate strategies to reduce contamination in CDI patient rooms, taking into account the patient's functional status. [ABSTRACT FROM AUTHOR]

This paper presents a hybrid baseline (HBL) navigation method for autonomous underwater vehicles (AUVs). In this approach, a floating acoustic transponder is used to augment moving short baseline (MSBL) navigation, in which two transponders are mounted on a source ship. Kinematic information regarding the floating buoy and source ship are communicated via acoustic messages to the AUV fleet. Simultaneously, clock synchronization and a predefined broadcast cycle enables transponder-to-AUV range estimates based on the acoustic message time-of-flight. Using the extended Kalman (EKF) filter formulation, the broadcasted kinematic information and acoustic ranges are combined onboard each AUV in the fleet to estimate the states of the source ship, the floating transponder, and the AUV itself. Simulation was used to optimize the configuration and performance of the HBL navigation, and field tests were performed to evaluate the navigational performance. In post-processing, high-accuracy position and timing data for the source ship and floating buoy was added to the onboard navigation data in an EKF to recreate the path of the AUV. The accuracy of this post-mission localization was evaluated relative to AUV positions independently measured by an acoustic tracking array at the test facility. The resulting AUV position estimation showed a mean error of 1.59 m, an improvement over the previous result (using MSBL navigation only) of 3.30 m. [ABSTRACT FROM AUTHOR]

Purpose: Freshwater lakes and reservoirs can produce substantial quantities of methane (CH) within bottom sediments. Due to its low solubility in water, CH forms bubbles that accumulate within bottom sediments and are released from sediments when buoyant forces exceed viscous, frictional, and inertial forces. Methane ebullition can enhance internal loading of nutrients and hasten release of other sediment-associated contaminants while also exporting a significant amount of C out of the lake basin and delivering a potent greenhouse gas to the atmosphere. The purpose of this study was to evaluate use of hydroacoustic measurements to remotely sense the CH content of sediments in lakes. Materials and methods: The acoustic signatures of bottom sediments measured using a BioSonics DT-X echosounder at 38, 201, and 430 kHz were compared with gas volumes of surficial sediments determined using a displacement method. Measurements were made on three lakes in southern California, USA that varied in depth, productivity, and other features. Results and discussion: The maximum volume backscatter strength of bottom echoes at 201 kHz was highly correlated with gas content ( r = 0.93) and, with suitable ground-truthing, can quantify the concentration and spatial distribution of CH gas in soft cohesive sediments of lakes and reservoirs. As an application of this technique, the spatial distribution of CH within bottom sediments of Lake Elsinore was determined from a hydroacoustic survey conducted in June 2010. Results are also presented from a transect on Lake Hodges demonstrating high levels of CH in this eutrophic lake. Conclusions: Hydroacoustic measurements of the maximum volume backscatter strength of soft organic sediments at 201 kHz provide a way to remotely estimate the volume of methane and other gases present in bottom sediments of lakes and reservoirs. [ABSTRACT FROM AUTHOR]

Remembering a past experience can, surprisingly, cause forgetting. Forgetting arises when other competing traces interfere with retrieval and inhibitory control mechanisms are engaged to suppress the distraction they cause. This form of forgetting is considered to be adaptive because it reduces future interference. The effect of this proposed inhibition process on competing memories has, however, never been observed, as behavioral methods are 'blind' to retrieval dynamics and neuroimaging methods have not isolated retrieval of individual memories. We developed a canonical template tracking method to quantify the activation state of individual target memories and competitors during retrieval. This method revealed that repeatedly retrieving target memories suppressed cortical patterns unique to competitors. Pattern suppression was related to engagement of prefrontal regions that have been implicated in resolving retrieval competition and, critically, predicted later forgetting. Thus, our findings demonstrate a cortical pattern suppression mechanism through which remembering adaptively shapes which aspects of our past remain accessible. [ABSTRACT FROM AUTHOR]