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Down syndrome (DS) is a common genetic condition caused by trisomy of chromosome 21. Among their complex clinical features, including musculoskeletal, neurological, and cardiovascular disabilities, individuals with DS have an increased risk of developing progressive dementia and early-onset Alzheimer's disease (AD). This dementia is attributed to the increased gene dosage of the amyloid-β (Aβ) precursor protein gene, the formation of self-propagating Aβ and tau prion conformers, and the deposition of neurotoxic Aβ plaques and tau neurofibrillary tangles. Tau amyloid fibrils have previously been established to adopt many distinct conformations across different neurodegenerative conditions. Here, we report the characterization of brain samples from four DS cases spanning 36–63 years of age by spectral confocal imaging with conformation-specific dyes and cryo–electron microscopy (cryo-EM) to determine structures of isolated tau fibrils. High-resolution structures revealed paired helical filament (PHF) and straight filament (SF) conformations of tau that were identical to those determined from AD cases. The PHFs and SFs are made of two C-shaped protofilaments, each containing a cross-β/β-helix motif. Similar to filaments from AD cases, most filaments from the DS cases adopted the PHF form, while a minority (approximately 20%) formed SFs. Samples from the youngest individual with no documented dementia had sparse tau deposits. To isolate tau for cryo-EM from this challenging sample we used a novel affinity-grid method involving a graphene oxide surface derivatized with anti-tau antibodies. This method improved isolation and revealed that primarily tau PHFs and a minor population of chronic traumatic encephalopathy type II–like filaments were present in this youngest case. These findings expand the similarities between AD and DS to the molecular level, providing insight into their related pathologies and the potential for targeting common tau filament folds by small-molecule therapeutics and diagnostics. [ABSTRACT FROM AUTHOR]

Shrub willow (Salix spp.) is a potential source of biomass feedstock for bioenergy, biofuels, and other bioproducts, but, to be considered sustainable, production systems must not result in long-term degradation of soil resources. Shrub willows are expected to reduce soil loss and improve soil health over time, but data are lacking to model soil erosion from shrub willow cropping systems. Our objectives were to characterize shrub willow across a chronosequence of age classes and to use these data to parameterize the Revised Universal Soil Loss Equation (RUSLE2) and model estimated soil loss from a range of soil types, slopes, management practices, and willow cultivars. Predicted average annual soil loss from shrub willow over seven 3-year rotations ranged from 1.68 to 1.97 Mg ha−1 yr−1, below the estimated soil loss tolerance value (T = 6.7 Mg ha−1 yr−1). Steeper slopes and silty soils were more susceptible to soil loss, but soil loss estimates across the production cycle were consistently below T. However, in all cases, the first year of production resulted in predicted soil loss above T (11–17 Mg ha−1 yr−1 under typical growing conditions). Soil disturbance during site preparation and planting and the lack of cover until canopy closure in the second year of production leave the soil susceptible to erosion in the first growing season. Cover crops, if they do not interfere with the growth of the willow crop, may reduce risk to the soil and provide additional benefits. [ABSTRACT FROM AUTHOR]

Background: Sub-Saharan Africa (SSA) has the highest cervical cancer (CC) burden globally—worsened by its HIV epidemics. In 2020, the World Health Organization (WHO) introduced a CC elimination strategy with goals for vaccination, screening, and treatment. To benchmark progress, we examined temporal trends in screening coverage, percent screened at least twice by the age of 45, screening coverage among women living with HIV (WLHIV), and pre-cancer treatment coverage in SSA. Methods and findings: We conducted a systematic analysis of cross-sectional population-based surveys. It included 52 surveys from 28 countries (2000 to 2020) with information on CC screening among women aged 25 to 49 years (N = 151,338 women). We estimated lifetime and past 3-year screening coverage by age, year, country, and HIV serostatus using a Bayesian multilevel model. Post-stratification and imputations were done to obtain aggregate national, regional, and SSA-level estimates. To measure re-screening by age 45, a life table model was developed. Finally, self-reported pre-cancer treatment coverage was pooled across surveys using a Bayesian meta-analysis. Overall, an estimated 14% (95% credible intervals [95% CrI]: 11% to 21%) of women aged 30 to 49 years had ever been screened for CC in 2020, with important regional and country-level differences. In Eastern and Western/Central Africa, regional screening coverages remained constant from 2000 to 2020 and WLHIV had greater odds of being screened compared to women without HIV. In Southern Africa, however, screening coverages increased and WLHIV had equal odds of screening. Notably this region was found to have higher screening coverage in comparison to other African regions. Rescreening rates were high among women who have already been screened; however, it was estimated that only 12% (95% CrI: 10% to 18%) of women had been screened twice or more by age 45 in 2020. Finally, treatment coverage among 4 countries with data was 84% (95% CrI: 70% to 95%). Limitations of our analyses include the paucity of data on screening modality and the few countries that had multiple surveys. Conclusion: Overall, CC screening coverage remains sub-optimal and did not improve much over the last 2 decades, outside of Southern Africa. Action is needed to increase screening coverage if CC elimination is to be achieved. Lily Yang and team analyze data from 28 countries to estimate cervical cancer screening coverage by age, HIV status, country, and region. Author summary: Why was this study done?: Cervical cancer (CC) is one of the leading causes of cancer death in sub-Saharan Africa (SSA), where CC burden is worsened by HIV epidemics. In 2020, the World Health Organization (WHO) announced its global strategy for the elimination of CC as a public health threat with targets for vaccination, screening, and treatment. Given that large cohorts of women remain unprotected by vaccines, we sought to monitor temporal trends in CC screening coverage, screening coverage by HIV status, rates of re-screening, and pre-cancer treatment coverage. What did the researchers do and find?: We systematically analyzed and extracted data from 52 population-based surveys across 28 countries and used a multilevel Bayesian modeling framework to estimate CC screening coverage by age, HIV status, country, and region. We also examined the proportion of women screened twice by the age of 45 and cervical pre-cancer treatment coverage. Overall, only 1 in 7 women aged 30 to 49 years were estimated to have been ever screened for CC in 2020. Over 2000 to 2020, we found that CC screening coverage increased in Southern African but not much in Eastern and Western/Central Africa. Women living with HIV were more likely to be screened than women without HIV in all regions except Southern Africa. In 2020, 1 in 8 women were estimated to have been screened at least twice by the age of 45, much lower than the 70% target. Among the 4 countries with information on pre-cancer treatment coverage, 84% of women who received a positive CC test were estimated to have undergone pre-cancer treatment. What do these findings mean?: Most women are not being reached by CC screening programs and none of the countries have reached WHO's targets for CC screening. Alongside expansion of HPV vaccination programs, action needs to be taken to improve and address barriers towards screening, including strengthening data collection systems, if CC is to be eliminated. [ABSTRACT FROM AUTHOR]

Decentering whiteness and decolonizing educational research is not a simple matter for researchers who may (initially) be unaware of their social locations. This paper begins by describing the three authors' individual work within indigenous populations and subsequently explores the impact of their critical journey together as a community of scholars working to decolonize their research practice. Following an overview of their individual stories, the authors share principles of ethical scholarly engagement within indigenous communities, particularly positionality, ownership, and answerability, that they hope will be valuable to others who may embark upon similar critically reflective journeys. Alongside each of these principles, they pose "unanswered questions" so as not to uphold their journey as a model, but rather to illuminate how this work is messy, challenging, eye-opening, unsettling, and ongoing. The authors conclude that it is the "methodological responsibility" of white scholars to do the ethical work to understand, untangle, and dismantle potentially harmful dispositions, orientations, and practices before engaging with indigenous communities, and suggest that such transformation may be most powerfully pursued in a purposeful and collaborative space. [ABSTRACT FROM AUTHOR]

Background: To compare the efficacy and safety of follitropin delta in its individualized fixed-dose regimen with follitropin alfa in a conventional adjustable dosing regimen in Chinese women. Methods: This was a subgroup analysis of the randomized, multi-center, assessor-blind, non-inferiority trial (GRAPE) including 759 Chinese women (aged 20–40 years) recruited in 16 reproductive medicine clinics in China. Women were randomized in a 1:1 ratio to be treated with either follitropin delta dose based on anti-Müllerian hormone (AMH) and body weight or conventional dosing with follitropin alfa following a gonadotropin-releasing hormone (GnRH) antagonist protocol. The primary outcome was ongoing pregnancy rate assessed 10–11 weeks after embryo transfer in the fresh cycle (non-inferiority margin -10.0%). Results: 378 in the follitropin delta group and 381 in the follitropin alfa group were randomized and exposed. Non-inferiority was confirmed with respect to ongoing pregnancy with rates of 31.0% vs. 25.7% for follitropin delta compared to follitropin alfa, estimated mean difference of 5.1% (95% confidence interval (CI) -1.3% to 11.5%). The clinical pregnancy rate (35.4% vs. 31.5%, P = 0.239) and live birth rate (31.0% vs. 25.5%, P = 0.101) were comparable between the follitropin delta group and the follitropin alfa group. Overall, the individualized follitropin delta treatment resulted in fewer oocytes retrieved compared to follitropin alfa treatment (10.3 ± 6.2 vs. 12.5 ± 7.5, P < 0.001), which was mainly due to fewer oocytes (10.5 ± 6.4 vs. 13.9 ± 7.8) in women with AMH ≥ 15 pmol/L. Accordingly there was a lower incidence of early ovarian hyper-stimulation syndrome (OHSS) and/or preventive interventions (6.1% vs. 11.0%, P = 0.013). A daily follitropin delta dose of 10.2 µg (95% CI: 9.3—11.2 µg) was estimated to provide the same number of oocytes retrieved as a starting dose of 150 IU/d of follitropin alfa. Conclusion: Follitropin delta in its individualized fixed-dose regimen showed similar efficacy and improved safety compared with follitropin alfa in a conventional adjustable dosing regimen in Chinese women. Clinical trial registration number: NCT03296527. [ABSTRACT FROM AUTHOR]

Interspecies transmission of influenza A virus (IAV) between pigs and people represents a threat to both animal and public health. To better understand the risks of influenza transmission at the human–animal interface, we evaluated 1) the rate of IAV detection in swine farmworkers before and after work during two human influenza seasons, 2) assessed risk factors associated with IAV detection in farmworkers and 3) characterized the genetic sequences of IAV detected in both workers and pigs. Of 58 workers providing nasal passage samples during 8‐week periods during the 2017/18 and 2018/19 influenza seasons, 33 (57%) tested positive by rRT‐PCR at least once. Sixteen (27%) workers tested positive before work and 24 (41%) after work. At the sample level, 58 of 1,785 nasal swabs (3.2%) tested rRT‐PCR positive, of which 20 of 898 (2.2%) were collected prior to work and 38 of 887 (4.3%) after work. Although farmworkers were more likely to test positive at the end of the working day (OR = 1.98, 95% CI 1.14–3.41), there were no influenza‐like illness (ILI) symptoms, or other risk indicators, associated with IAV detection before or after reporting to work. Direct whole‐genome sequencing from samples obtained from worker nasal passages indicated evidence of infection of a worker with pandemic 2009 H1N1 of human‐origin IAV (H1‐pdm 1A 3.3.2) when reporting to work, and exposure of several workers to a swine‐origin IAV (H1‐alpha 1A 1.1) circulating in the pigs on the farm where they were employed. Our study provides evidence of 1) risk of IAV transmission between pigs and people, 2) pandemic H1N1 IAV infected workers reporting to work and 3) workers exposed to swine harbouring swine‐origin IAV in their nasal passages temporarily. Overall, our results emphasize the need to implement surveillance and transmission preventive protocols at the pig/human interface. [ABSTRACT FROM AUTHOR]

Postoperative loss of breast volume represents a significant parameter for outcome evaluation of breast reconstruction. Breast volume broadly varies- depending of reconstruction method as well as surgical differences. A structural pattern of breast volume loss provides an essential parameter for preoperative design, helps to reduce postoperative breast asymmetry rate and thereby the need for reoperation. Therefore we hereby compare volume change of the three main reconstruction techniques: autologous flap-based, prosthesis-based and autologous fat transplantation breast reconstruction. Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

The pharmacological blockade of P2X4 receptors has shown potential benefits in the management of several immune/inflammatory diseases. However, data regarding the involvement of P2X4 receptors in the pathophysiological mechanisms of action in intestinal inflammation are not well defined. We aimed to evaluate the anti-inflammatory effects of two novel and selective P2X4 receptor antagonists, NC-2600 and NP-1815-PX, and characterize the molecular mechanisms of their action in a murine model of 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis. These two drugs and dexamethasone (DEX) were administered orally for 6 days, immediately after the manifestation of DNBS. The body weight decrease, resulting from colitis, was attenuated by NC-2600 and NP-1815-PX, but not DEX. However, all three drugs attenuated the increase in spleen weight and ameliorated macroscopic and microscopic colonic tissue damage. Furthermore, all three compounds decreased tissue IL-1β levels and caspase-1 expression and activity. Colonic tissue increase of tumor necrosis factor was downregulated by DEX, while both NC-2600 and NP-1815-PX were ineffective. The reduction of occludin associated with colitis was ameliorated by NC-2600 and NP-1815-PX, but not DEX. In THP-1 cells, lipopolysaccharide and ATP upregulated IL-1β release and NLRP3, caspase-1, caspase-5, and caspase-8 activity, but not of caspase-4. These changes were prevented by NC-2600 and NP-1815-PX treatment. For the first time, the above findings show that the selective inhibition of P2X4 receptors represents a viable approach to manage bowel inflammation via the inhibition of NLRP3 inflammasome signaling pathways. [ABSTRACT FROM AUTHOR]

Pathogen transmission depends on host density, mobility and contact. These components emerge from host and pathogen movements that themselves arise through interactions with the surrounding environment. The environment, the emergent host and pathogen movements, and the subsequent patterns of density, mobility and contact form an 'epidemiological landscape' connecting the environment to specific locations where transmissions occur. Conventionally, the epidemiological landscape has been described in terms of the geographical coordinates where hosts or pathogens are located. We advocate for an alternative approach that relates those locations to attributes of the local environment. Environmental descriptions can strengthen epidemiological forecasts by allowing for predictions even when local geographical data are not available. Environmental predictions are more accessible than ever thanks to new tools from movement ecology, and we introduce a 'movement‐pathogen pace of life' heuristic to help identify aspects of movement that have the most influence on spatial epidemiology. By linking pathogen transmission directly to the environment, the epidemiological landscape offers an efficient path for using environmental information to inform models describing when and where transmission will occur. [ABSTRACT FROM AUTHOR]

Bone tissue engineering (BTE) is a promising method for the repair of difficult-to-heal bone tissue damage by providing three-dimensional structures for cell attachment, proliferation, and differentiation. Traditional Chinese medicine (TCM) has been introduced as an effective global medical program by the World Health Organization, comprising intricate components, and promoting bone regeneration by regulating multiple mechanisms and targets. This study outlines the potential therapeutic capabilities of TCM combined with BTE in bone regeneration. The effective active components promoting bone regeneration can be generally divided into flavonoids, alkaloids, glycosides, terpenoids, and polyphenols, among others. The chemical structures of the monomers, their sources, efficacy, and mechanisms are described. We summarize the use of compounds and medicinal parts of TCM to stimulate bone regeneration. Finally, the limitations and prospects of applying TCM in BTE are introduced, providing a direction for further development of novel and potential TCM. [ABSTRACT FROM AUTHOR]

Time-resolved studies with temporal resolution that separate molecular level dynamics from macroscopic changes, allow clear distinction between the time scales of the different degrees of freedom involved. Cooperative molecular switching in the solid state is exemplified by spin crossover phenomenon in crystals of transition metal complexes. Here we show the existence of a delay between the crystalline volume increase, and the cooperative macroscopic switching of molecular state. Using 100 ps X-ray diffraction, we track the molecular spin state and the structure of the lattice during the photoinduced low spin to high spin transition in microcrystals of [FeIII(3-MeO-SalEen)2]PF6. Model simulations explain the phenomenon with thermally activated kinetics governed by local energy barriers separating the molecular states. Such behaviour is different from that encountered in materials with no local energy barriers, where phase transformation can occur simultaneously with propagation of strain. Broadly, this motivates an optimised material design, scalable with size and intrinsic energetics. Ultrafast methods have the ability to transiently decouple transitions between subsystems that evolve simultaneously at thermal equilibrium. Here, time-resolved X-ray diffraction reveals a time delay between volumetric and spin-state switching in a spin-crossover compound. [ABSTRACT FROM AUTHOR]

Because breast augmentation is one of the most popular cosmetic procedures, the issue of implant-related complications has been widely debated ever since the FDA approved the use of implants in 1962. Although decades have passed, breast implant illness (BII) still represents a poorly defined and controversial complication. With ongoing nonscientific discussion in the mainstream media and on social media, revealing the etiology of BII is urgent because knowledge of this subject ultimately influences patients' decisions. Little or no scientific research is currently available on BII and no final conclusions regarding its etiology, clinical manifestations, diagnostic criteria, or treatment have been made. This review aims to give an overview of the hypotheses on the etiology of BII and seeks inspiration to improve the conditions of BII patients. [ABSTRACT FROM AUTHOR]

In this work, we address structural, iconic and social dimensions of the emergence of phonological systems in two emerging sign languages. A comparative analysis is conducted of data from a village sign language (Central Taurus Sign Language; CTSL) and a community sign language (Nicaraguan Sign Language; NSL). Both languages are approximately 50 years old, but the sizes and social structures of their respective communities are quite different. We find important differences between the two languages' handshape inventories. CTSL's handshape inventory has changed more slowly than NSL's across the same time period. In addition, while the inventories of the two languages are of similar size, handshape complexity is higher in NSL than in CTSL. This work provides an example of the unique and important perspective that emerging sign languages offer regarding longstanding questions about how phonological systems emerge. [ABSTRACT FROM AUTHOR]

Background: Abuse of opioids among children and adolescents has become a major public concern in the United States. Understanding the epidemiology of opioid use in this vulnerable population is critical to address opioid abuse. Objective: The aim of this study is to characterize opioid use for the treatment of acute pain among children and adolescents enrolled in Mississippi Medicaid and to determine the effects of related clinical factors (ie, mental health disorders and obstructive sleep apnea [OSA] on patterns of opioid use. Methods: A retrospective cohort study was conducted using the Mississippi Medicaid administrative claims data from October 2015 through December 2017. We examined the proportion of children and adolescents less than 21 years of age using opioids within 7 days following any qualifying acute pain episode, as well as the difference in opioid use patterns between individuals with various demographic and clinical characteristics. Results: Over 5% of the eligible population received opioids within 7 days of a qualifying pain episode. The majority received schedule II or schedule III to IV short-acting opioids. There was no significant difference in opioid use for acute pain between individuals with and without a mental health disorder. Opioid use for acute pain was significantly more likely among those with a history of OSA than those without OSA. Conclusion: This study characterizes the nature and patterns of opioid use among children and adolescents with acute pain. Further research is needed to understand the role of clinical and other demographic factors in the prescribing of opioids for acute pain in this population. [ABSTRACT FROM AUTHOR]

In this work, the thermoelectric properties of Cu‐Sb system compounds have been investigated to understand their relation with the electronic structures. The approach used is a theoretical one that combines the density functional theory, the Boltzmann transport theory, and the quantum theory of atoms in molecules. The results show that the Seebeck effect in metallic systems originates from the existence of various types of chemical bonds. However, this feature is not sufficient enough to generate effective thermoelectric effect. As in semi‐conducting compounds, the intrinsic driving force for thermoelectric effect remains the variation of the density of states near the Fermi level. [ABSTRACT FROM AUTHOR]

Although breast surgeries for aesthetic or reconstructive purposes are regularly performed, no focus has been laid on establishing an adequate and reliable volumetry method. While CT and MRI scan represent methods that are already in clinical use, the 3D scan is a novel and promising tool, easy to use with the possibility to measure the anatomic breast volume in an upright position. Nevertheless, its reliability is broadly underinvestigated. Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Objective Exercise programs to improve upper extremity function following stroke in the community setting are needed as the length of hospital stay continues to decrease. However, little has been done to increase understanding of how to translate an evidence-based rehabilitation intervention to real-world programs. The purpose of this case report was to describe a process evaluation of the implementation of an evidence-based upper extremity rehabilitation intervention for stroke, the Graded Repetitive Arm Supplementary Program, in a community setting. Methods (Case Description) A partnership between a nonprofit support organization and a local community center was established to deliver the program in the community. The Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework with mixed methods was used to evaluate the implementation. Results Reach: Twenty people were screened, 14 people met eligibility requirements, and 13 consented to participate. The program reached approximately 1.25% of the potential target population. Effectiveness: Participants with stroke demonstrated significant improvement in upper extremity function and quality of life as measured by the Fugl-Meyer Assessment for upper extremity, Action Research Arm Test, Rating of Everyday Arm-use in the Community and Home Scale, and Stroke Impact Scale. Adoption: Factors that facilitated program uptake were the well-planned implementation and the workplace coaching based on the audit results. Factors contributing to ongoing participation were the social support within the group environment and the instructor's capability of engaging the group. Implementation: A partnership between a nonprofit organization and a local community center was successfully established. The program was implemented as intended as verified by a fidelity checklist. Participant adherence was high as confirmed by the average attendance and practice time. Maintenance: Both the partner organization and community center continued to offer the program. Conclusion The Graded Repetitive Arm Supplementary Program had good fidelity of the critical principles and core components and was effective in improving upper extremity function and quality of life. Impact This partnership model may serve as the first step for future larger-scale implementation and could be used to move other stroke rehabilitation interventions into community settings. [ABSTRACT FROM AUTHOR]

The neural plasticity underlying language learning is a process rather than a single event. However, the dynamics of training‐induced brain reorganization have rarely been examined, especially using a multimodal magnetic resonance imaging approach, which allows us to study the relationship between functional and structural changes. We focus on sign language acquisition in hearing adults who underwent an 8‐month long course and five neuroimaging sessions. We assessed what neural changes occurred as participants learned a new language in a different modality—as reflected by task‐based activity, connectivity changes, and co‐occurring structural alterations. Major changes in the activity pattern appeared after just 3 months of learning, as indicated by increases in activation within the modality‐independent perisylvian language network, together with increased activation in modality‐dependent parieto‐occipital, visuospatial and motion‐sensitive regions. Despite further learning, no alterations in activation were detected during the following months. However, enhanced coupling between left‐lateralized occipital and inferior frontal regions was observed as the proficiency increased. Furthermore, an increase in gray matter volume was detected in the left inferior frontal gyrus which peaked at the end of learning. Overall, these results showed complexity and temporal distinctiveness of various aspects of brain reorganization associated with learning of new language in different sensory modality. [ABSTRACT FROM AUTHOR]

The mechanisms by which organisms control the stability of amorphous calcium carbonate (ACC) are yet not fully understood. Previous studies have shown that the intrinsic properties of ACC and its environment are critical in determining ACC stability. Here, the question, what is the effect of bulk incorporation versus surface adsorption of additives on the stability of synthetic ACC, is addressed. Using a wide range of in situ characterization techniques, it is shown that surface adsorption of poly(Aspartic acid) (pAsp) has a much larger stabilization effect than bulk incorporation of pAsp and only 1.5% pAsp could dramatically increase the crystallization temperature from 141 to 350 °C. On the contrary, surface adsorption of PO43− ions and OH− ions does not effectively stabilize ACC. However, bulk incorporation of these ions could significantly improve the ACC stability. It is concluded that the stabilization mechanism of pAsp is entirely different from that of PO43− and OH− ions: while pAsp is effectively inhibiting calcite nucleation at the surface of ACC particle, the latter acts to modify the ion mobility and delay crystal propagation. Thus, new insights on controlling the stability and crystallization processes of metastable amorphous materials are provided. [ABSTRACT FROM AUTHOR]

There has been little surveillance of influenza A viruses (IAVs) circulating in swine at live animal markets, particularly in the United States. To address this gap, we conducted active surveillance of IAVs in pigs, the air, and the environment during a summer and winter season in a live animal market in St. Paul, Minnesota, that had been epidemiologically associated with swine‐origin influenza cases in humans previously. High rates of IAV were detected by PCR in swine lungs and oral fluids during both summer and winter seasons. Rates of IAV detection by PCR in the air were similar during summer and winter, although rates of successful virus isolation in the air were lower during summer than in winter (26% and 67%, respectively). H3N2 was the most prevalent subtype in both seasons, followed by H1N2. Genetically diverse viruses with multiple gene constellations were isolated from both winter and summer, with a total of 19 distinct genotypes identified. Comparative phylogenetic analysis of all eight segments of 40 virus isolates from summer and 122 isolates from winter revealed that the summer and winter isolates were genetically distinct, indicating IAVs are not maintained in the market, but rather are re‐introduced, likely from commercial swine. These findings highlight the extent of IAV genetic diversity circulating in swine in live animal markets, even during summer months, and the ongoing risk to humans. [ABSTRACT FROM AUTHOR]

Rationale: The urinary proteome reflects molecular drivers of disease.Objectives: To construct a urinary proteomic biomarker predicting 1-year post-ICU mortality.Methods: In 1243 patients, the urinary proteome was measured on ICU admission, using capillary electrophoresis coupled with mass spectrometry along with clinical variables, circulating biomarkers (BNP, hsTnT, active ADM, and NGAL), and urinary albumin. Methods included support vector modeling to construct the classifier, Cox regression, the integrated discrimination (IDI), and net reclassification (NRI) improvement, and area under the curve (AUC) to assess predictive accuracy, and Proteasix and protein-proteome interactome analyses.Measurements and Main Results: In the discovery (deaths/survivors, 70/299) and test (175/699) datasets, the new classifier ACM128, mainly consisting of collagen fragments, yielding AUCs of 0.755 (95% CI, 0.708-0.798) and 0.688 (0.656-0.719), respectively. While accounting for study site and clinical risk factors, hazard ratios in 1243 patients were 2.41 (2.00-2.91) for ACM128 (+ 1 SD), 1.24 (1.16-1.32) for the Charlson Comorbidity Index (+ 1 point), and ≥ 1.19 (P ≤ 0.022) for other biomarkers (+ 1 SD). ACM128 improved (P ≤ 0.0001) IDI (≥ + 0.50), NRI (≥ + 53.7), and AUC (≥ + 0.037) over and beyond clinical risk indicators and other biomarkers. Interactome mapping, using parental proteins derived from sequenced peptides included in ACM128 and in silico predicted proteases, including/excluding urinary collagen fragments (63/35 peptides), revealed as top molecular pathways protein digestion and absorption, lysosomal activity, and apoptosis.Conclusions: The urinary proteomic classifier ACM128 predicts the 1-year post-ICU mortality over and beyond clinical risk factors and other biomarkers and revealed molecular pathways potentially contributing to a fatal outcome. [ABSTRACT FROM AUTHOR]

In Answer to Job, Jung quotes Tertullian from his De Testimonio Animae: "What you allow to the mistress you will assign to the disciples." Nature is the mistress and we are all potential disciples. If we look carefully and sympathetically at nature, we see that she is a process with one main overlying meta-pattern. All stable patterns in nature contain a balance of forces, a kind of reconciliation of opposites. This is true from the formation of hydrogen soon after the Big Bang, through the process of star formation and in the biological functions of living systems. One of the more beautiful ways to understand this concept of dinergy is to look at the pattern formations on the surface of seashells. Just as the telescope has enabled us to understand the process and pattern of planetary motions, so has the computer enabled a better understanding of weather patterns and the patterning on seashells. Although the neo-Darwinists would have us believe that such intricate and beautiful designs must have some survival benefit, I think that the deeper insight into nature comes from Thomas Mann (1947/1999) in his novel Doctor Faustus, in which he wrote that "meaning and design always run alongside one another" (p. v). These patterns are a manifestation of process and emergence. But most importantly, these patterns represent an essential feature in all dynamic systems: that is, a positive feedback that self-enhances the initial deviation from the mean. However, sooner or later, self-enhancing processes evoke antagonistic (opposing) reactions. Of course, Jung understood this long before systems theory, as enantiodromia. [ABSTRACT FROM AUTHOR]

This paper examines the meaning of plurality and diversity with respect to deaf children's sign and spoken language exposure and repertoire within a super diverse context. Data is drawn from a small-scale project that took place in the North of England in a Local Authority (LA) site for deaf education. The project documented the language landscape of this site and gathered five individual case studies of deaf children to examine their plural and diverse language practices at home and at school. Analysis of the language landscape and case studies from this context is undertaken in order to define and exemplify deaf children's language plurality and diversity in terms of context and individual experience. Concepts of repertoire are explored with particular reference to the unique type of translanguaging that the plural use of sign and spoken languages affords. Implications of these preliminary insights are discussed in terms of the development of methodologies that are sensitive to the particular translanguaging practices of deaf children, and approaches to pedagogy that are appropriately nuanced and responsive to deaf children's language plurality and diversity. [ABSTRACT FROM AUTHOR]