Search

The regulation and recruitment of γ-TuRCs, the prime nucleator of microtubules, to the centrosome are still thrust areas of research. The interaction of fodrin, a sub-plasmalemmal cytoskeletal protein, with γ-tubulin is a new area of interest. To understand the cellular significance of this interaction, we show that depletion of α-fodrin brings in a significant reduction of γ-tubulin in neural cell centrosomes making it functionally under-efficient. This causes a loss of nucleation ability that cannot efficiently form microtubules in interphase cells and astral microtubules in mitosis. Fluorescence Recovery after Photobleaching (FRAP) experiment implies that α-fodrin is important in the recruitment of γ-tubulin to the centrosome resulting in the aforementioned effects. Further, our experiments indicate that the interaction of α-fodrin with certain pericentriolar matrix proteins such as Pericentrin and CDK5RAP2 are crucial for the recruitment of γ-tubulin to the centrosome. Earlier we reported that α-fodrin limits the nucleation potential of γ-TuRC. In that context, this study suggests that α-fodrin is a γ-tubulin recruiting protein to the centrosome thus preventing cytoplasmic microtubule nucleation and thereby compartmentalizing the process to the centrosome for maximum efficiency.

Mrunal Vitthal Wanjale,1,2 Vishnu Sunil Jaikumar,3 KC Sivakumar,4 Riya Ann Paul,2,5 Jackson James,5 GS Vinod Kumar1 1Nano Drug Delivery Systems (NDDS), Cancer Biology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Thiruvananthapuram, Kerala, 695014, India; 2Research Scholar, Department of Biotechnology, Faculty of Applied Sciences & Technology, University of Kerala, Thiruvananthapuram, Kerala, 695581, India; 3Animal Research Facility, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Thiruvananthapuram, Kerala, 695014, India; 4Distributed Information Sub-Centre (Bioinformatics Centre), Bio-Innovation Center (BIC), Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram, Kerala, 695014, India; 5Neuro-Stem Cell Biology Lab, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Thiruvananthapuram, Kerala, 695014, IndiaCorrespondence: GS Vinod Kumar, Tel +91 471 2781217, Fax +91 471 2348096, Email gsvinod@rgcb.res.inPurpose: The brain, protected by the cranium externally and the blood–brain barrier (BBB) internally, poses challenges in chemotherapy of aggressive brain tumors. Maximal tumor resection followed by radiation and chemotherapy is the standard treatment protocol; however, a substantial number of patients suffer from recurrence. Systemic circulation of drugs causes myelodysplasia and other side effects. To address these caveats, we report facile synthesis of a polyester-based supramolecular hydrogel as a brain biocompatible implant for in situ delivery of hydrophobic drugs.Methods: Polycaprolactone-diol (PCL) was linked to polyethyleneglycol-diacid (PEG) via an ester bond. In silico modeling indicated micelle-based aggregation of PCL-PEG co-polymer to form a supramolecular hydrogel. Brain biocompatibility was checked in Sprague Dawley rat brain cortex with MRI, motor function test, and histology. Model hydrophobic drugs carmustine and curcumin entrapment propelled glioma cells into apoptosis-based death evaluated by in vitro cytotoxicity assays and Western blot. In vivo post-surgical xenograft glioma model was developed in NOD-SCID mice and evaluated for efficacy to restrict aggressive regrowth of tumors.Results: 20% (w/v) PCL-PEG forms a soft hydrogel that can cover the uneven and large surface area of a tumor resection cavity and maintain brain density. The PCL-PEG hydrogel was biocompatible, and well-tolerated upon implantation in rat brain cortex, for a study period of 12 weeks. We report for the first time the combination of carmustine and curcumin entrapped as model hydrophobic drugs, increasing their bioavailability and yielding synergistic apoptotic effect on glioma cells. Further in vivo study indicated PCL-PEG hydrogel with a dual cargo of carmustine and curcumin restricted aggressive regrowth post-resection significantly compared with control and animals with intravenous drug treatment.Conclusion: PCL-PEG soft gel-based implant is malleable compared with rigid wafers used as implants, thus providing larger surface area contact. This stable, biocompatible, supramolecular gel without external crosslinking can find wide applications by interchanging formulation of various hydrophobic drugs to ensure and increase site-specific delivery, avoiding systemic circulation.Graphical Abstract: Keywords: glioma, drug, delivery, brain, tumor, implant, surgery, hydrogel

Additional file 1. Supplemental Appendix.

The initial conditions found in infrared dark clouds (IRDCs) provide insights on how high-mass stars and stellar clusters form. We have conducted high-angular resolution and high-sensitivity observations toward thirty-nine massive IRDC clumps, which have been mosaicked using the 12m and 7m arrays from the Atacama Large Millimeter/submillimeter Array (ALMA). The targets are 70 $μ$m dark massive (220-4900 $M_\odot$), dense ($>$10$^4$ cm$^{-3}$), and cold ($\sim$10-20K) clumps located at distances between 2 and 6 kpc. We identify an unprecedented number of 839 cores, with masses between 0.05 and 81 $M_\odot$ using 1.3 mm dust continuum emission. About 55% of the cores are low-mass ($, Accepted for Publication in ApJ. 54 pages, 40 figures, 5 tables

Our capacity to process large complex data sources is ever-increasing, providing us with new, important applied research questions to address, such as how to handle missing values in large-scale databases. Mitra et al. (2023) noted the phenomenon of Structured Missingness (SM), which is where missingness has an underlying structure. Existing taxonomies for defining missingness mechanisms typically assume that variables' missingness indicator vectors $M_1$, $M_2$, ..., $M_p$ are independent after conditioning on the relevant portion of the data matrix $\mathbf{X}$. As this is often unsuitable for characterising SM in multivariate settings, we introduce a taxonomy for SM, where each ${M}_j$ can depend on $\mathbf{M}_{-j}$ (i.e., all missingness indicator vectors except ${M}_j$), in addition to $\mathbf{X}$. We embed this new framework within the well-established decomposition of mechanisms into MCAR, MAR, and MNAR (Rubin, 1976), allowing us to recast mechanisms into a broader setting, where we can consider the combined effect of $\mathbf{X}$ and $\mathbf{M}_{-j}$ on ${M}_j$. We also demonstrate, via simulations, the impact of SM on inference and prediction, and consider contextual instances of SM arising in a de-identified nationwide (US-based) clinico-genomic database (CGDB). We hope to stimulate interest in SM, and encourage timely research into this phenomenon.

ObjectivesSocial determinants of health (SDoH) contribute to health outcomes. We identified SDoH that were modified by critical illness, and the effect of such modifications on recovery from critical illness.DesignIn-depth semistructured interviews following hospital discharge. Interview transcripts were mapped against a pre-existing social policy framework: money and work; skills and education; housing, transport and neighbourhoods; and family, friends and social connections.Setting14 hospital sites in the USA, UK and Australia.ParticipantsPatients and caregivers, who had been admitted to critical care from three continents.Results86 interviews were analysed (66 patients and 20 caregivers). SDoH, both financial and non-financial in nature, could be negatively influenced by exposure to critical illness, with a direct impact on health-related outcomes at an individual level. Financial modifications included changes to employment status due to critical illness-related disability, alongside changes to income and insurance status. Negative health impacts included the inability to access essential healthcare and an increase in mental health problems.ConclusionsCritical illness appears to modify SDoH for survivors and their family members, potentially impacting recovery and health. Our findings suggest that increased attention to issues such as one’s social network, economic security and access to healthcare is required following discharge from critical care.

Until recently, multiple synthetic data sets were always released to analysts, to allow valid inferences to be obtained. However, under certain conditions - including when saturated count models are used to synthesize categorical data - single imputation ($m=1$) is sufficient. Nevertheless, increasing $m$ causes utility to improve, but at the expense of higher risk, an example of the risk-utility trade-off. The question, therefore, is: which value of $m$ is optimal with respect to the risk-utility trade-off? Moreover, the paper considers two ways of analysing categorical data sets: as they have a contingency table representation, multiple categorical data sets can be averaged before being analysed, as opposed to the usual way of averaging post-analysis. This paper also introduces a pair of metrics, $\tau_3(k,d)$ and $\tau_4(k,d)$, that are suited for assessing disclosure risk in multiple categorical synthetic data sets. Finally, the synthesis methods are demonstrated empirically.

Intra-retinal axon guidance involves a coordinated expression of transcription factors, axon guidance genes, and secretory molecules within the retina. Pax6, the master regulator gene, has a spatio-temporal expression typically restricted till neurogenesis and fate-specification. However, our observation of persistent expression of Pax6 in mature RGCs led us to hypothesize that Pax6 could play a major role in axon guidance after fate specification. Here, we found significant alteration in intra-retinal axon guidance and fasciculation upon knocking out of Pax6 in E15.5 retina. Through unbiased transcriptome profiling between Pax6fl/fl and Pax6−/− retinas, we revealed the mechanistic insight of its role in axon guidance. Our results showed a significant increase in the expression of extracellular matrix molecules and decreased expression of retinal fate specification and neuron projection guidance molecules. Additionally, we found that EphB1 and Sema5B are directly regulated by Pax6 owing to the guidance defects and improper fasciculation of axons. We conclude that Pax6 expression post fate specification of RGCs is necessary for regulating the expression of axon guidance genes and most importantly for maintaining a conducive ECM through which the nascent axons get guided and fasciculate to reach the optic disc.

Wetlands are an important and endangered habitat in Europe, making fishponds valuable areas for biodiversity, especially for birds. Crna Mlaka fishponds are protected as an ornithological reserve and Ramsar site, but there are also two other carp-producing fishponds in the same Special Protection Area Pokupski bazen (Draganić and Pisarovina), which are not as recognized. As part of a national monitoring project, these three fishponds were monitored almost every month during a one-year period. This research aims to show the yearly dynamic of birds at these sites (wintering, breeding, and migrating populations) but also to define through comparison which features of habitats, management practices or recorded threats and pressures impact species diversity and population sizes. We recorded 92 species in total, with over 13000 individuals in one month. While all fishponds showed high biodiversity and many interesting records, Draganić stands out as having the highest number of individual birds per month in most months. Reasons for this may relate to differences in water level management, causing high quality habitat types such as bare mud to be available during key periods. We can conclude that Draganić is as relevant for birds as the more protected Crna Mlaka and should be considered for further protection. This research also consolidates that fishponds are essential for many bird species year-round and the co-existence of birds and humans should be nurtured in these areas.

The increasing prevalence of non-communicable diseases remains an important source of concern in the Caribbean and Latin American regions. This study examines rates and the associated socio- demographic correlates of physical health indicators in Jamaica and Guyana. Area probability cross- sectional data were collected on 1,218 Jamaicans and 2,068 Guyanese participants in 2005. Physician- diagnosed hypertension, diabetes mellitus, arthritis, and self-rated oral and general physical health were assessed using descriptive statistics, chi-square, and hierarchical logistic regression analytic procedures. Jamaicans generally reported poorer physical health, including diabetes mellitus, arthritis, and overall perceived oral and physical health compared to Guyanese; Guyanese reported higher rates of hypertension. Generally, lower social and economic standing was associated with poorer health conditions but made different contributions across countries. The study highlights the need for greater awareness and access to health care services for individuals who are especially vulnerable to poorer health. The results of this study suggest the need for additional studies on factors associated with physical health conditions, including a better understanding of the role of race/ethnicity in the Caribbean.

Additional file 1: Online supplemental materials.

Additional file 1.

Ao tomar para título deste artigo a expressão clássica de um, dentre os vários textos de Jacques Le Goff que balizam as pesquisas dos historiadores da educação, buscamos evidenciar as questões que nos preocupam sobremaneira para tratar do temário no qual esse artigo se inscreve: Ensino de História e reflexões sobre história regional. Desta feita, nossa proposta de contribuição para os diálogos refere-se aos usos e formas de abordagem para a escrita da história e da história da educação, mediada por seus lugares de produção, circulação e contribuição para a consolidação ou silenciamento de uma Memória acerca das tradições educacionais (POLLACK, 1989, 1992), que se inscreve em alguns momentos, como forma legitimada e legitimadora de poder, conforme sinalizam os estudos de Pierre Bourdieu acerca da publicização do conhecimento, como formas de burlar o silêncio, de colocar assuntos e interesses em evidência. (BOURDIEU, 2005). Resultaram da pesquisa nos acervos, elementos que sustentam a contestação de alguns aspectos postulados por estudos em Mato Grosso e Mato Grosso do Sul, bem como indicativos de que há ainda muito por se escrever, em se tratando da história da educação deste Estado.

While the French Revolution brought about the end of Versailles as an active seat of politics and the Ancien Régime as a political and social system, both Versailles and the Ancien Régime remain important symbols of the past, and what Pierre Nora calls lieux de mémoire, in the cultural fabric French Republic, not least because they serve as a frame of reference for that paradox of continuity and disjuncture between ‘old’ and ‘modern’ France. With specific reference to film as a repository for historical memory, this thesis will examine the ways in which historical films that deal with Versailles and the monarchy (I will focus in depth on four case studies: La Marseillaise, 1938; L’affaire du collier de la reine, 1946; Si Versailles m’était conte, 1953, and La Prise de pouvoir par Louis XIV, 1966) use this specific aspect of the past to speak the concerns of the present moment, to provide a sense of historical continuity, to affirm a particular social contract based upon a set of national traditions, or to bind the various traditions of France’s past together into a common or shared culture predicated upon the existence of a national heritage. Ultimately, this thesis argues that Versailles and the Ancien Régime (as symbols, metonyms, epochs) hold such cultural, historical, and political weight that their memory is firmly embedded within French culture and regardless of their idiosyncrasies, differing tones, textures, and political or artistic perspectives, the various films about them, including the films under discussion. Moreover, it maintains (with close reference to the films) that in addition to being conduits for memory, historical films hold the capacity for doing History (with a capital ‘H’).

Objectives: \ud To understand the unmet needs of caregivers of ICU survivors, how they accessed support post ICU, and the key components of beneficial ICU recovery support systems as identified from a caregiver perspective.\ud \ud Design: \ud International, qualitative study.\ud \ud Subjects: \ud We conducted 20 semistructured interviews with a diverse group of caregivers in the United States, the United Kingdom, and Australia, 11 of whom had interacted with an ICU recovery program.\ud \ud Setting: \ud Seven hospitals in the United States, United Kingdom, and Australia.\ud \ud Interventions: \ud None.\ud \ud Measurements and Main Results: \ud Content analysis was used to explore prevalent themes related to unmet needs, as well as perceived strategies to improve ICU outcomes. Post-ICU care was perceived to be generally inadequate. Desired caregiver support fell into two main categories: practical support and emotional support. Successful care delivery initiatives included structured programs, such as post discharge telephone calls, home health programs, post-ICU clinics, and peer support groups, and standing information resources, such as written educational materials and online resources.\ud \ud Conclusions: \ud This qualitative, multicenter, international study of caregivers of critical illness survivors identified consistently unmet needs, means by which caregivers accessed support post ICU, and several care mechanisms identified by caregivers as supporting optimal ICU recovery.

A pesquisa histórica em Educação revela faces dos processos de apropriação cultural significativos para compreensão tanto de aspectos sociais, bem como as distinções/preconceitos que por muitas vezes o cotidiano escolar teima em silenciar, a exemplo do que pontua Candau (2011). Nesse sentido, o presente trabalho objetiva colocar em evidência os resultados de pesquisa aplicada na comunidade escolar da periferia da cidade de Dourados, Mato Grosso do Sul, no que concerne a uma particularidade observada durante projetos de ensino e pesquisa desenvolvidos naquela instituição, a saber, o índice significativo de crianças que descendem em primeira ou segunda geração de famílias que imigraram do Paraguai para Dourados, entre as décadas de 1960 a 1980. Tal dado foi objetivado a partir de pesquisa qualitativa aplicada na Escola, com vistas à obtenção de um quadro geral da comunidade escolar para vislumbrar a aplicação de projetos em turmas de Ensino Fundamental Anos Finais. Os dados surpreenderam a todos os envolvidos, pois muito embora houvesse suspeitas a respeito, não havia mecanismos efetivos de comprovação da hipótese, para além da observação da compleição física e características gerais, identificadas nos sobrenomes das crianças matriculadas. Revelaram, ainda, que muitas dessas crianças não conhecem a história de sua origem, facultando à escola possibilidades variadas de trabalho pedagógico, tanto de ordem histórica, como em outras áreas do conhecimento escolar.

Background:\ud After critical illness, patients are often left with impairments in physical, social, emotional, and cognitive functioning. Peer support interventions have been implemented internationally to ameliorate these issues.\ud \ud Objective:\ud To explore what patients believed to be the key mechanisms of effectiveness of peer support programs implemented during critical care recovery.\ud \ud Methods:\ud In a secondary analysis of an international qualitative data set, 66 telephone interviews with patients were undertaken across 14 sites in Australia, the United Kingdom, and the United States to understand the effect of peer support during recovery from critical illness. Prevalent themes were documented with framework analysis.\ud \ud Results:\ud Most patients who had been involved in peer support programs reported benefit. Patients described 3 primary mechanisms: (1) sharing experiences, (2) care debriefing, and (3) altruism.\ud \ud Conclusion:\ud Peer support is a relatively simple intervention that could be implemented to support patients during recovery from critical illness. However, more research is required into how these programs can be implemented in a safe and sustainable way in clinical practice.

Radiation treatment for tongue and throat cancer causes side effects. These side effects make it hard for patients to eat and they sometimes feeding needs tubes put directly into their stomach, so food can be put directly in. This thesis aims to identify patients who may need feeding tubes and looks for ways to minimise this need. It also examines patients acceptance of feeding tubes.

Over the past three decades, synthetic data methods for statistical disclosure control have continually evolved, but mainly within the domain of survey data sets. There are certain characteristics of administrative databases, such as their size, which present challenges from a synthesis perspective and require special attention. This paper, through the fitting of saturated count models, presents a synthesis method that is suitable for administrative databases that is tuned by two parameters. The method allows large categorical data sets to be synthesized quickly and allows risk and utility metrics to be satisfied a priori, that is, prior to synthetic data generation. The paper explores how the flexibility afforded by two-parameter count models (the negative binomial and Poisson-inverse Gaussian) can be utilised to protect respondents' - especially uniques' - privacy in synthetic data. Finally, an empirical example is carried out through the synthesis of a database which can be viewed as a good substitute to the English School Census., Comment: 37 pages, 6 figures

Anonymised interviews with five educational psychologists (EPs) have been transcribed verbatim. The researchers aimed to capture how participants expressed themselves, as well as what they said, to provide context around dialogue. Transcripts were occasionally altered to protect anonymity, in cases where participants described distinguishing features such as names and places. Here, care was taken to avoid altering meanings, maintaining an ethical balance of anonymity and authenticity (Poland, 2002). The five participants were selected based on their range of backgrounds, covering four local authorities in the north of England and three training courses from across the country. Three participants were EPs and two were senior EPs, with years of practice ranging from three to 35 years. Participants undertook an individual, semi-structured interview lasting one hour. Informed by Bronfenbrenner (2006), open-ended questions prompted reflection on how nested contextual layers shape the practice of individual EPs. Interview themes (values; the role of others; success and challenge; change and stability; training and policy) supported conversations, though structure and focus were responsive to the participant. Ethical approval was granted by the Social and Health Sciences Ethics Committee, Leeds Trinity University (UK), and in line with the code of conduct of the British Psychological Society. Participants were made aware of the voluntary nature of their involvement, their right to stop or pause at any point during the interview or withdraw from the study up to ten working days following data collection. Participants (and others mentioned during the interview) have been anonymised.

We present a spatio-kinematical analysis of the CO~($J$=2$\rightarrow$1) line emission, observed with the Atacama Large Millimter/submillimter Array (ALMA), of the outflow associated with the most massive core, ALMA1, in the 70 $��$m dark clump G010.991$-$00.082. The position-velocity (P-V) diagram of the molecular outflow exhibits a peculiar $\mathsf{S}$-shaped morphology that has not been seen in any other star forming region. We propose a spatio-kinematical model for the bipolar molecular outflow that consists of a decelerating high-velocity component surrounded by a slower component whose velocity increases with distance from the central source. The physical interpretation of the model is in terms of a jet that decelerates as it entrains material from the ambient medium, which has been predicted by calculations and numerical simulations of molecular outflows in the past. One side of the outflow is shorter and shows a stronger deceleration, suggesting that the medium through which the jet moves is significantly inhomogeneous. The age of the outflow is estimated to be $��$$\approx$1300 years, after correction for a mean inclination of the system of $\approx$57$^{\circ}$., 15 pages, 7 figures. Accepted for publication in ApJ

Background Advances in critical care medicine have led to a growing number of critical illness survivors. A considerable part of them suffers from long-term sequelae, also known as post-intensive care syndrome. Among these, depressive symptoms are frequently observed. Depressive symptom trajectories and associated factors of critical illness survivors have rarely been investigated. Study objective was to explore and compare different trajectories of depressive symptoms in sepsis survivors over 1 year after discharge from ICU. Methods Data of a randomized controlled trial on long-term post-sepsis care were analyzed post hoc. Depressive symptoms were collected at 1, 6 and 12 months post-ICU discharge using the Major Depression Inventory (MDI), among others. Statistical analyses comprised descriptive analysis, univariate and multivariate, linear and logistic regression models and Growth Mixture Modeling. Results A total of 224 patients were included into this analysis. We identified three latent classes of depressive symptom trajectories: Over the course of 1 year, 152 patients recovered from mild symptoms, 27 patients showed severe persistent symptoms, and 45 patients recovered from severe symptoms. MDI sum scores significantly differed between the three classes of depressive symptom trajectories at 1 and 6 months after ICU discharge (p

BackgroundCOVID-19 curve can be flattened by adopting mass screening protocols with aggressive testing and isolating infected populations. The current approach largely depends on RT-PCR/rapid antigen tests that require expert personnel resulting in higher costs and reduced testing frequency. Loss of smell is reported as a major symptom of COVID-19, however, a precise olfactory testing tool to identify COVID-19 patient is still lacking.MethodsTo quantitatively check for the loss of smell, we developed an odor strip, “COVID-Anosmia checker”, spotted with gradients of coffee and lemon grass oil. We validated its efficiency in healthy and COVID-19 positive subjects. A trial screening to identify SARS-CoV-2 infected persons was also carried out to check the sensitivity and specificity of our screening tool.FindingsIt was observed that COVID positive participants were hyposmic instead of being anosmic when they were subjected to smelling higher odor concentration. Our tool identified 97% of symptomatic and 94% of asymptomatic COVID-19 positive subjects after excluding most confounding factors like concurrent chronic sinusitis. Further, it was possible to reliably predict COVID-19 infection by calculating a loss of smell score with 100% specificity. We coupled this tool with a mobile application, which takes the input response from the user, and can readily categorize the user in the appropriate risk groups.ConclusionLoss of smell can be used as a reliable marker for screening for COVID-19. Our tool can be used for first-line screening to trace out COVID-19 infection effectively. It can be used in difficult to reach geographical locations.

Background: \ud After critical illness, new or worsening impairments in physical, cognitive, and/or mental health function are common among patients who have survived. Who should be screened for long-term impairments, what tools to use, and when remain unclear.\ud \ud Objectives: \ud Provide pragmatic recommendations to clinicians caring for adult survivors of critical illness related to screening for postdischarge impairments.\ud \ud Participants: \ud Thirty-one international experts in risk-stratification and assessment of survivors of critical illness, including practitioners involved in the Society of Critical Care Medicine’s Thrive Post-ICU Collaboratives, survivors of critical illness, and clinical researchers.\ud \ud Design: \ud Society of Critical Care Medicine consensus conference on post-intensive care syndrome prediction and assessment, held in Dallas, in May 2019. A systematic search of PubMed and the Cochrane Library was conducted in 2018 and updated in 2019 to complete an original systematic review and to identify pre-existing systematic reviews.\ud \ud Meeting Outcomes: \ud We concluded that existing tools are insufficient to reliably predict post-intensive care syndrome. We identified factors before (e.g., frailty, preexisting functional impairments), during (e.g., duration of delirium, sepsis, acute respiratory distress syndrome), and after (e.g., early symptoms of anxiety, depression, or post-traumatic stress disorder) critical illness that can be used to identify patients at high-risk for cognitive, mental health, and physical impairments after critical illness in whom screening is recommended. We recommend serial assessments, beginning within 2–4 weeks of hospital discharge, using the following screening tools: Montreal Cognitive Assessment test; Hospital Anxiety and Depression Scale; Impact of Event Scale-Revised (post-traumatic stress disorder); 6-minute walk; and/or the EuroQol-5D-5L, a health-related quality of life measure (physical function).\ud \ud Conclusions: \ud Beginning with an assessment of a patient’s pre-ICU functional abilities at ICU admission, clinicians have a care coordination strategy to identify and manage impairments across the continuum. As hospital discharge approaches, clinicians should use brief, standardized assessments and compare these results to patient’s pre-ICU functional abilities (“functional reconciliation”). We recommend serial assessments for post-intensive care syndrome-related problems continue within 2–4 weeks of hospital discharge, be prioritized among high-risk patients, using the identified screening tools to prompt referrals for services and/or more detailed assessments.

Objectives: \ud \ud To understand from the perspective of patients who did, and did not attend ICU recovery programs, what were the most important components of successful programs and how should they be organized.\ud \ud Design: \ud \ud International, qualitative study.\ud \ud Setting: \ud \ud Fourteen hospitals in the United States, United Kingdom, and Australia.\ud Patients: \ud \ud We conducted 66 semi-structured interviews with a diverse group of patients, 52 of whom had used an ICU recovery program and 14 whom had not.\ud \ud Interventions: \ud \ud None.\ud \ud Measurements and Main Results: \ud \ud Using content analysis, prevalent themes were documented to understand what improved their outcomes. Contrasting quotes from patients who had not received certain aspects of care were used to identify perceived differential effectiveness. Successful ICU recovery programs had five key components: 1) Continuity of care; 2) Improving symptom status; 3) Normalization and expectation management; 4) Internal and external validation of progress; and 5) Reducing feelings of guilt and helplessness. The delivery of care which achieved these goals was facilitated by early involvement (even before hospital discharge), direct involvement of ICU staff, and a focus on integration across traditional disease, symptom, and social welfare needs.\ud \ud Conclusions: \ud \ud In this multicenter study, conducted across three continents, patients identified specific and reproducible modes of benefit derived from ICU recovery programs, which could be the target of future intervention refinement.

Efficacy ofBovi-Shield GOLD® FP® 5 VL5 in heifers at five to seven months of gestation was evaluated following exposure to seeder calves persistently infected (Pl) with bovine viral diarrhea virus (BVDV) type 2., American Association of Bovine Practitioners Proceedings of the Annual Conference, 2006

Additional file 1: Table 1. Most frequently reported cardiovascular conditions experienced by patients according to response to triptan medication (physician-reported). Table 2. Summary of patient-reported outcomes in patients with migraine receiving treatment for acute migraine: unadjusted results. Table 3. Summary of patient-reported outcomes in patients with migraine receiving treatment for acute migraine; multivariate analysis controlling for age, gender, migraine headache day frequency, comorbidities, duration of illness, preventive medication use, with or without aura.

Additional file 1 : Table S1. Current migraine-related symptom severity by response to acute treatment for migraine.

Additional file 2. Table 2 KDQOL-36, SF-12 PCS and MCS scores by geographical region, Hb level and CKD stage.

Supplemental material, SALSA_Stress_JAH_Supplemental_Tables_2019-04-11 for Allostatic Load, Unhealthy Behaviors, and Depressive Symptoms by Birthplace Among Older Adults in the Sacramento Area Latino Study on Aging (SALSA) by Erik J. Rodriquez, Melanie Sabado-Liwag, Eliseo J. Pérez-Stable, Anne Lee, Mary N. Haan, Steven E. Gregorich, James S. Jackson and Anna M. Nápoles in Journal of Aging and Health

We present a study of outflows at extremely early stages of high-mass star formation obtained from the ALMA Survey of 70 $��\rm m$ dark High-mass clumps in Early Stages (ASHES). Twelve massive 3.6$-$70 $��\rm m$ dark prestellar clump candidates were observed with the Atacama Large Millimeter/submillimeter Array (ALMA) in Band 6. Forty-three outflows are identified toward 41 out of 301 dense cores using the CO and SiO emission lines, yielding a detection rate of 14%. We discover 6 episodic molecular outflows associated with low- to high-mass cores, indicating that episodic outflows (and therefore episodic accretion) begin at extremely early stages of protostellar evolution for a range of core masses. The time span between consecutive ejection events is much smaller than those found in more evolved stages, which indicates that the ejection episodicity timescale is likely not constant over time. The estimated outflow dynamical timescale appears to increase with core masses, which likely indicates that more massive cores have longer accretion timescales than less massive cores. The lower accretion rates in these 70 $��\rm m$ dark objects compared to the more evolved protostars indicate that the accretion rates increase with time. The total outflow energy rate is smaller than the turbulent energy dissipation rate, which suggests that outflow induced turbulence cannot sustain the internal clump turbulence at the current epoch. We often detect thermal SiO emission within these 70 $��\rm m$ dark clumps that is unrelated to CO outflows. This SiO emission could be produced by collisions, intersection flows, undetected protostars, or other motions., 32 pages, 9 figures, 4 tables, accepted for publication in ApJ

Supplemental material, sj-pdf-1-eeg-10.1177_1550059420978009 for Quantitative EEG During Critical Illness Correlates With Patterns of Long-Term Cognitive Impairment by Shawniqua Williams Roberson, Naureen Abdul Azeez, Randip Taneja, Brenda T. Pun, Pratik P. Pandharipande, James C. Jackson and E. Wesley Ely in Clinical EEG and Neuroscience

Additional file 2 : Figure S1. Change in level of impairment over past 6 months by response to acute treatment for migraine.

Additional file 1. Table 1 EQ-5D-3 L utility index and VAS scores by geographical region, Hb level and CKD stage.

Additional file 3 Fig. 1 The three main phases of a Disease Specific Programme (DSP). Figure 2 Distribution of current Hb levels.

A glycopeptide bearing a bisecting glucosamine, a rare N-glycan branch, and two LewisX trisaccharides was synthesized for the first time., N-Linked glycopeptides have highly diverse structures in nature. Herein, we describe the first synthesis of rare multi-antennary N-glycan bearing glycan chains on 6-OH of both α1,6- and α1,3-linked mannose arms. To expedite divergent generation of N-glycan structures, four orthogonal protective groups were installed at the branching points on the core tetrasaccharide, which could be removed individually without affecting one another. In addition, the synthetic route is flexible, allowing a bisecting glucosamine moiety to be introduced at a late stage of the synthesis, further expanding the diversity of sequences that could be achieved. The bisecting glucosamine unit significantly reduced the glycosylation yields of adjacent mannoses, which was attributed to steric hindrance imposed by the glucosamine based on molecular modelling analysis. The N-glycans were then transformed to oxazoline donors and ligated with a glycopeptide acceptor from haptoglobin promoted by the wild type Arthrobacter endo-β-N-acetylglucosaminidase (Endo-A). Endo-A exhibited interesting substrate preferences depending on donor sizes, which was rationalized through molecular dynamics studies. This is the first time that a glycopeptide bearing a bisecting N-acetyl glucosamine (GlcNAc), the rare N-glycan branch, and two LewisX trisaccharide antennae was synthesized, enabling access to this class of complex glycopeptide structures.

For four related 1,1-disubstituted olefins, (DHQD)2PHAL-catalyzed asymmetric chlorocyclization delivers Cl+ uniformly to one π face, but cyclizes with strong but differing net syn vs. anti addition., Though (DHQD)2PHAL-catalyzed chlorocyclizations of 1,1-disubstituted olefins show useful (and in some cases, reversible) asymmetric induction, stereochemically complete descriptions of these alkene additions have remained largely unknown. Herein, based on a combination of NMR, derivative, isotope labeling, and computational studies, we present detailed stereochemical analyses of chlorocyclizations of nucleophile-tethered 1,1-disubstituted styryl systems. The selectivities of the two asymmetric bond-forming processes, namely electrophilic chlorine attack and nucleophilic ring closure, are thus mapped out independently. Under the established optimal conditions, four related chlorocyclizations were subjected to this analysis. All showed a strong preference for Cl+ delivery from the same face of the alkene. However, depending on reaction conditions and substrate identity (carboxylic acid, amide or carbamate), the internal nucleophiles may close with a strong net preference for either syn or anti addition relative to the Cl atom. Studies of both uncatalyzed and (DHQD)2PHAL-catalyzed processes place new boundary conditions on the role of the catalyst in these reactions.

O presente trabalho tem como objetivo apresentar a análise de livros didáticos de História do Ensino Fundamental – Anos Finais – no que concerne à observância de recorrência de textos permeados por uma escrita subalternizante sobre os Povos Indígenas brasileiros. Desse modo, com base em estudos que discutem os conceitos de colonização, descolonização e subalternidade (HENRIQUES 2015, MEMMI 1997, SANTOS 2007), na literatura ligada aos estudos sobre livro didáticos de história no Brasil e em Mato Grosso do Sul (DEBONA, 2015) e legislação educacional brasileira (Lei 11.645/2008, Art. 26-A), procedemos a seleção e análise de duas coleções de livros didáticos aprovadas no Programa Nacional do Livro Didático, triênio de 2011, que circularam pelas escolas estaduais de Mato Grosso do Sul do Ensino Fundamental - Séries Finais: Projeto Araribá História e a coleção História sociedade & cidadania- nova edição. Foram analisados os exemplares que compõe a coleção, no esforço de mapear a recorrência do temário Povos Indígenas, observando suas formas de representação no conteúdo, o lugar que ocupam na história Nacional, registros de sua influência cultural e outros aspectos. Percebemos a ausência da abordagem a partir da cultura indígena, o que nega os como pertencentes à História da sociedade civil, apontando sua presença, mas não a efetivação de discussões sobre o tema no campo do ensino.

Table S1. Drug classes being taken for the treatment of comorbidities by â Ľ5% of patients with episodic and chronic migraine and any comorbidity: physician-reported data. (DOCX 15 kb)

As the every day use of mobile and small screen devices becomes more common, it is necessary to explore how we can visualise data effectively in small design spaces. These screens are often used in situations where it is necessary to convey information in a concise, readable, reliable and visually appealing way. Our work focuses on the design and development of a tool to facilitate the creation and manipulation of new micro-visualisations. The results show that the tool is suitable for creating large number of outputs quickly and efficiently., Computer Graphics and Visual Computing (CGVC), Short Papers, 141, 145, James Robert Jackson, Panagiotis D. Ritsos, and Jonathan C. Roberts, CCS Concepts: Human-centered computing --> Visualization

The AT1 receptor (AT1R) mediates the manifold actions of angiotensin II in the cardiovascular system. This study probed the molecular mechanisms that link altered redox status to AT1R expression in cardiac fibroblasts. Real-time PCR and western blot analysis showed that H2O2 enhances AT1R mRNA and protein expression via NADPH oxidase-dependent reactive oxygen species induction. Activation of NF-κB and AP-1, demonstrated by electrophoretic mobility shift assay, abolition of AT1R expression by their inhibitors, Bay-11-7085 and SR11302, respectively, and luciferase and chromatin immunoprecipitation assays confirmed transcriptional control of AT1R by NF-κB and AP-1 in H2O2-treated cells. Further, inhibition of ERK1/2, p38 MAPK and c-Jun N-terminal kinase (JNK) using chemical inhibitors or by RNA interference attenuated AT1R expression. Inhibition of the MAPKs showed that while ERK1/2 and p38 MAPK suffice for NF-κB activation, all three kinases are required for AP-1 activation. H2O2 also increased collagen type I mRNA and protein expression. Interestingly, the AT1R antagonist, candesartan, attenuated H2O2-stimulated AT1R and collagen mRNA and protein expression, suggesting that H2O2 up-regulates AT1R and collagen expression via local Angiotensin II generation, which was confirmed by real-time PCR and ELISA. To conclude, oxidative stress enhances AT1R gene expression in cardiac fibroblasts by a complex mechanism involving the redox-sensitive transcription factors NF-κB and AP-1 that are activated by the co-ordinated action of ERK1/2, p38 MAPK and JNK. Importantly, by causally linking oxidative stress to Angiotensin II and AT1R up-regulation in cardiac fibroblasts, this study offers a novel perspective on the pathogenesis of cardiovascular diseases associated with oxidative stress.

Delineation of mechanisms underlying the regulation of fibrosis-related genes in the heart is an important clinical goal as cardiac fibrosis is a major cause of myocardial dysfunction. This study probed the regulation of Discoidin Domain Receptor 2 (DDR2) gene expression and the regulatory links between Angiotensin II, DDR2 and collagen in Angiotensin II-stimulated cardiac fibroblasts. Real-time PCR and western blot analyses showed that Angiotensin II enhances DDR2 mRNA and protein expression in rat cardiac fibroblasts via NADPH oxidase-dependent reactive oxygen species induction. NF-κB activation, demonstrated by gel shift assay, abolition of DDR2 expression upon NF-κB inhibition, and luciferase and chromatin immunoprecipitation assays confirmed transcriptional control of DDR2 by NF-κB in Angiotensin II-treated cells. Inhibitors of Phospholipase C and Protein kinase C prevented Angiotensin II-dependent p38 MAPK phosphorylation that in turn blocked NF-κB activation. Angiotensin II also enhanced collagen gene expression. Importantly, the stimulatory effects of Angiotensin II on DDR2 and collagen were inter-dependent as siRNA-mediated silencing of one abolished the other. Angiotensin II promoted ERK1/2 phosphorylation whose inhibition attenuated Angiotensin II-stimulation of collagen but not DDR2. Furthermore, DDR2 knockdown prevented Angiotensin II-induced ERK1/2 phosphorylation, indicating that DDR2-dependent ERK1/2 activation enhances collagen expression in cells exposed to Angiotensin II. DDR2 knockdown was also associated with compromised wound healing response to Angiotensin II. To conclude, Angiotensin II promotes NF-κB activation that up-regulates DDR2 transcription. A reciprocal regulatory relationship between DDR2 and collagen, involving cross-talk between the GPCR and RTK pathways, is central to Angiotensin II-induced increase in collagen expression in cardiac fibroblasts.

The next-generation Very Large Array (ngVLA) is an astronomical observatory planned to operate at centimeter wavelengths (25 to 0.26 centimeters, corresponding to a frequency range extending from 1.2 to 116 GHz). The observatory will be a synthesis radio telescope constituted of approximately 244 reflector antennas each of 18 meters diameter, and 19 reflector antennas each of 6 meters diameter, operating in a phased or interferometric mode. We provide a technical overview of the Reference Design of the ngVLA. This Reference Design forms a baseline for a technical readiness assessment and the construction and operations cost estimate of the ngVLA. The concepts for major system elements such as the antenna, receiving electronics, and central signal processing are presented., To be published in the ASP Monograph Series, "Science with a Next-Generation VLA", ed. E. J. Murphy (ASP, San Francisco, CA). arXiv admin note: substantial text overlap with arXiv:1806.08405