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Young children from impoverished backgrounds experience high levels of family and environmental stress, adversely impacting developmental functioning. Early identification provides a pathway to solutions, but many children are never assessed. In addition, the child-serving workforce lacks resources and expertise to use traditional measures. Furthermore, existing measures do not account for the substantial influence of a child’s ecology. To bridge these gaps, we developed the Neurodevelopmental Ecological Screening Tool (NEST) and conducted a pilot study (n=60) to test its feasibility for use with caregivers of children ages 3-5 in low-resource settings. We developed an item pool across three domains (child, caregiver, environment), vetted it with experts, and conducted cognitive interviewing with parents (n=15) and case managers (n-10). Simultaneously, we built an online, user-friendly delivery platform. We used a one parameter Item Response Model and a Rasch-based Rating Scale Model (RSM) and fit confirmatory factor analytic (CFA) models to test for unidimensional and construct validity. The results support the feasibility of screening children from low SES populations within low-resource settings using an ecological perspective and supports the work of child-serving paraprofessionals in identifying and addressing risks in the lives of young children.

Effective surveillance of microbial communities in the healthcare environment is increasingly important in infection prevention. However, current workflows are insufficient for proper risk assessment. Upon evaluating and optimizing techniques, we recommend best practices and introduce a well-structured workflow for metagenomics-based environmental surveillance that is appropriate for low-biomass samples, distinguishes viability, and is quantitative. The workflow was developed using a representative microbiome sample, which was created by aggregating 120 surface swabs collected from a medical intensive care unit. We recommend liquid-liquid extraction, propidium monoazide treatment coupled with internal standards and absolute abundance profiling (e.g., using qPCR), and a machine learning-based model for sequencing depth calculation. In addition, whole-cell filtration and cultivation may be valuable under particular circumstances. This workflow will contribute to more accurate and robust environmental surveillance and infection prevention. Lessons gained from this study will also benefit the continuing development of methods in relevant fields.

Lens epithelium-derived growth factor splice variant of 75 kDa (LEDGF/p75) is an autoantigen over-expressed in solid tumors and acts as a stress-related transcriptional co-activator. Participation of autoimmune responses in the pathophysiology of benign prostatic hyperplasia (PBH) and a corresponding immunosuppressive therapy by TNFalpha antagonists has been recently suggested. Thus, autoAb testing could aid in the diagnosis of BPH patients profiting from such therapy. We generated CRISPR/Cas9 modified HEp-2 LEDGF knock-out (KO) and HEp-2 LEDGF/p75 over-expressing (OE) cells and examined IgG autoantibody reactivity to LEDGF/p75 in patients with prostate cancer (PCa, n = 89), bladder cancer (BCa, n = 116), benign prostatic hyperplasia (BPH, n = 103), and blood donors (BD, n = 60) by indirect immunofluorescence assay (IFA). Surprisingly, we could not detect elevated binding of autoAbs against LEDGF/p75 in cancer patients, but autoAb reactivity to LEDGF/p75 OE cells in about 50% of patients with BPH was unexpectedly significantly increased. Furthermore, a line immunoassay enabling the detection of 18 different autoAbs revealed a significantly increased occurrence of anti-dsDNA autoAbs in 34% of BPH patients in contrast to tumor patients and BD. This finding was confirmed by anti-mitochondrial (mDNA) autoAb detection with the Crithidia luciliae immunofluorescence test, which also showed a significantly higher prevalence (34%) of anti-mDNA autoAbs in BPH. In summary, our study provided further evidence for the occurrence of autoimmune responses in BPH. Furthermore, LEDGF/p75 over-expression renders HEp-2 cells more autoantigenic and an ideal target for autoAb analysis in BPH with a potential therapy consequence.

Spinal pain in adolescents is a significant public health concern, and adolescent sedentary behaviour is a proposed modifiable risk factor for spinal pain. Whether sedentary behaviour recommendations in international public health guidelines are relevant for adolescent spinal pain is unknown. This thesis reports a systematic review exploring associations between sedentary behaviours and spinal pain in adolescents. It also reports a secondary cross-sectional analysis, of a population-based cohort of young adolescent Danes, to investigate the association between sedentary behaviour (as per public health guidelines) and non-trivial spinal pain. Cross-sectional multinominal logistic regression investigated associations between sedentary behaviour, by duration and type, and spinal pain, by region and triviality, adjusted for age and sex. The systematic review found there was no meaningful association between sedentary behaviour and adolescent spinal pain; however, the evidence base is inconsistent and at high risk of bias. The cross-sectional analysis demonstrated there was no association between exceeding two hours per day of sedentary behaviour and spinal pain. The collective thesis findings suggest that sedentary behaviour is not a meaningful risk factor for adolescent back pain. Therefore, we challenge existing public and clinical beliefs that sedentary behaviour is causally associated with spinal pain in adolescents.

Unprecedented tree dieback across Central Europe caused by recent global change-type drought events highlights the need for a better mechanistic understanding of drought-induced tree mortality. Although numerous physiological risk factors have been identified, the importance of two principal mechanisms, hydraulic failure and carbon starvation, is still debated. It further remains largely unresolved how the local neighborhood composition affects individual mortality risk. We studied 9435 young trees of 12 temperate species planted in a diversity experiment in 2013 to assess how hydraulic traits, carbon dynamics, pest infestation, tree height and neighborhood competition influence individual mortality risk. Following the most extreme global change-type drought since record in 2018, one third of these trees died. Across species, hydraulic safety margins (HSMs) were negatively and a shift towards a higher sugar fraction in the non-structural carbohydrate (NSC) pool positively associated with mortality risk. Moreover, trees infested by bark beetles had a higher mortality risk, and taller trees a lower mortality risk. Most neighborhood interactions were beneficial, although neighborhood effects were highly species-specific. Species that suffered more from drought, especially Larix spp. and Betula spp., tended to increase the survival probability of their neighbors and vice versa. While severe tissue dehydration marks the final stage of drought-induced tree mortality, we show that hydraulic failure is interrelated with a series of other, mutually inclusive processes. These include shifts in NSC pools driven by osmotic adjustment and/or starch depletion as well as pest infestation and are modulated by the size and species identity of a tree and its neighbors. A more holistic view that accounts for multiple causes of drought-induced tree mortality is required to improve predictions of trends in global forest dynamics and to identify mutually beneficial species combinations.

Same-sex female couples who wish to become pregnant can choose donor insemination or in-vitro fertilization (IVF)—a technique intended for infertile women. In general, women in same-sex female partnerships are no more likely to be infertile than those in opposite sex partnerships. This article investigates data available from the Government Regulator of UK fertility clinics—the Human Fertilization and Embryology Authority, which is the only data available worldwide on same-sex female couples and their fertility choices. IVF is increasing both in absolute numbers and relative proportions year on year in the UK, compared to licensed donor insemination for same-sex female couples. As IVF has greater human and financial costs than donor insemination, policies should not encourage it as the first choice for fertile women requiring sperm. Commercial transactions are taking place where fertile lesbians receive cut price, and arguably unnecessary, IVF intervention in exchange for selling their eggs to be used for other infertile customers. If women are not told about the efficacy of fresh vs. frozen semen, and the risks of egg ‘sharing’ or intra-couple donation, exploitation becomes possible.

Narcolepsy type 1 (NT1) is a sleep–wake disorder caused by selective loss of hypocretin (HCRT, also called orexin) neurons. Although the prevalence of NT1 is equal in men and women, sex differences in NT1 symptomatology have been reported in humans and other species. Yet, most preclinical studies fail to include females, resulting in gender bias within translational drug development. We used hcrt-tTA;TetO DTA mice (NT1 mice) that lose their HCRT neurons upon dietary doxycycline removal to examine in detail the effect of sex on NT1 symptoms and sleep–wake characteristics. We recorded 24-h electroencephalography (EEG), electromyography (EMG), and video in adult male and female NT1 mice for behavioral state quantification. While conducting this study, we recognized another type of behavioral arrest different from cataplexy: shorter lasting and with high δ power. We termed these delta attacks and propose a set of criteria for quantifying these in future research. Our findings show that both sexes exhibit high behavioral state instability, which was markedly higher in females with more behavioral arrests interrupting the wake episodes. Females exhibited increased wake at the expense of sleep during the dark phase, and decreased rapid eye movement (REM) sleep during the 24-h day. During the dark phase, fast-δ (2.5–4 Hz) in non-rapid eye movement (NREM) sleep and θ (6–10 Hz) EEG spectral power in REM sleep were lower in females compared to males. We demonstrate that biologically driven sex-related differences exist in the symptomatology of NT1 mice which calls for including both sexes in future research.

Purpose Innovations in adolescent prevention and early intervention strategies are needed to curb early substance use and bring public health models to scale, such as Screening, Brief Intervention, and Referral to Treatment (SBIRT). Young adults in recovery may have an important role to play in delivering these innovations. However, clinics, schools, and community programs may face barriers when implementing new prevention and early intervention approaches in their settings. The purpose of this study is to examine the feasibility, barriers, and facilitators of Project Amp, an innovative, four-session prevention and early intervention model to enhance SBIRT for adolescents. Methods Three school-based programs and three health clinics were selected to implement SBIRT for adolescents and refer eligible adolescents (13–17 years old, moderate risk for substance use disorder) to the study intervention. Between three and six mentors (young adults, 18–28 years old, with lived experience of substance use recovery, also known as peers), were recruited at each site and trained in core skills to deliver the intervention. Study staff communicated with each setting throughout implementation and collected quantitative and qualitative data regarding facilitators and barriers to success. The qualitative data were analyzed to identify key strategies for success when implementing Project Amp. Results Across the six sites, 71 practitioners including physicians, nurses, social workers, and counselors, completed training in SBIRT and 30 mentors were hired and trained for the study. Twenty completed sessions with adolescent participants. A total of 1192 adolescents were screened using the CRAFFT. Of those screened, 139 (12%) were eligible, 51 eligible youth (37%) enrolled in the study, and 28 enrolled youth (55%) completed the intervention. Five of the six sites were successfully able to integrate the SBIRT-based Project Amp model into their workflow. Facilitators and barriers for implementation were identified related to three critical factors: recruitment, readiness, and sustainability. Conclusions The Project Amp intervention can be conducted successfully in school and healthcare settings in conjunction with SBIRT, adding capacity to expand access to screening and early intervention in a developmentally appropriate way. However, the study yielded insights into adaptations for future implementation, such as a more streamlined model and centralized staff roles such as integrated roles for young peer mentors.

Biosimilar filgrastims are primarily indicated for chemotherapy-induced neutropenia prevention. They are less expensive formulations of branded filgrastim, and biosimilar filgrastim was the first biosimilar oncology drug administered in European Union (EU) countries, Japan, and the U.S. Fourteen biosimilar filgrastims have been marketed in EU countries, Japan, the U.S., and Canada since 2008, 2012, 2015, and 2016, respectively. We reviewed experiences and policies for biosimilar filgrastim markets in EU countries and Japan, where uptake has been rapid, and in the U.S. and Canada, where experience is rapidly emerging. U.S. regulations for designating biosimilar interchangeability are under development, and such regulations have not been developed in most other countries. Pharmaceutical substitution is allowed for new filgrastim starts in some EU countries and in Canada, but not Japan and the U.S. In EU countries, biosimilar adoption is facilitated with favorable hospital tender offers. U.S. adoption is reportedly 24%, while the second filgrastim biosimilar is priced 30% lower than branded filgrastim and 20% lower than the first biosimilar filgrastim approved by the U.S. Food and Drug Administration. Utilization is about 60% in EU countries, where biosimilar filgrastim is marketed at a 30%–40% discount. In Japan, biosimilar filgrastim utilization is 45%, primarily because of 35% discounts negotiated by Central Insurance and hospital-only markets. Overall, biosimilar filgrastim adoption barriers are small in many EU countries and Japan and are diminishing in Canada in the U.S. Policies facilitating improved U.S. adoption of biosimilar filgrastim, based on positive experiences in EU countries and Japan, including favorable insurance coverage; larger price discount relative to reference filgrastim pricing; closing of the “rebate trap” with transparent pricing information; formal educational efforts of patients, physicians, caregivers, and providers; and allowance of pharmaceutical substitution of biosimilar versus reference filgrastim, should be considered. Implications for Practice We reviewed experiences and policies for biosimilar filgrastims in Europe, Japan, Canada, and the U.S. Postmarketing harmonization of regulatory policies for biosimilar filgrastims has not occurred. Acceptance of biosimilar filgrastims for branded filgrastim, increasing in the U.S. and in Canada, is commonplace in Japan and Europe. In the U.S., some factors, accepted in Europe or Japan, could improve uptake, including acceptance of biosimilars as safe and effective; larger cost savings, decreasing “rebate traps” where pharmaceutical benefit managers support branded filgrastim, decreased use of patent litigation/challenges, and allowing pharmacists to routinely substitute biosimilar for branded filgrastim.

Root traits get increasing attention as functional equivalents of above‐ground traits. Image analysis software such as WinRhizo™ and IJ_Rhizo facilitate root trait analyses. Delory et al. (2017) presented a comparison between the accuracy of WinRhizo™ and IJ_Rhizo for measuring root length. We complement their analyses with a comparison of diameter and volume estimates and a comparison of different image resolutions with manual and automatic threshold. We analysed 100 images of fibrous and taproot systems, which were obtained using the root model ArchiSimple. As a result, for each image, diameter, length and volume were known. The images were analysed with WinRhizo™ and IJ_Rhizo and we compared the estimates of diameter, length and volume to ground‐truth values. We further computed relative errors and their magnitude and analysed their dependency on image characteristics and root system properties. At 1,200 and 800 dpi, diameter and length estimates provided by WinRhizo™ and IJ_Rhizo were of comparable accuracy. Diameter errors were balanced. Volume estimates were subjected to a systematic error caused by the assumption of constant diameter. WinRhizo™, however, provides the opportunity to calculate correctly computed volumes from diameter classes. At 1,200 dpi, IJ_Rhizo failed to automatically find an appropriate threshold for pixel classification, which fundamentally decreased accuracy. The magnitude of diameter errors increased with root overlap for IJ_Rhizo. The length errors increased with increasing root length, overlap and root length density for WinRhizo™. The magnitude of underestimation of the volume (WinRhizo™) decreased with volume. It was higher for taproot than for fibrous root systems. All errors increased with lower resolution. Our results confirm the results of Delory et al. (2017) regarding the accuracy for length. They further confirm that estimates derived from different software packages or at different resolution should not be compared directly. The characteristics of root systems should be standardized for image analysis. The dependency of errors on the response variable of interest can influence the effect size and increase the probability of errors. Validation of methods should be conducted for each analysed dataset. New image analysis tools should be validated against a real ground‐truth.

SummaryFinding, characterizing, and monitoring reservoirs for antimicrobial resistance (AMR) is vital to protecting public health. Hybridization capture baits are an accurate, sensitive, and cost-effective technique used to enrich and characterize DNA sequences of interest, including antimicrobial resistance genes (ARGs), in complex environmental samples. We demonstrate the continued utility of a set of 19,933 hybridization capture baits designed from the Comprehensive Antibiotic Resistance Database (CARD)v1.1.2 and Pathogenicity Island Database (PAIDB)v2.0, targeting 3,565 unique nucleotide sequences that confer resistance. We demonstrate the efficiency of our bait set on a custom-made resistance mock community and complex environmental samples to increase the proportion of on-target reads as much as >200-fold. However, keeping pace with newly discovered ARGs poses a challenge when studying AMR, because novel ARGs are continually being identified and would not be included in bait sets designed prior to discovery. We provide imperative information on how our bait set performs against CARDv3.3.1, as well as a generalizable approach for deciding when and how to update hybridization capture bait sets. This research encapsulates the full life cycle of baits for hybridization capture of the resistome from design and validation (both in silico and in vitro) to utilization and forecasting updates and retirement.Originality-Significance StatementThis work is applicable to a wide range of research. It helps to define conditions under which hybridization capture is useful regarding not only antimicrobial resistance specifically, but also more generally how to assess the ongoing utility of existing bait sets - giving objective criteria for when and by what strategies baits should be updated. We also provide a method for quantifying and comparing antimicrobial resistance genes (ARGs) similar to what is used for RNAseq experiments. This approach improves comparison of ARGs across environments. Thus, the work provides an improved foundation for ARG future studies, while cutting across traditional areas of microbiology and extending beyond.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019, and the outbreak rapidly evolved into the current coronavirus disease pandemic. SARS-CoV-2 is a respiratory virus that causes symptoms similar to those caused by influenza A and B viruses. On July 2, 2020, the US Food and Drug Administration granted emergency use authorization for in vitro diagnostic use of the Influenza SARS-CoV-2 Multiplex Assay. This assay detects influenza A virus at 102.0, influenza B virus at 102.2, and SARS-CoV-2 at 100.3 50% tissue culture or egg infectious dose, or as few as 5 RNA copies/reaction. The simultaneous detection and differentiation of these 3 major pathogens increases overall testing capacity, conserves resources, identifies co-infections, and enables efficient surveillance of influenza viruses and SARS-CoV-2.

Missed Connections is a collection of short stories exploring queer and peculiar women navigating the minutae of their existences in cities across southern Ontario; Hamilton, Burlington, and Windsor, in particular. Missed Connections navigates the complexities of identities that are mutable and in flux, reflected in part through the youthful state of most of the protagonists. Some stories in Missed Connections include: “Stick-N-Poke” which follows a bisexual high-school drop-out who struggles with addiction and infatuation, “Ephemera” in which a militant lesbian unwittingly falls for a drag queen and meditates on desire, and a triptych, which is composed of “Catfish,” “Vernacular,” and “One New Message” an ironic bildungsroman following a fat straight white girl’s pursuit of authenticity. Missed Connections asks what it means to be here, now.

Topographic sensory representations often do not scale proportionally to the size of their input regions, with some expanded and others contracted. In vision, the foveal representation is magnified cortically, as are the fingertips in touch. What principles drive this allocation, and how should receptor density, e.g. the high innervation of the fovea or the fingertips, and stimulus statistics, e.g. the higher contact frequencies on the fingertips, contribute? Building on work in efficient coding, we address this problem using linear models that maximize information transmission through decorrelation. We introduce a sensory bottleneck to impose constraints on resource allocation and derive the optimal neural allocation. We find that bottleneck width is a crucial factor in resource allocation, inducing either expansion or contraction. Both receptor density and stimulus statistics affect allocation and jointly determine convergence for wider bottlenecks. Furthermore, we show a close match between the predicted and empirical cortical allocations in a well-studied model system, the star-nosed mole. Overall, our results suggest that the strength of cortical magnification depends on resource limits.

International audience; The effects of plants on the biosphere, atmosphere and geosphere are key determinants of terrestrial ecosystem functioning. However, despite substantial progress made regarding plant belowground components, we are still only beginning to explore the complex relationships between root traits and functions. Drawing on the literature in plant physiology, ecophysiology, ecology, agronomy and soil science, we reviewed 24 aspects of plant and ecosystem functioning and their relationships with a number of root system traits, including aspects of architecture, physiology, morphology, anatomy, chemistry, biomechanics and biotic interactions. Based on this assessment, we critically evaluated the current strengths and gaps in our knowledge, and identify future research challenges in the field of root ecology. Most importantly, we found that belowground traits with the broadest importance in plant and ecosystem functioning are not those most commonly measured. Also, the estimation of trait relative importance for functioning requires us to consider a more comprehensive range of functionally relevant traits from a diverse range of species, across environments and over time series. We also advocate that establishing causal hierarchical links among root traits will provide a hypothesis-based framework to identify the most parsimonious sets of traits with the strongest links on functions, and to link genotypes to plant and ecosystem functioning.

In the context of a recent massive increase in research on plant root functions and their impact on the environment, root ecologists currently face many important challenges to keep on generating cutting-edge, meaningful and integrated knowledge. Consideration of the below-ground components in plant and ecosystem studies has been consistently called for in recent decades, but methodology is disparate and sometimes inappropriate. This handbook, based on the collective effort of a large team of experts, will improve trait comparisons across studies and integration of information across databases by providing standardised methods and controlled vocabularies. It is meant to be used not only as starting point by students and scientists who desire working on below-ground ecosystems, but also by experts for consolidating and broadening their views on multiple aspects of root ecology. Beyond the classical compilation of measurement protocols, we have synthesised recommendations from the literature to provide key background knowledge useful for: (1) defining below-ground plant entities and giving keys for their meaningful dissection, classification and naming beyond the classical fine-root vs coarse-root approach; (2) considering the specificity of root research to produce sound laboratory and field data; (3) describing typical, but overlooked steps for studying roots (e.g. root handling, cleaning and storage); and (4) gathering metadata necessary for the interpretation of results and their reuse. Most importantly, all root traits have been introduced with some degree of ecological context that will be a foundation for understanding their ecological meaning, their typical use and uncertainties, and some methodological and conceptual perspectives for future research. Considering all of this, we urge readers not to solely extract protocol recommendations for trait measurements from this work, but to take a moment to read and reflect on the extensive information contained in this broader guide to root ecology, including sections I–VII and the many introductions to each section and root trait description. Finally, it is critical to understand that a major aim of this guide is to help break down barriers between the many subdisciplines of root ecology and ecophysiology, broaden researchers’ views on the multiple aspects of root study and create favourable conditions for the inception of comprehensive experiments on the role of roots in plant and ecosystem functioning. ISSN:0028-646X ISSN:1469-8137

Ovarian cancer is a lethal disease that urgently requires new therapies. This thesis provides new insight into the role of a protein called DPP4 in ovarian cancer. The studies in this thesis show that DPP4 has potential as a marker for ovarian cancer progression or response to therapy. Targeting DPP4 using a drug called sitagliptin could improve the immune response in patients with late-stage ovarian cancer and shows promise when combined with other therapies. This research shows that using sitagliptin to target DPP4 in ovarian cancer should be considered in clinical trials to improve outcomes for women with this disease.

An extreme summer drought caused unprecedented tree dieback across Central Europe in 2018, highlighting the need for a better mechanistic understanding of drought-induced tree mortality. While numerous physiological risk factors have been identified, the principal mechanisms, hydraulic failure and carbon starvation, are still debated. We studied 9,435 trees from 12 temperate species planted in a diversity experiment in 2013 to assess how hydraulic traits, carbon dynamics, pest infestation, tree height and neighbourhood competition influence individual mortality risk. We observed a reduced mortality risk for trees with wider hydraulic safety margins, while a rising sugar fraction of the non-structural carbohydrate pool and bark beetle infestation were associated with higher risk. Taller trees had a lower mortality risk. The sign and magnitude of neighbourhood effects on mortality risk depended on the species-identity of the involved trees, with most species having beneficial and some having deleterious effects on their neighbours. While severe tissue dehydration causing hydraulic failure precedes drought-induced tree mortality, we show that the probability of this event depends on a series of mutually inclusive processes including pest infestation and starch depletion for osmotic adjustment, and is modulated by the size and species identity of a tree and its neighbours.

Individual fingers in the primary somatosensory cortex (S1) are known to be represented separately and adjacently, forming a cortical hand map. Electrophysiological studies in monkeys show that finger amputation triggers increased selectivity to the neighbouring fingers within the deprived S1, causing local reorganisation. Neuroimaging research in humans, however, shows persistent S1 finger representation of the missing hand, even decades after amputation. We aimed to resolve these apparently contrasting evidence by examining finger representation in humans following pharmacological ‘amputation’ using single-finger nerve block and 7T neuroimaging. We hypothesised that beneath the apparent selectivity of individual fingers in the hand map, peripheral and central processing is distributed across fingers. If each finger contributes to the cortical representation of the others, then localised input loss will weaken finger representation across the hand map. For the same reason, the non-blocked fingers will stabilise the blocked finger’s representation, resulting in persistent representation of the blocked finger. Using univariate selectivity profiling, we replicated the electrophysiological findings of local S1 reorganisation. However, more comprehensive analyses confirmed that local blocking reduced representation of all fingers across the entire hand area. Importantly, multivariate analysis demonstrated that despite input loss, representation of the blocked finger remained persistent and distinct from the unblocked fingers. Computational modelling suggested that the observed findings are driven by distributed processing underlying the topographic map, combined with homeostatic mechanisms. Our findings suggest that the long-standing depiction of the somatosensory hand map is misleading. As such, accounts for map reorganisation, e.g. following amputation, need to be reconsidered.

Submitted by Igor Pereira (igor.spereira@uniceub.br) on 2021-01-19T19:44:28Z No. of bitstreams: 1 Laura Oliveira 21603463.pdf: 369355 bytes, checksum: ddd89b97d9e4bca8ec310806eaee0876 (MD5) Approved for entry into archive by Fernanda Weschenfelder (fernanda.weschenfelder@uniceub.br) on 2021-03-23T15:30:07Z (GMT) No. of bitstreams: 1 Laura Oliveira 21603463.pdf: 369355 bytes, checksum: ddd89b97d9e4bca8ec310806eaee0876 (MD5) Made available in DSpace on 2021-03-23T15:30:07Z (GMT). No. of bitstreams: 1 Laura Oliveira 21603463.pdf: 369355 bytes, checksum: ddd89b97d9e4bca8ec310806eaee0876 (MD5) Previous issue date: 2021-01-19 O presente trabalho visa demonstrar o potencial de elementos culturais como instrumento de política pública para educar, ressocializar e resgatar a dignidade humana dos indivíduos que se encontram em cumprimento de penas nas penitenciárias brasileiras. O método exploratório foi utilizado em pesquisa bibliográfica com o propósito de reunir argumentos para o debate. O método pedagógico emancipatório para compor a política criminal alternativa foi proposto pelo minimalismo penal de Alessandro Baratta com a finalidade de humanizar as penasdaquelesqueseencontrampresos,aproximaracomunidade carcerária da sociedade civil e fazê-los refletirem e se integrarem a um sistema que sistema que reflete e mantém a desigualdade social

Understanding the persistence of enveloped viruses helps inform infection control practices and procedures in health care facilities and community settings. These data convey to public health investigators that enveloped viruses can persist and remain infective on surfaces, thus demonstrating a potential risk for transmission. Under these laboratory-simulated Western indoor hospital conditions, we assessed the suitability of phi 6 as a surrogate for environmental persistence research related to enveloped viruses, including EBOV and coronaviruses., The infection of health care workers during the 2013 to 2016 Ebola outbreak raised concerns about fomite transmission. In the wake of the coronavirus disease 2019 (COVID-19) pandemic, investigations are ongoing to determine the role of fomites in coronavirus transmission as well. The bacteriophage phi 6 has a phospholipid envelope and is commonly used in environmental studies as a surrogate for human enveloped viruses. The persistence of phi 6 was evaluated as a surrogate for Ebola virus (EBOV) and coronaviruses on porous and nonporous hospital surfaces. Phi 6 was suspended in a body fluid simulant and inoculated onto 1-cm2 coupons of steel, plastic, and two fabric curtain types. The coupons were placed at two controlled absolute humidity (AH) levels: a low AH of 3.0 g/m3 and a high AH of 14.4 g/m3. Phi 6 declined at a lower rate on all materials under low-AH conditions, with a decay rate of 0.06-log10 PFU/day to 0.11-log10 PFU/day, than under the higher AH conditions, with a decay rate of 0.65-log10 PFU/h to 1.42-log10 PFU/day. There was a significant difference in decay rates between porous and nonporous surfaces at both low AH (P

Biosimilars are biologic drug products that are highly similar to reference products in analytic features, pharmacokinetics and pharmacodynamics, immunogenicity, safety, and efficacy. Biosimilar epoetin received Food and Drug Administration (FDA) approval in 2018. The manufacturer received an FDA nonapproval letter in 2017, despite receiving a favorable review by FDA's Oncologic Drugs Advisory Committee (ODAC) and an FDA nonapproval letter in 2015 for an earlier formulation. We discuss the 2018 FDA approval, the 2017 FDA ODAC Committee review, and the FDA complete response letters in 2015 and 2017; review concepts of litigation, naming, labeling, substitution, interchangeability, and pharmacovigilance; review European and U.S. oncology experiences with biosimilar epoetin; and review the safety of erythropoiesis-stimulating agents. In 2020, policy statements from AETNA, United Health Care, and Humana indicated that new epoetin oncology starts must be for biosimilar epoetin unless medical need for other epoetins is documented. Empirical studies report that as of 2012, reference epoetin use decreased from 40%–60% of all patients with cancer with chemotherapy-induced anemia to Implications for Practice Few oncologists understand substitution and interchangeability of biosimilars with reference drugs. Epoetin biosimilar is new to the market, and physician and patient understanding is limited. The development of epoetin biosimilar is not familiar to oncologists.

Erythropoisis stimulating agent (ESA) use was addressed in Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) meetings between 2004 and 2008. FDA safety-focused regulatory actions occurred in 2007 and 2008. In 2007, black box warnings advised of early death and venous thromboembolism (VTE) risks with ESAs in oncology. In 2010, a Risk Evaluation Strategies (REMS) was initiated, with cancer patient consent that mortality and VTE risks were noted with ESAs. We report warnings and REMS impacts on ESA utilization among Veterans Administration (VA) cancer patients with chemotherapy-induced anemia (CIA). Data were from Veterans Affairs database (2003-2012). Epoetin and darbepoetin use were primary outcomes. Segmented linear regression was used to estimate changes in ESA use levels and trends, clinical appropriateness, and adverse events (VTEs) among chemotherapy-treated cancer patients. To estimate changes in level of drug prescription rate after policy actions, model-specific indicator variables as covariates based on specific actions were included. ESA use fell by 95% and 90% from 2005, for epoetin and darbepoetin, from 22% and 11%, respectively, to 1% and 1%, respectively, among cancer patients with CIA, respectively (p

Depression is a common and debilitating disease in pediatric patients with life-limiting illnesses. Depression can be challenging to diagnose in patients with advanced illness because symptoms can be difficult to recognize. Evaluation for depression in this population should focus on the cognitive or psychological, rather than physical, symptoms. Treatment for depression can positively impact quality of life and should be instituted promptly. Clinicians should consider patient prognosis to help guide therapy selection because usual antidepressant medications require several weeks to take full effect, whereas psychostimulants have a much faster onset. The most effective treatment for depression should also incorporate nonpharmacologic therapies and utilize the support of the interdisciplinary palliative care team. This chapter explores the nuances of diagnosing as well as treating depression in pediatric palliative care patients.

Magnetic particle imaging (MPI) is a novel medical imaging modality that spatially detects a tracer of superparamagnetic iron oxide nanoparticles (SPIOs) with high sensitivity, contrast, and no tissue penetration limitations. MPI has great potential for safer angiography, in vivo cell tracking, and cancer detection, among other applications. Current MPI theoretical descriptions and reconstruction techniques make an adiabatic assumption that the SPIO tracer instantaneously follows the applied magnetic fields of the MPI scanner. This assumption is not strictly true, and we refer to SPIO magnetization delays as relaxation effects.We begin by extending the x-space theory of MPI to include relaxation effects. We choose this MPI theory because it directly converts the temporal MPI signal to the image (spatial) domain, lending itself well to investigating how relaxation time delays translate into spatial effects. Using the non-adiabatic x-space theory and experimentally-measured data, we demonstrate that relaxation blurs the x-space image in the scanning direction. Next, we study how we may design MPI scanning sequences to minimize relaxation-induced blurring. From the non-adiabatic x-space theory we derive a mathematical description of how this blur can vary with scanning parameters for a given relaxation time. We compare theoretical predictions to experimental data by measuring relaxation times and spatial resolution under various scanning conditions. Despite increased relaxation time delays with slower scanning conditions, we observe that relaxation-induced blurring can be minimized when scanning slower. Finally, we derive a magnetic field-driven relaxation mechanism called magneto-viscous relaxation. This mechanism describes how the applied magnetic field creates a magnetic torque on the SPIO, inducing physical rotation of the SPIO to align with the field; however viscous resistance of the carrier liquid hinders this movement. We compare predicted relaxation times to measured values for a range of SPIO characteristics and scanning conditions. In this dissertation, we show how relaxation can have deleterious effects on the MPI signal and image. We explore how relaxation-induced blurring and relaxation times may be minimized through improved SPIO characteristics and MPI scanning sequence design. In addition to improving MPI image quality, this important area of research can lead to future clinical applications. Using this knowledge and specially-designed MPI pulse sequences, we can exploit variations in relaxation behavior as a source of contrast, which will increase the diagnostic potential of MPI.

How is spirituality, which refers to the emotional connection to the transcendent, related to compassion and to altruistic behavior towards strangers? Are the effects of spirituality different from those of religiosity, which refers to living according to the rules and rituals of religion? We hypothesized that, even though correlated, spirituality and religiosity would have different associations with compassion and altruistic behavior. The first two studies documented that more spiritual individuals experience greater compassion, and that this effect was specific to spirituality and could not be explained by religiosity. Because compassion has the capacity to motivate people to transcend selfish motives and act in altruistic fashion towards strangers, we reasoned that spirituality (but not religiosity) would predict altruistic behavior and that this link would be explained, in part, by compassion. Indeed, Studies 3, 4, and 5 found that more spiritual individuals behaved more altruistically in economic choice and decision-making tasks, and that the tendency of spiritual individuals to feel greater compassion mediated the relationship between spirituality and altruistic behavior. In contrast, more religious participants did not consistently feel more compassion nor behave more altruistically. Together, these findings help clarify why spirituality produces more prosocial behavior.

Risk of inhalation exposure to viable Bacillus anthracis (B. anthracis) spores has primarily been assessed using short-term, stationary sampling methods which may not accurately characterize the concentration of inhalable-sized spores reaching a person’s breathing zone. While a variety of aerosol sampling methods have been utilized during previous anthrax responses, no consensus has yet been established for personal air sampling. The goal of this study was to determine the best sampler-filter combination(s) for the collection and extraction of B. anthracis spores. The study was designed to (1) evaluate the performance of four filter types (one mixed cellulose ester, MCE (pore size = 3 µm), two polytetrafluoroethylene, PTFE (1 and 3 µm), and one polycarbonate, PC (3 µm)); and (2) evaluate the best performing filters in two commercially available inhalable aerosol samplers (IOM and Button). Bacillus thuringiensis kurstaki [Bt(k)], a simulant for B. anthracis, served as the aerosol challenge. The filters were assessed based on criteria such as ability to maintain low pressure drop over an extended sampling period, filter integrity under various environmental conditions, spore collection and extraction efficiencies, ease of loading and unloading the filters into the samplers, cost, and availability. Three of the four tested collection filters—except MCE—were found suitable for efficient collection and recovery of Bt(k) spores sampled from dry and humid as well as dusty and clean air environments for up to 8 hr. The PC (3 µm) filter was identified as the best performing filter in this study. The PTFE (3 µm) demonstrated a comparable performance, but it is more expensive. Slightly higher concentrations were measured with the IOM inhalable sampler which is the preferred sampler’s performance criterion when detecting a highly pathogenic agent with no established “safe” inhalation exposure level. Additional studies are needed to address the effects of environmental conditions and spore concentration. The data obtained in this investigation are crucial for future efforts on the development and optimization of a method for assessing inhalation exposure to B. anthracis.

A 43‐year‐old female with multiple sclerosis developed urethral melanoma. The only potential risk factor was treatment with natalizumab, a humanized monoclonal antibody against α4 integrins. To investigate the risk‐exposure relationship, we reviewed this case, all other published cases, and cases of natalizumab‐associated melanoma reported to regulatory agencies. Data sources included the Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) (2004–2014), a FDA Advisory Committee Meeting Report, and peer‐reviewed publications. In the United States, the manufacturer maintains an FDA‐mandated Tysabri Safety Surveillance Program (part of the Tysabri Outcomes Unified Commitment to Health (TOUCH)) of natalizumab‐treated patients. We statistically compared reporting completeness for natalizumab‐associated melanoma cases in FAERs for which information was obtained entirely from the TOUCH program versus cases where FAERS information was supplemented by TOUCH program information. FAERS included 137 natalizumab‐associated melanoma reports in patients with multiple sclerosis. Median age at melanoma diagnosis was 45 years (range: 21–74 years). Changes in preexisting nevi occurred in 16%, history of cutaneous nevi occurred in 22%, diagnosis within 2 years of beginning natalizumab occurred in 34%, and 74% had primary surgical treatment. Among seven natalizumab‐treated MS patients who developed biopsy‐confirmed melanoma on treatment and reported in the literature, median age at diagnosis was 41 years (range: 38–48 years); and the melanoma diagnosis occurred following a median of 12 natalizumab doses (range: 1–77 doses). A history of mole or nevi was noted in four patients and a history of prior melanoma was noted in one patient. Completeness scores for reports were significantly lower for FAERS cases reported from the TOUCH program versus FAERS cases supplemented by TOUCH information (median score of 2 vs. 4 items out of 8‐possible items, P

In 2018, Central Europe experienced one of the most severe and long-lasting summer drought and heat wave ever recorded. Before 2018, the 2003 millennial drought was often invoked as the example of a “hotter drought”, and was classified as the most severe event in Europe for the last 500 years. First insights now confirm that the 2018 drought event was climatically more extreme and had a greater impact on forest ecosystems of Austria, Germany and Switzerland than the 2003 drought. Across this region, mean growing season air temperature from April to October was more than 3.3°C above the long-term average, and 1.2 °C warmer than in 2003. Here, we present a first impact assessment of the severe 2018 summer drought and heatwave on Central European forests. In response to the 2018 event, most ecologically and economically important tree species in temperate forests of Austria, Germany and Switzerland showed severe signs of drought stress. These symptoms included exceptionally low foliar water potentials crossing the threshold for xylem hydraulic failure in many species and observations of widespread leaf discoloration and premature leaf shedding. As a result of the extreme drought stress, the 2018 event caused unprecedented drought-induced tree mortality in many species throughout the region. Moreover, unexpectedly strong drought-legacy effects were detected in 2019. This implies that the physiological recovery of trees was impaired after the 2018 drought event, leaving them highly vulnerable to secondary drought impacts such as insect or fungal pathogen attacks. As a consequence, mortality of trees triggered by the 2018 events is likely to continue for several years. Our assessment indicates that many common temperate European forest tree species are more vulnerable to extreme summer drought and heat waves than previously thought. As drought and heat events are likely to occur more frequently with the progression of climate change, temperate European forests might approach the point for a substantial ecological and economic transition. Our assessment also highlights the urgent need for a pan-European ground-based monitoring network suited to track individual tree mortality, supported by remote sensing products with high spatial and temporal resolution to track, analyse and forecast these transitions. ISSN:1439-1791 ISSN:1618-0089

Over the last three decades, state governments have been challenged by financial recessions. With limited resources, it is not surprising that taxpayers demanded greater accountability over state funds, and neoliberalism, a political ideology that prefaces a strong economy and individual marketplace choices, spread. Scholars have argued that performancebased funding (PBF) policies for higher education, which ties financial resources to specific metrics of achievement, is a result of that spread. In contemporary literature, scholars are examining the impacts of PBF and limitations, especially for community colleges, Historically Black Colleges and Universities, and Minority-Serving Institutions. Research on the PBF policymaking process, however, has been limited, especially from a critical perspective. From the Critical Theory research paradigm and a Critical Policy Analysis theoretical lens, this qualitative case study critically examined how policymakers approach their decisions on PBF and how they understand PBF. This study utilized Kingdon’s (1984) agenda setting theory and Stones’ (2012) approach to policy decision making to situate the nuances of policymaking. This case study (Merriam, 1998) included interviewing policymakers across five states and reviewing PBF policy-related documents. The final analysis presented four narratives and included a critical examination of issues related to power and equity. In the findings, policymakers described themselves as influencers, who balance control over higher education in order to solve problems. They practiced decision-making under feelings of urgency and tension, but with clear goals for accountability and the economy. Interestingly, policymakers described PBF as a tool designed to be flexible in order to distribute resources based on specific performances, which can include equity. Neoliberalist-based words were frequently used in goal-setting decisions for education and institutions. In contrast, equity-based words were sparingly used. Policymakers felt PBF supports their state plans for a thriving economy and disclosed an active discussion on equity for underrepresented students. However, a gap existed between dialogue and practice. Though they were aware of policy feedback on equity-based concerns for institutional types, they revealed divergent views on whether or not institutions that serve underrepresented students deserve special protection. In these discussions, no policy alternatives were offered, but a policy window (Kingdon, 1984) may open.

Neutron monitors are among the most robust and reliable detectors of GeV cosmic rays and aresensitive, with high precision, to modulations in Galactic Cosmic Rays (GCR). Hence, they canbe deployed for extended periods of time, decades, and are able to observe the modulation of GCRover many solar cycles. The South Pole Neutron Monitor, located at the geographic South Pole,which is both high latitude and high altitude, has an atmospheric cutoff of around 0.1 GV. In thefirst four decades of its operation, a secular decline in the neutron rates have been observed. Thedecline may have leveled off recently. Environmental effects, including snow build up around thehousing platform and the emergence and relocation of structures at the South Pole have been ruledout as causes of the decline. A recent study challenged the assumption that geomagnetic effectscan be ignored at the South Pole, in particular for cosmic rays approaching from select regions inazimuth and at large zenith angles. This work confirms that ignoring geomagnetic cutoff effectscould be important for the South Pole Neutron Monitor rates. We extend the investigation toinclude particle propagation in the Polar atmosphere, and the evolution of cosmic ray cutoffs atthe South Pole over several decades. A connection is made between the evolving cutoffs and thedecline in neutron monitor rates.

Background Globally, the rising cost of anticancer therapy has motivated efforts to quantify the overall value of new cancer treatments. Multicriteria decision analysis offers a novel approach to incorporate multiple criteria and perspectives into value assessment. Methods The authors recruited a diverse, multistakeholder group who identified and weighted key criteria to establish the drug assessment framework (DAF). Construct validity assessed the degree to which DAF scores were associated with past pan-Canadian Oncology Drug Review (pCODR) funding recommendations and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS; version 1.1) scores. Results The final DAF included 10 criteria: overall survival, progression-free survival, response rate, quality of life, toxicity, unmet need, equity, feasibility, disease severity, and caregiver well-being. The first 5 clinical benefit criteria represent approximately 64% of the total weight. DAF scores ranged from 0 to 300, reflecting both the expected impact of the drug and the quality of supporting evidence. When the DAF was applied to the last 60 drugs (with reviewers blinded) reviewed by pCODR (2015-2018), those drugs with positive pCODR funding recommendations were found to have higher DAF scores compared with drugs not recommended (103 vs 63; Student t test P = .0007). DAF clinical benefit criteria mildly correlated with ESMO-MCBS scores (correlation coefficient, 0.33; 95% CI, 0.009-0.59). Sensitivity analyses that varied the criteria scores did not change the results. Conclusions Using a structured and explicit approach, a criterion-based valuation framework was designed to provide a transparent and consistent method with which to value and prioritize cancer drugs to facilitate the delivery of affordable cancer care.

Horizontal transfer of supernumerary or lineage-specific (LS) chromosomes has been described in a number of plant pathogenic filamentous fungi. So far it was not known whether transfer is restricted to chromosomes of certain size or properties, or whether 'core' chromosomes can also undergo horizontal transfer. We combined a directed and a non-biased approach to determine whether such restrictions exist. Selection genes were integrated into the genome of a strain of Fusarium oxysporum pathogenic on tomato, either targeted to specific chromosomes by homologous recombination or integrated randomly into the genome. By testing these strains for transfer of the marker to another strain we could confirm transfer of a previously described mobile pathogenicity chromosome. Surprisingly, we also identified strains in which (parts of) core chromosomes were transferred. Whole genome sequencing revealed that this was accompanied by the loss of the homologous region from the recipient strain. Remarkably, transfer of the mobile pathogenicity chromosome always accompanied this exchange of core chromosomes.

Background: Contaminated healthcare surfaces can serve as reservoirs for the transmission of pathogens. Sensitive sampling methods are needed to investigate sources of pathogens for implementing effective disinfection strategies and thereby preventing environmental transmission. Conventional approaches employ swabs to sample environmental surfaces. Contact plates represent an alternative approach for sampling healthcare surfaces that does not require lab processing, though little is known about their performance. A contact plate is an agar plate that is overfilled with selective or nonselective media. It can be gently applied to the surface, then simply incubated at a temperature optimal for target organism (s), thus saving time and resources. Methods: In this study, contact plates containing trypticase soy agar with 5% sheep blood (TSAII), foam swabs, and flocked swabs were evaluated for their ability to recover 4 pathogens that persist on healthcare surfaces. Stainless-steel coupons (4 in2) were inoculated with the following pathogens (102 CFU): Acinetobacter baumannii (AB, strain type 12), carbapenemase-producing KPC+ Klebsiella pneumoniae (KP; ATCC BAA-1705); methicillin-resistant Staphylococcus aureus (MRSA; ATCC 43300); and vancomycin-resistant Enterococcus faecalis (VRE; Van A + 256). The plates were allowed to dry 1 hour. Sampling with CPs was performed in 2 ways; (1) a single contact plate was used to sample 1 stainless-steel surface and (2) a composite was collected by 3 sequential contact-plate samplings of the same stainless-steel surface. The contact plates were then incubated at 351C. Foam and flocked swabs were premoistened with phosphate-buffered saline + 0.02% polysorbate 80 (PBST) and were used to sample the stainless-steel coupons. Swabs were held for 1 hour and processed by sonication and vortexing in 5 mL of PBST, then the eluent was cultured and CFU counted. Mean percentage recoveries (%R) relative to the inoculum were calculated and compared. Results: When the %R for all 4 pathogens were pooled, the composite contact-plate sampling method yielded the highest, (P < .05) (66.0%; SD, 0.22), followed by the single contact plate method (39.7%; SD, 0.12), foam swab (32.9%; SD, 0.18), and flocked swab (20.3%; SD, 0.20). The composite contact plate method yielded the highest %R for VRE (102.1 %; SD, 0.17), and the lowest %R was observed when using flocked swabs to recover KP (6.3%; SD, 0.05). Conclusions: The contact-plate composite method may provide investigators with minimal environmental microbiology capacity an alternative method for environmental sampling and detection of organisms from surface areas (4 in 2) with low bioburden.Funding: NoneDisclosures: None

Substance use among adolescents is associated with a range of negative outcomes and risk-taking behaviors. Identifying and intervening early is essential to reducing associated risks in adolescence and adulthood. New approaches are needed to equip youth-serving systems with tools to identify and respond to substance use. Screening, Brief Intervention, and Referral to Treatment (SBIRT) has emerged as a promising public health framework and there is a growing research interest in effective adaptations for its use with adolescents. However, healthcare settings, schools, and other community-based settings are slow to adapt SBIRT, citing gaps in knowledge and capacity to deliver evidence-based substance use prevention and early intervention. Further, these settings and the surrounding communities often lack the treatment and other prevention and recovery support resources needed for youth who screen as high-risk. Integrating young adult peers with personal lived experience of substance use recovery may meet this practical need. By drawing upon their shared experiences and skills developed in recovery, young adult peers can provide developmentally appropriate screening and intervention support to youth - while also providing urgently needed skills and time to under resourced settings. This article describes the value of young adult peer roles in expanding youth substance use prevention and early intervention, and features Project Amp as an example. Project Amp was designed as an extended, four-session brief intervention for low to moderate risk adolescents, delivered by trained young adult peers. Project Amp draws on best practices from peer recovery support and prevention and early intervention approaches such as SBIRT.

Recent studies have uncovered de novo mutations of the gene encoding the chromatin remodelling protein Snf2l in patients with schizophrenia, Rett-like syndrome and intellectual disability. Snf2l and its closely related protein, Snf2h, play a critical role in embryonic and post-natal brain development. Murine models lacking functional Snf2h or Snf2l point to complementary activities of these remodelers; Snf2h cKO mice present with a significantly reduced cerebellum, while Snf2l Ex6DEL (exon 6 deleted) cerebella are larger than their wild-type counterparts. Granule neuron progenitors (GNPs) isolated from Ex6DEL cerebella display delayed cell cycle exit and hindered terminal differentiation compared to wild-type controls. Moreover, loss of Snf2l activity results in widespread transcriptome shifts which underlie the Ex6DEL GNP differentiation phenotype. In particular, key transcription factors are differentially expressed without Snf2l remodelling activity. We confirm that ERK pathway activation is misregulated in Ex6DEL GNPs, possibly in response to elevated fibroblast growth factor 8 (Fgf8) expression in these cultures. We find that Snf2l activity maintains the chromatin landscape throughout GNP differentiation, as Ex6DEL cultures have a global increase in chromatin accessibility. We suggest that Snf2l-mediated chromatin condensation is responsible for proper regulation of gene expression programs in GNP differentiation.