This paper reviews methods for detecting proteins based on molecular digitization,
, the isolation and detection of single protein molecules or singulated ensembles of protein molecules. The single ...molecule resolution of these methods has resulted in significant improvements in the sensitivity of immunoassays beyond what was possible using traditional "analog" methods: the sensitivity of some digital immunoassays approach those of methods for measuring nucleic acids, such as the polymerase chain reaction (PCR). The greater sensitivity of digital protein detection has resulted in immuno-diagnostics with high potential societal impact,
, the early diagnosis and therapeutic intervention of Alzheimer's Disease. In this review, we will first provide the motivation for developing digital protein detection methods given the limitations in the sensitivity of analog methods. We will describe the paradigm shift catalyzed by single molecule detection, and will describe in detail one digital approach - which we call digital bead assays (DBA) - based on the capture and labeling of proteins on beads, identifying "on" and "off" beads, and quantification using Poisson statistics. DBA based on the single molecule array (Simoa) technology have sensitivities down to attomolar concentrations, equating to ∼10 proteins in a 200 μL sample. We will describe the concept behind DBA, the different single molecule labels used, the ways of analyzing beads (imaging of arrays and flow), the binding reagents and substrates used, and integration of these technologies into fully automated and miniaturized systems. We provide an overview of emerging approaches to digital protein detection, including those based on digital detection of nucleic acids labels, single nanoparticle detection, measurements using nanopores, and methods that exploit the kinetics of single molecule binding. We outline the initial impact of digital protein detection on clinical measurements, highlighting the importance of customized assay development and translational clinical research. We highlight the use of DBA in the measurement of neurological protein biomarkers in blood, and how these higher sensitivity methods are changing the diagnosis and treatment of neurological diseases. We conclude by summarizing the status of digital protein detection and suggest how the lab-on-a-chip community might drive future innovations in this field.
Photoprotective non-photochemical quenching (NPQ) in higher plants is the result of the formation of energy quenching traps in the light-harvesting antenna of photosystem II (PSII). It has been ...proposed that this quenching trap is a lutein molecule closely associated with the chlorophyll terminal emitter of the major light-harvesting complex LHCII. We have used a combination of time-dependent density functional theory (TD-DFT) and the semiempirical MNDO-CAS-CI method to model the chlorophyll–lutein energy transfer dynamics of the highly quenched crystal structure of LHCII. Our calculations reveal that the incoherent “hopping” of energy from Chla612 to the short-lived, dipole forbidden 21Ag – state of lutein620 accounts for the strong fluorescence quenching observed in these crystals. This adds weight to the argument that the same dissipative pathway is responsible for in vivo NPQ.
Conservation concerns exist for many sharks but robust estimates of abundance are often lacking. Improving population status is a performance measure for species under conservation or recovery plans, ...yet the lack of data permitting estimation of population size means the efficacy of management actions can be difficult to assess, and achieving the goal of removing species from conservation listing challenging. For potentially dangerous species, like the white shark, balancing conservation and public safety demands is politically and socially complex, often leading to vigorous debate about their population status. This increases the need for robust information to inform policy decisions. We developed a novel method for estimating the total abundance of white sharks in eastern Australia and New Zealand using the genetic-relatedness of juveniles and applying a close-kin mark-recapture framework and demographic model. Estimated numbers of adults are small (ca. 280-650), as is total population size (ca. 2,500-6,750). However, estimates of survival probability are high for adults (over 90%), and fairly high for juveniles (around 73%). This represents the first direct estimate of total white shark abundance and survival calculated from data across both the spatial and temporal life-history of the animal and provides a pathway to estimate population trend.
To advance emotion research in education, there is a need to develop practical and context-relevant measures of emotion and to test the applicability of emotion theories using these measures. In two ...studies, we examined validity evidence of a self-report scale (the Medical Emotion Scale, MES) designed to measure the unique range of emotions activated within medical education. In Study 1, we administered the MES and conducted interviews with medical trainees (N = 15). Content analysis of interviews demonstrated that the MES captured an appropriate range of emotions and that there was alignment between scale responses and interview responses. In Study 2, we measured medical trainees' (N = 60) emotions using the MES for three learning environments. Results from principal components analysis revealed a structure of emotions according to valence (negative, positive) and novelty. The findings have implications for the measurement of emotions within technology-rich learning environments and beyond.
The purpose of this study was to assess the effectiveness of an intervention designed to foster epistemic change over the course of 1 semester. The intervention was based on constructivist teaching ...practices that incorporated teacher modeling of critical thinking of content, evaluation of multiple approaches to solving problems, and making connections to prior knowledge. Sixty-three students across 2 classrooms (one intervention n = 31, one control n = 32) participated and completed questionnaires 5 times over the semester. Questionnaires measured students' epistemic beliefs, learning strategies, and levels of motivation for their statistics class. Results revealed that for students in the intervention class, their epistemic beliefs shifted midway through the semester, whereas students in the control group maintained a consistent level of beliefs throughout the semester. Intervention students' self-reported use of critical thinking and elaboration strategies also significantly increased midway through the semester, as did their levels of self-efficacy for learning statistics. In contrast, students in the control group maintained a consistent level of strategy use and self-efficacy. Finally, students in the intervention group had a significantly higher final grade compared with those in the control group. (Contains 3 tables, 7 figures and 1 footnote.)
Résumé
Les performances du test de diagnostic rapide (TDR) du paludisme OptiMal-IT® ont été évaluées en Mauritanie où la transmission du paludisme est faible, de type saisonnière et courte. La ...microscopie a été prise comme méthode de diagnostique de référence. L’inclusion des patients fébriles venus en consultation dans six structures sanitaires, dont trois en milieu urbain et trois en milieu rural, s’est déroulée de décembre 2011 à février 2012 et d’août 2012 à mars 2013. Au total, 780 patients ont été inclus et 759 avaient à la fois un résultat de TDR et de goutte épaisse. La lecture des 774 lames, dont 200 étaient positives, a décelé
P. falciparum
ou
P. vivax
dans les proportions respectives de 63,5 % (127/200) et 29,5 % (59/200), et la co-infection
P. falciparum/P. vivax
a représenté 7 % (14/200). Les deux espèces ont été observées dans les divers sites avec des proportions significativement différentes. Les proportions de lames porteuses d’hématozoaires du paludisme et de TDR positifs étaient respectivement de 26,3 % et 30,3 %. La sensibilité et la spécificité du TDR étaient respectivement de 89 % 84,7-93,3 et 91,1 % 88,6-93,4. Les valeurs prédictives positives et négatives étaient de 78,1 % 72,2-83,7 et 95,9 % 94,1-97,5. Les valeurs diagnostiques trouvées étaient comparables à celles généralement rapportées. Les TDR tendent à devenir le principal outil de diagnostic du paludisme en Mauritanie.
We present our perspective on the theoretical basis of light-harvesting within the photosynthetic membrane. Far from being a static structure, the photosynthetic membrane is a highly dynamic system, ...with protein mobility playing an important role in the damage/repair cycle of photosystem II (PSII), in balancing the input of energy between PSI and PSII, and in the photoprotection of PSII in response to a sudden excess of illumination. The concept of a photosynthetic antenna is illustrated and the state transition phenomenon is discussed as an example of purposeful antenna mobility. We discuss fluorescence recovery after photo-bleaching as a technique for visualising membrane mobility, before introducing light-induced grana membrane reorganisation as an integral part of the rapid photoprotective switch in plants. We then discuss current theoretical approaches to modelling the energy transfer dynamics of the PSII antenna: the atomistic models of intra-complex transfer and the coarse-grained approach to the inter-complex dynamics. Finally we discuss the future prospect of extending these methods, beyond the static picture of the membrane, to the dynamic PSII photosynthetic antenna.
The key feature of the photosynthetic membrane is its ability to change its composition and move its components in order to rearrange them into the most favourable state for efficient and safe light harvesting.
Resilience is a contextual phenomenon where a complex and dynamic interplay exists between individual, environmental, and socio-cultural factors. With growing interest in enhancing resilience in ...physicians, given their high risk for experiencing prolonged or intense stress, effective strategies are necessary to improve resilience and reduce negative outcomes including burnout. The objective of this review was to identify effective interventions to improve resilience in physicians who have completed training, working in any setting.
We included randomized controlled trials (RCT), and observational studies (including pilot studies) published in English, French, and Spanish that included an intervention to improve resilience in physicians who have completed training. We included studies that implemented interventions to reduce burnout, anxiety, and depression or to improve empathy to ultimately enhance resilience, rather than studies designed solely to reduce stress or trauma-induced stress. We performed a systematic search of Medline, EMBASE, PsychInfo, CINAHL and Cochrane Library with no publication year limit. The last search was conducted on March 29, 2017. We used random effect models to calculate pooled standardized mean differences. Resilience was the primary outcome measure using validated resilience scores. Secondary outcome measures included proxy measures of resilience such as burnout, empathy, anxiety and depression. Our search strategy identified 7,579 records;74 met the criteria for full-text review. Seventeen studies were included in the final review published between 1998 and 2016 of which 9 (4 RCT, 5 observational) had physician data extractable. Interventions varied greatly regarding their approach, duration, and follow-up. Two RCTs measured resilience using validated scales; both found a significant improvement. No meta-analysis for resilience was conducted due to the presence of high clinical and methodological heterogeneity.
Our systematic review demonstrates that there is weak evidence to support one intervention over another to improve resilience in physicians who have completed training. The quality of evidence for the outcomes ranged from very low to low. There is a need for a consensus on the definition of resilience and how it is measured. Longer follow-up is required to ensure any intervention effects are sustained over time.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ObjectivesTo explore the impact of the COVID-19 pandemic on the experiences and mental health of university students.DesignA cross-sectional study consisting of an electronic survey about students’ ...experiences and concerns during the pandemic and the associated impact. In addition to the quantitative analysis, free-text responses were extracted and analysed using a framework technique.SettingQueen’s University in Canada and the University of Oxford in the UK.ParticipantsUndergraduate students at Queen’s University and first-year undergraduate students at the University of Oxford were invited to complete the COVID-19 supplement survey. This study included data from 3013 Queen’s students as the primary focus and 339 Oxford students as a secondary comparison.ResultsFemales at Queen’s reported greater adherence to government recommendations to prevent the spread of COVID-19 (91.3% vs 86.7%, χ2 p<0.01) and were more likely to self-isolate (63.9% vs 57.0%, χ2 p<0.01) than males. A similar trend was seen among Oxford students. Students’ concerns were wide ranging including those related to their learning experience, finances and future academic and career prospects. 78.9% of Queen’s students and 50.4% of first-year Oxford students reported worries about the long-term impact on their academic and job prospects. A sizeable proportion of students also reported that the pandemic negatively impacted their plans to continue at university (29.4% of Queen’s, 14.2% of Oxford) and disrupted activities important to their mental well-being. Key themes identified in the qualitative component included the negative impacts of social isolation, challenging academic changes and disruption to support services and means of coping.ConclusionsOverall, findings underscore the importance of addressing areas of student concern and the aspects of student life negatively impacted by the pandemic in order to maintain student well-being and support a successful university experience.
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