bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying pathways for large-scale implementation of a school-based mental health programme in the Eastern Mediterranean Region: a theory-driven approach
Authors: Alonge Olakunle , Chiumento Anna , Hamoda Hesham M , Gaber Eman , Huma Zill-e- , Abbasinejad Maryam , Hosny Walaa , Shakiba Alia , Minhas Ayesha , Saeed Khalid , Wissow Lawrence , Rahman Atif
Published: September 2020

Globally there is a substantial burden of mental health problems among children and adolescents. Task-shifting/task-sharing mental health services to non-specialists, e.g. teachers in school settings, provide a unique opportunity for the implementation of mental health interventions at scale in low- and middle-income countries (LMICs). There is scant information to guide the large-scale implementation of school-based mental health programme in LMICs. This article describes pathways for large-scale implementation of a School Mental Health Program (SMHP) in the Eastern Mediterranean Region (EMR). A collaborative learning group (CLG) comprising stakeholders involved in implementing the SMHP including policymakers, programme managers and researchers from EMR countries was established. Participants in the CLG applied the theory of change (ToC) methodology to identify sets of preconditions, assumptions and hypothesized pathways for improving the mental health outcomes of school-aged children in public schools through implementation of the SMHP. The proposed pathways were then validated through multiple regional and national ToC workshops held between January 2017 and September 2019, as the SMHP was being rolled out in three EMR countries: Egypt, Pakistan and Iran. Preconditions, strategies and programmatic/contextual adaptations that apply across these three countries were drawn from qualitative narrative summaries of programme implementation processes and facilitated discussions during biannual CLG meetings. The ToC for large-scale implementation of the SMHP in the EMR suggests that identifying national champions, formulating dedicated cross-sectoral (including the health and education sector) implementation teams, sustained policy advocacy and stakeholders engagement across multiple levels, and effective co-ordination among education and health systems especially at the local level are among the critical factors for large-scale programme implementation. The pathways described in this paper are useful for facilitating effective implementation of the SMHP at scale and provide a theory-based framework for evaluating the SMHP and similar programmes in the EMR and other LMICs.
How to evaluate the implementation of complex health programmes in low-income settings: the approach of the Gavi Full Country Evaluations
Authors: Soi Caroline , Shearer Jessica C , Budden Ashwin , Carnahan Emily , Salisbury Nicole , Asiimwe Gilbert , Chilundo Baltazar , Sarma Haribondhu , Gimbel Sarah , Simuyemba Moses , Uddin Jasim , Masiye Felix , Kamya Moses , Hozumi Dai , Rajaratnam Julie K , Lim Stephen S
Published: September 2020

Vaccination, like most other public health services, relies on a complex package of intervention components, functioning systems and committed actors to achieve universal coverage. Despite significant investment in immunization programmes, national coverage trends have slowed and equity gaps have grown. This paper describes the design and implementation of the Gavi Full Country Evaluations, a multi-country, prospective, mixed-methods approach whose goal was to monitor and evaluate processes, inputs, outputs and outcomes of immunization programmes in Bangladesh, Mozambique, Uganda and Zambia. We implemented the Full Country Evaluations from 2013 to 2018 with the goal of identifying the drivers of immunization programme improvement to support programme implementation and increase equitable immunization coverage. The framework supported methodological and paradigmatic flexibility to respond to a broad range of evaluation and implementation research questions at global, national and cross-country levels, but was primarily underpinned by a focus on evaluating processes and identifying the root causes of implementation breakdowns. Process evaluation was driven by theories of change for each Gavi funding stream (e.g. Health Systems Strengthening) or activity, ranging from global policy development to district-level programme implementation. Mixing of methods increased in relevance and rigour over time as we learned to build multiple methods into increasingly tailored evaluation questions. Evaluation teams in country-based research institutes increasingly strengthened their level of embeddedness with immunization programmes as the emphasis shifted over time to focus more heavily on the use of findings for programme learning and adaptation. Based on our experiences implementing this approach, we recommend it for the evaluation of other complex interventions, health programmes or development assistance.
Implementation research and human-centred design: how theory driven human-centred design can sustain trust in complex health systems, support measurement and drive sustained community health volunteer engagement
Authors: Adam Mary B , Minyenya-Njuguna Joy , Karuri Kamiru Wilson , Mbugua Simon , Makobu Naomi Wambui , Donelson Angela J
Published: September 2020

Human-centred design (HCD) can support complex health system interventions by navigating thorny implementation problems that often derail population health efforts. HCD is a pragmatic, ‘practice framework’, not an intervention protocol. It can build empathy by bringing patient voice, user perspective and innovation to construct and repair pieces of the intervention or health system. However, its emphasis on product development and process change with fixed end points has left it as an approach lacking explanatory power and reproducible measurement. Yet when informed by theory, the tremendous innovation potential of HCD can be harnessed to drive sustainability, mediate implementation problems, frame measurement constructs and ultimately improve population-level health outcomes. In attempting to mine, the potential of HCD we move beyond the pragmatic ‘how it works’, to the theoretical question, ‘why it works’. In doing so, we explore a more fundamental human question, ‘How can participation and engagement be sustained for impact in close to the community health systems?’ In this exploration, we illustrate the power of HCD by linking it to our theory of trust building. The research method we utilize is that of a longitudinal process evaluation. We leverage the heterogeneity of five community health units from the diverse setting (rural, peri-urban slum) to better understand what works for whom and in what context by tracking 21 groups of community health volunteers (CHVs) over 12 months. We report results with a focus on the outlier case failure to illustrate the contrast with common features of sustained CHV engagement, where recurrent reciprocal cycles of trust building are demonstrated in the successful implementation of action plans in plan-do-study-act cycles for improvement. All was accomplished by CHVs with no external funding. We conclude by discussing how HCD could be unleashed if linked to theoretical frameworks, increasing ability to address implementation challenges in complex health systems.
Evaluating an intervention for neural tube defects in coal mining cites in China: a temporal and spatial analysis
Authors: Zhang Ningxu , Liao Yilan , Ren Zhoupeng
Published: September 2020

Background

Neural tube defects (NTDs) are congenital birth defects of the central nervous system that affect 0.5–2 per 1000 pregnancies worldwide. Therefore effective interventions for birth defects, especially NTDs, are very important.

Methods

Yuanping City is a coal mining city in Shanxi Province, China, with a high incidence of NTDs. This study evaluates the effects of NTD interventions in this city after adjusting for covariates that characterize the native environment. The number of NTD cases and births for the 18 towns in Yuanping City from 2007 to 2014 were included in the study. A shared-component zero-inflated Poisson regression was applied to analyse the temporal–spatial variance among the incidence rates of NTDs in Yuanping City before and after the interventions.

Results

The results showed that existing interventions to mitigate birth defects, such as folic acid supplementation, reduced the incidence of NTDs by 53.5% in coal mining areas in Yuanping City. However, the NTD risk in areas near coal mines, especially unrestored coal mines, was still high, even after the intervention.

Conclusions

The government should focus on health hazards related to mining and agricultural production and should provide education and resources to reduce environmental exposure. Reducing environmental risks should be regarded as an early intervention strategy to mitigate birth defects.
Frontiers in human factors: embedding specialists in multi-disciplinary efforts to improve healthcare
Authors: Catchpole Ken , Bowie Paul , Fouquet Sarah , Rivera Joy , Hignett Sue
Published: September 2020

Despite the application of a huge range of human factors (HF) principles in a growing range of care contexts, there is much more that could be done to realize this expertise for patient benefit, staff well-being and organizational performance. Healthcare has struggled to embrace system safety approaches, misapplied or misinterpreted others, and has stuck to a range of outdated and potentially counter-productive myths even has safety science has developed. One consequence of these persistent misunderstandings is that few opportunities exist in clinical settings for qualified HF professionals. Instead, HF has been applied by clinicians and others, to highly variable degrees—sometimes great success, but frequently in limited and sometimes counter-productive ways. Meanwhile, HF professionals have struggled to make a meaningful impact on frontline care and have had little career structure or support. However, in the last few years, embedded clinical HF practitioners have begun to have considerable success that are now being supported and amplified by professional networks. The recent coronavirus disease of 2019 (COVID-19) experiences confirm this. Closer collaboration between healthcare and HF professionals will result in significant and ultimately beneficial changes to both professions and clinical care.
LC–QTOF-MS Presumptive Identification of Synthetic Cannabinoids without Reference Chromatographic Retention/Mass Spectral Information. I. Reversed-Phase Retention Time QSPR Prediction as an Aid to Identification of New/Unknown Compounds
Authors: Polettini Aldo E , Kutzler Johannes , Sauer Christoph , Bleicher Sergej , Schultis Wolfgang
Published: September 2020

The application of Quantitative Structure–Property Relationship (QSPR) modeling to the prediction of reversed-phase liquid chromatography retention behavior of synthetic cannabinoids (SC), and its use in aiding the untargeted identification of unknown SC are described in this paper. 1D, 2D molecular descriptors and fingerprints of 105 SC were calculated with PaDEL-Descriptor, selected with Boruta algorithm in R environment, and used to build-up a multiple linear regression model able to predict retention times, relative to JWH-018 N-pentanoic acid-d5 as internal standard, under the following conditions: Agilent ZORBAX Eclipse Plus C18 (100 mm × 2.1 mm I.D., 1.8 μm) column with Phenomenex SecurityGuard Ultra cartridge (C18, 10 mm × 2.1 mm I.D., < 2 μm) kept at 50°C; gradient elution with 5-mM ammonium formate buffer (pH 4 with formic acid) and acetonitrile with 0.01% formic acid, flow rate 0.5 mL/min. The model was validated by repeated k-fold cross-validation using two-thirds of the compounds as training set and one-third as test set (Q2 0.8593; root mean squared error, 0.087, ca. 0.56 min; mean absolute error, 0.060) and by predicting relative Retention Times (rRT) of 5 SC left completely out of the modeling study. Application of the model in routine work showed its capacity to discriminate isomers, to identify unexpected SC in combination with mass spectral information, and to reduce the length of the list of candidate isomers to ca. one-third, thus reducing significantly the time required for predicting high-resolution product ion spectra to be compared to the unknown using a computational Mass Spectrometry (MS) search/identification approach.
The Value of Not Knowing: Partisan Cue-Taking and Belief Updating of the Uninformed, the Ambiguous, and the Misinformed
Authors: Li Jianing , Wagner Michael W
Published: September 2020

The problem of a misinformed citizenry is often used to motivate research on misinformation and its corrections. However, researchers know little about how differences in informedness affect how well corrective information helps individuals develop knowledge about current events. We introduce a Differential Informedness Model that distinguishes between three types of individuals, that is, the uninformed, the ambiguous, and the misinformed, and establish their differences with two experiments incorporating multiple partisan cues and issues. Contrary to the common impression, the U.S. public is largely uninformed rather than misinformed of a wide range of factual claims verified by journalists. Importantly, we find that the success of belief updating after exposure to corrective information (via a fact-checking article) is dependent on the presence, the certainty, and the accuracy of one’s prior belief. Uninformed individuals are more likely to update their beliefs than misinformed individuals after exposure to corrective information. Interestingly, the ambiguous individuals, regardless of whether their uncertain guesses were correct, do not differ from uninformed individuals with respect to belief updating.
Extending the Breakthrough Listen nearby star survey to other stellar objects in the field
Authors: Wlodarczyk-Sroka B S , Garrett M A , Siemion A P V
Published: September 2020

We extend the source sample recently observed by the Breakthrough Listen (BL) Initiative by including additional stars (with parallaxes measured by Gaia) that also reside within the full width at half-maximum of the Green Bank 100-m Telescope and Parkes radio telescope target fields. These stars have estimated distances as listed in the extensions of the Gaia DR2 catalogue. Enlarging the sample from 1327 to 288 315 stellar objects permits us to achieve substantially better Continuous Waveform Transmitter Rate Figures of Merit (CWTFM) than any previous analysis, and allows us to place the tightest limits yet on the prevalence of nearby high-duty-cycle extraterrestrial transmitters. The results suggest ≲0.0660$^{+0.0004}_{-0.0003}$ per cent of stellar systems within 50 pc host such transmitters (assuming an EIRP ≳ 1013 W) and ≲0.039$^{+0.004}_{-0.008}$ per cent within 200 pc (assuming an EIRP ≳ 2.5 × 1014 W). We further extend our analysis to much greater distances, though we caution that the detection of narrow-band signals beyond a few hundred pc may be affected by interstellar scintillation. The extended sample also permits us to place new constraints on the prevalence of extraterrestrial transmitters by stellar type and spectral class. Our results suggest targeted analyses of Search for Extraterrestrial Intelligence radio data can benefit from taking into account the fact that in addition to the target at the field centre, many other cosmic objects reside within the primary beam response of a parabolic radio telescope. These include foreground and background Galactic stars, but also extragalactic systems. With distances measured by Gaia, these additional sources can be used to place improved limits on the prevalence of extraterrestrial transmitters, and extend the analysis to a wide range of cosmic objects.
Revisiting 3D chromatin architecture in cancer development and progression
Authors: Feng Yuliang , Pauklin Siim
Published: September 2020

Cancer development and progression are demarcated by transcriptional dysregulation, which is largely attributed to aberrant chromatin architecture. Recent transformative technologies have enabled researchers to examine the genome organization at an unprecedented dimension and precision. In particular, increasing evidence supports the essential roles of 3D chromatin architecture in transcriptional homeostasis and proposes its alterations as prominent causes of human cancer. In this article, we will discuss the recent findings on enhancers, enhancer–promoter interaction, chromatin topology, phase separation and explore their potential mechanisms in shaping transcriptional dysregulation in cancer progression. In addition, we will propose our views on how to employ state-of-the-art technologies to decode the unanswered questions in this field. Overall, this article motivates the study of 3D chromatin architecture in cancer, which allows for a better understanding of its pathogenesis and develop novel approaches for diagnosis and treatment of cancer.
Diversity and evolution of B-family DNA polymerases
Authors: Kazlauskas Darius , Krupovic Mart , Guglielmini Julien , Forterre Patrick , Venclovas Česlovas
Published: September 2020

B-family DNA polymerases (PolBs) represent the most common replicases. PolB enzymes that require RNA (or DNA) primed templates for DNA synthesis are found in all domains of life and many DNA viruses. Despite extensive research on PolBs, their origins and evolution remain enigmatic. Massive accumulation of new genomic and metagenomic data from diverse habitats as well as availability of new structural information prompted us to conduct a comprehensive analysis of the PolB sequences, structures, domain organizations, taxonomic distribution and co-occurrence in genomes. Based on phylogenetic analysis, we identified a new, widespread group of bacterial PolBs that are more closely related to the catalytically active N-terminal half of the eukaryotic PolEpsilon (PolEpsilonN) than to Escherichia coli Pol II. In Archaea, we characterized six new groups of PolBs. Two of them show close relationships with eukaryotic PolBs, the first one with PolEpsilonN, and the second one with PolAlpha, PolDelta and PolZeta. In addition, structure comparisons suggested common origin of the catalytically inactive C-terminal half of PolEpsilon (PolEpsilonC) and PolAlpha. Finally, in certain archaeal PolBs we discovered C-terminal Zn-binding domains closely related to those of PolAlpha and PolEpsilonC. Collectively, the obtained results allowed us to propose a scenario for the evolution of eukaryotic PolBs.
CMNPD: a comprehensive marine natural products database towards facilitating drug discovery from the ocean
Authors: Lyu Chuanyu , Chen Tong , Qiang Bo , Liu Ningfeng , Wang Heyu , Zhang Liangren , Liu Zhenming
Published: September 2020

Marine organisms are expected to be an important source of inspiration for drug discovery after terrestrial plants and microorganisms. Despite the remarkable progress in the field of marine natural products (MNPs) chemistry, there are only a few open access databases dedicated to MNPs research. To meet the growing demand for mining and sharing for MNPs-related data resources, we developed CMNPD, a comprehensive marine natural products database based on manually curated data. CMNPD currently contains more than 31 000 chemical entities with various physicochemical and pharmacokinetic properties, standardized biological activity data, systematic taxonomy and geographical distribution of source organisms, and detailed literature citations. It is an integrated platform for structure dereplication (assessment of novelty) of (marine) natural products, discovery of lead compounds, data mining of structure-activity relationships and investigation of chemical ecology. Access is available through a user-friendly web interface at https://www.cmnpd.org. We are committed to providing a free data sharing platform for not only professional MNPs researchers but also the broader scientific community to facilitate drug discovery from the ocean.
Unbiased investigation of specificities of prime editing systems in human cells
Authors: Kim Do Yon , Moon Su Bin , Ko Jeong-Heon , Kim Yong-Sam , Kim Daesik
Published: September 2020

Prime editors (PEs) enable targeted precise editing, including the generation of substitutions, insertions and deletions, in eukaryotic genomes. However, their genome-wide specificity has not been explored. Here, we developed Nickase-based Digenome-seq (nDigenome-seq), an in vitro assay that uses whole-genome sequencing to identify single-strand breaks induced by CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) nickase. We used nDigenome-seq to screen for potential genome-wide off-target sites of Cas9 H840A nickase, a PE component, targeted to nine human genomic sites. Then, using targeted amplicon sequencing of off-target candidates identified by nDigenome-seq, we showed that only five off-target sites showed detectable PE-induced modifications in cells, at frequencies ranging from 0.1 to 1.9%, suggesting that PEs provide a highly specific method of precise genome editing. We also found that PE specificity in human cells could be further improved by incorporating mutations from engineered Cas9 variants, particularly eSpCas9 and Sniper Cas9, into PE.
Clinical Pearls and Methods for Intraoperative Awake Language Mapping
Authors: Morshed Ramin A , Young Jacob S , Lee Anthony T , Berger Mitchel S , Hervey-Jumper Shawn L
Published: September 2020

Intraoperative language mapping of tumor and peritumor tissue is a well-established technique for avoiding permanent neurological deficits and maximizing extent of resection. Although there are several components of language that may be tested intraoperatively (eg, naming, writing, reading, and repetition), there is a lack of consistency in how patients are tested intraoperatively as well as the techniques involved to ensure safety during an awake procedure. Here, we review appropriate patient selection, neuroanesthetic techniques, cortical and subcortical language mapping stimulation paradigms, and selection of intraoperative language tasks used during awake craniotomies. We also expand on existing language mapping reviews by considering how intensity and timing of electrical stimulation may impact interpretation of mapping results.
Localization of three-dimensional $\mathcal{N}=2$ supersymmetric theories on $S^1 \times D^2$
Authors: Yoshida Yutaka , Sugiyama Katsuyuki
Published: September 2020

We study three-dimensional $\mathcal{N}=2$ supersymmetric Chern—Simons matter theories on the direct product of a circle and a two-dimensional hemisphere ($S^1 \times {D^2}$) with specified boundary conditions by the method of localization. We construct boundary interactions to cancel the supersymmetric variation of the three-dimensional superpotential term and the Chern—Simons term and show inflows of the bulk—boundary anomalies. We find that the boundary conditions induce two-dimensional $\mathcal{N}=(0,2)$-type supersymmetry on the boundary torus. We also study the relation between the three-dimensional—two-dimensional coupled partition function of our model and three-dimensional holomorphic blocks.
Change over time in adolescent smoking, cannabis use and their association: findings from the School Health Research Network in Wales
Authors: Page N , Hallingberg B , Brown R , Lowthian E , Hewitt G , Murphy S , Moore G
Published: September 2020

Background

While tobacco smoking has declined among UK youth in recent decades, cannabis use has begun to show some growth. Given their interrelationship, growth in cannabis use may act as a barrier to continued reduction in youth smoking. This paper assesses recent tobacco and cannabis use trends in Wales, and their association, to explore whether change in cannabis use might have impacted youth tobacco smoking prevalence.

Methods

Repeat cross-sectional data on tobacco and cannabis use were obtained from biennial Welsh Student Health and Wellbeing surveys between 2013 and 2019. Data were pooled and analysed using logistic regression with adjustment for school-level clustering.

Results

No change in regular youth tobacco smoking was observed between 2013 and 2019. In contrast, current cannabis use increased during this time, and cannabis users had significantly greater odds of regular tobacco smoking. After adjusting for change in cannabis use, a significant decline in youth tobacco smoking was observed (OR 0.95; 95% confidence intervals: 0.92, 0.97).

Conclusion

Recent growth in cannabis use among young people in Wales may have offset prospective declines in regular tobacco smoking. Further reductions in youth smoking may require more integrated policy approaches to address the co-use of tobacco and cannabis among adolescents.
From collaborative to institutional reflexivity: Calibrating responsibility in the funding process
Authors: Grimpe Barbara , Stahl Bernd Carsten , Ten Holter Carolyn , Inglesant Philip , Eden Grace , Patel Menisha , Jirotka Marina
Published: September 2020

Science–policy organisations are expected to be reflexive of their political influence on research and society. In this long-standing discourse on institutional reflexivity, formal organisations have largely been considered as a whole, and from a structural, or systemic perspective, whereas much less is known about everyday organisational practices; how individual organisational members reflect on and act upon their own as well as their organisation’s limits of knowledge and pre-commitments, if at all. We address this gap through an analysis of qualitative interviews with one national funding institution’s staff overseeing funding for research into information and communication technologies. We develop a bridging concept between individual and institutional reflexivity, which we call ‘collaborative reflexivity’. Through collaborative reflexive processes, individual employees contribute to the entire organisation’s institutional reflexivity. Our findings help to better understand ‘responsible’ behaviour in funding processes, as part of the growing international movement of Responsible Research and Innovation.
Screening Sweetpotato Genotypes for Resistance to a North Carolina Isolate of Meloidogyne enterolobii
Authors: Schwarz Tanner R. , Li Chunying , Yencho G. Craig , Pecota Kenneth V. , Heim Chris R. , Davis Eric L.
Published: September 2020

Potential resistance to the guava root-knot nematode, Meloidogyne enterolobii, in 91 selected sweetpotato (Ipomoea batatas [L.] Lam.) genotypes was evaluated in six greenhouse experiments. Ten thousand eggs of M. enterolobii were inoculated on each sweetpotato genotype grown in a 3:1 sand to soil mixture. Sixty days after inoculation, the percentage of total roots with nematode-induced galls was determined, and nematode eggs were extracted from roots. Significant differences (P < 0.001) between sweetpotato genotypes were found in all six tests for gall rating, total eggs, and eggs per gram of root. Resistant sweetpotato genotypes were calculated as final eggs per root system divided by the initial inoculum, where Pf/Pi < 1 (reproduction factor; final egg count divided by initial inoculum of 10,000 eggs), and statistical mean separations were confirmed by Fisher’s least significant difference t test. Our results indicated that 19 out of 91 tested sweetpotato genotypes were resistant to M. enterolobii. Some of the susceptible genotypes included ‘Covington,’ ‘Beauregard,’ ‘NCDM04-001’, and ‘Hernandez.’ Some of the resistant sweetpotato genotypes included ‘Tanzania,’ ‘Murasaki-29,’ ‘Bwanjule,’ ‘Dimbuka-Bukulula,’ ‘Jewel,’ and ‘Centennial.’ Most of the 19 resistant sweetpotato genotypes supported almost no M. enterolobii reproduction, with <20 eggs/g root of M. enterolobii. A number of segregants from a ‘Tanzania’ × ‘Beauregard’ cross demonstrated strong resistance to M. enterolobii observed in the ‘Tanzania’ parent. In collaboration with North Carolina State University sweetpotato breeding program, several genotypes evaluated in these tests are being used to incorporate the observed resistance to M. enterolobii into commercial sweetpotato cultivars.
Predictors of Childhood Injury in Children Reported to Child Protective Services
Authors: Barczyk Amanda N. , Jones Kristian , Duzinski Sarah V. , Lawson Karla A.
Published: September 2020

Background:

Adverse childhood experiences, such as child maltreatment, have been shown to result in negative health outcomes throughout an individual's life. Previous research has found that children with a prior allegation of maltreatment die due to unintentional injuries at twice the rate of children who were not reported to Child Protective Services, however, death is only one outcome of injury and many unintentional injuries do not result in death.

Methods:

This secondary analysis of Longitudinal Studies of Child Abuse and Neglect (LONGSCAN) data examined predictors of injury in children whose family has been reported to CPS utilizing the ecological-developmental framework theoretical domains which guided LONGSCAN: child characteristics, family/caregiver characteristics, parental and family functioning, extrafamilial relationship skills, community ecology, child outcomes, and systems of care factors.

Results:

Logistic regression modeling showed that the likelihood of childhood injury significantly increased for those children who did not recognize or appropriately respond to cues of ending a conversation (OR=.37), caregiver reported child always has a good place to play in their neighborhood (OR=1.57), and child utilized educational services (OR=2.06).

Conclusion:

Understanding the predictors of injury is necessary to implement injury prevention interventions targeting the unique needs of this vulnerable population and increase awareness of prevention strategies to reduce childhood injuries.
A total facility approach to reducing HIV stigma in health facilities: implementation process and lessons learned
Authors: Nyblade Laura , Mbuya-Brown Rebecca J. , Ezekiel Mangi J. , Addo Nii A. , Sabasaba Amon N. , Atuahene Kyeremeh , Kiwia Pfiraeli , Gyamera Emma , Akyoo Winfrida O. , Vormawor Richard , Manyama Willbrord , Shoko Subira , Mingkwan Pia , Stewart Christin , Balampama Marianna , Bowsky Sara , Jacinthe Suzie , Alsoufi Nabil , Kraemer John D.
Published: September 2020

Objectives:

To describe development and implementation of a three-stage ‘total facility’ approach to reducing health facility HIV stigma in Ghana and Tanzania, to facilitate replication.

Design:

HIV stigma in healthcare settings hinders the HIV response and can occur during any interaction between client and staff, between staff, and within institutional processes and structures. Therefore, the design focuses on multiple socioecological levels within a health facility and targets all levels of staff (clinical and nonclinical).

Methods:

The approach is grounded in social cognitive theory principles and interpersonal or intergroup contact theory that works to combat stigma by creating space for interpersonal interactions, fostering empathy, and building efficacy for stigma reduction through awareness, skills, and knowledge building as well as through joint action planning for changes needed in the facility environment. The approach targets actionable drivers of stigma among health facility staff: fear of HIV transmission, awareness of stigma, attitudes, and health facility environment.

Results:

The results are the three-stage process of formative research, capacity building, and integration into facility structures and processes. Key implementation lessons learned included the importance of formative data to catalyze action and shape intervention activities, using participatory training methodologies, involving facility management throughout, having staff, and clients living with HIV facilitate trainings, involving a substantial proportion of staff, mixing staff cadres and departments in training groups, and integrating stigma-reduction into existing structures and processes.

Conclusion:

Addressing stigma in health facilities is critical and this approach offers a feasible, well accepted method of doing so.
Integration and scale-up of efforts to measure and reduce HIV-related stigma: the experience of Thailand
Authors: Siraprapasiri Taweesap , Srithanaviboonchai Kriengkrai , Chantcharas Parichart , Suwanphatthana Niwat , Ongwandee Sumet , Khemngern Porntip , Benjarattanaporn Patchara , Mingkwan Pia , Nyblade Laura
Published: September 2020

Objective(s):

To share Thailand's journey to develop and implement a national response to measure and tackle HIV-related stigma and discrimination and key implementation lessons learned.

Design:

A national response to stigma and discrimination including policy, measurement, and interventions. Intervention activities began in health facilities because of their key role in achieving health outcomes.

Methods:

Three building blocks were implemented: policy and its translation into a roadmap for action; measurement development and routinization to inform intervention design and track progress; and intervention development and implementation.

Results:

Thailand has successfully integrated a response to stigma and discrimination into its national HIV response. Stigma and discrimination-reduction was included as a key strategic goal for the first time in the 2014–2016 National AIDS Strategic Plan. A costed national stigma and discrimination-reduction roadmap incorporated into the operational plan provided clear strategic direction on how to move forward. The development of HIV-related stigma and discrimination measures and their incorporation into the national HIV monitoring and evaluation framework has led to routine data collection to monitor stigma and discrimination in health facilities, key populations, and the general population. Development and successful piloting of a health facility stigma-reduction package – the 3 × 4 approach – has led to national scale-up of the approach through a modified approach. Thailand continues to evolve and innovate the program, including developing new activities to tackle stigma and discrimination beyond the health system.

Conclusion:

Thailand's experience demonstrates the key elements needed to make addressing stigma and discrimination a priority in the national HIV response.
Intersectional stigmas and HIV-related outcomes among a cohort of key populations enrolled in stigma mitigation interventions in Senegal
Authors: Lyons Carrie E. , Olawore Oluwasolape , Turpin Gnilane , Coly Karleen , Ketende Sosthenes , Liestman Benjamin , Ba Ibrahima , Drame Fatou M. , Ndour Cheikh , Turpin Nguissali , Ndiaye Sidy M. , Mboup Souleymane , Toure-Kane Coumba , Leye-Diouf Nafissatou , Castor Delivette , Diouf Daouda , Baral Stefan D.
Published: September 2020

Objectives:

The current study aims to assess longitudinal differences in stigma and HIV outcomes among key populations at risk for and living with HIV.

Design:

Key populations enrolled into two parallel prospective cohorts; one for female sex workers and one for sexual and gender minorities (SGMs). Participants were recruited from three urban areas in Senegal; were followed for 24 months; and had the option to participate in an integrated stigma mitigation intervention.

Methods:

Participants included individuals both at risk for and living with HIV. Sociobehavioral questionnaires and biological HIV testing were administered every 3–4 months. Longitudinal analyses used nonparametric Chi-squared test for trends and multivariable logistic regression with generalized estimating equations.

Results:

183 SGM and 192 sex workers were enrolled. Among SGM participants, 39.9% were living with HIV at baseline and incidence over 24 months was 3.21/100 person-years. Among sex workers, 36.6% were living with HIV at baseline and incidence was 1.32/100 person-years. Among SGM, perceived healthcare stigma (P < 0.001), anticipated healthcare stigma (P < 0.001), and perceived friend stigma (P = 0.047) reduced, but differed by HIV status for perceived [adjusted odds ratio (aOR): 3.51; 95% confidence interval (CI): 1.75, 7.06] and anticipated healthcare stigmas (aOR: 2.85; 95% CI: 1.06–7.67). Among sex workers perceived healthcare stigma (P = 0.043) and perceived friend stigma (P = 0.006) reduced. Viral suppression increased among SGM (P = 0.028) and was associated with perceived (aOR: 2.87; 95% CI: 1.39–5.55) and enacted healthcare stigma (aOR: 0.42; 95% CI: 0.18–0.99).

Conclusion:

Overall, there were decreases in stigmas observed but clear differences in stigma patterns by HIV status. These data highlight the need to consider specific strategies to address multiple intersecting stigmas as a means of improving HIV-related prevention and treatment outcomes among key populations with diverse identities.
Double Trouble
Authors: Wang Sherry S. , Revels Jonathan , Dubinsky Theodore J.
Published: September 2020

With the increasing rate of twin pregnancies due to increase in maternal age and use of assisted reproduction, it is important to be aware of unique diseases which occur specifically to twin pregnancies, especially in monochorionic twin pregnancies. These entities include twin to twin transfusion syndrome, twin anemia polycythemia sequence, twin reversed arterial perfusion, cotwin demise, and conjoined twins. Early evaluation and documentation are imperative to guide management which ultimately leads to better patient outcomes.
Status Epilepticus in Children
Authors: Zimmern Vincent , Korff Christian
Published: September 2020

For various reasons, status epilepticus in children is different than in adults. Pediatric specificities include status epilepticus epidemiology, underlying etiologies, pathophysiological mechanisms, and treatment options. Relevant data from the literature are presented for each of them, and questions remaining open for future studies on status epilepticus in childhood are listed.
Markers in Status Epilepticus Prognosis
Authors: Alkhachroum Ayham , Der-Nigoghossian Caroline A. , Rubinos Clio , Claassen Jan
Published: September 2020

Status epilepticus (SE) is a neurologic emergency with high morbidity and mortality. The assessment of a patient's prognosis is crucial in making treatment decisions. In this review, we discuss various markers that have been used to prognosticate SE in terms of recurrence, mortality, and functional outcome. These markers include demographic, clinical, electrophysiological, biochemical, and structural data. The heterogeneity of SE etiology and semiology renders development of prognostic markers challenging. Currently, prognostication in SE is limited to a few clinical scores. Future research should integrate clinical, genetic and epigenetic, metabolic, inflammatory, and structural biomarkers into prognostication models to approach “personalized medicine” in prognostication of outcomes after SE.
Stability of Extemporaneously Prepared Preservative-Free Methylphenidate 5 mg/mL Intravenous Solution
Authors: Barra Megan E. , Edlow Brian L. , Lund James T. , Sencion Katherine , Vetrano John , Reilly-Tremblay Cherylann , Zhang Edlyn R. , Bodien Yelena , Brown Emery N. , Solt Ken
Published: September 2020

Purpose

To advance the implementation of consciousness-promoting therapies in patients with acute disorders of consciousness, the availability of potential therapeutic agents in formulations suitable for administration in hospitalized patients in the presence of complex comorbid conditions is paramount. The purpose of this study is to evaluate the long-term stability of extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution.

Methods

A methylphenidate 5 mg/mL solution was prepared under proper aseptic techniques with Methylphenidate HCl USP powder mixed in sterile water for solution. Methylphenidate HCl 5 mg/ml solution was sterilized by filtration technique under USP <797> compliant conditions. Samples were stored refrigerated (2 - 8°C) and analyzed at approximately day 1, 30, 60, 90, 180, and 365. At each time point, chemical and physical stability was evaluated by visual inspection, pH measurement, membrane filtration procedure, turbidometric or photometric technique, and high-performance liquid chromatography (HPLC) analysis.

Results

Over the 1-year study period, the sample retained 96.76 – 102.04% of initial methylphenidate concentration. There was no significant change in the visual appearance, pH level or particulate matter during the study period. The sample maintained bacterial and fungi sterility, and endotoxin levels were undetectable throughout the 1-year stability period.

Conclusions

Extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution was physically and chemically stable for up to 365 days when stored in amber glass vials at refrigerated temperatures (2 - 8°C).
Oxycodone self-administration activates the mitogen-activated protein kinase/mitogen- and stress-activated protein kinase (MAPK-MSK) signaling pathway in the rat dorsal striatum
Authors: Blackwood Christopher A. , McCoy Michael T. , Ladenheim Bruce , Cadet Jean Lud
Published: September 2020

To identify signaling pathways activated by oxycodone self-administration (SA), Sprague-Dawley rats self-administered oxycodone for 20 days using short-access (ShA, 3 h) and long-access (LgA, 9 h) paradigms. Animals were euthanized two hours after SA cessation and dorsal striata were used in post-mortem molecular analyses. LgA rats escalated their oxycodone intake and separated into lower (LgA-L) or higher (LgA-H) oxycodone takers. LgA-H rats showed increased striatal protein phosphorylation of ERK1/2 and MSK1/2. Histone H3, phosphorylated at serine 10 and acetylated at lysine 14 (H3S10pK14Ac), a MSK1/2 target, showed increased abundance only in LgA-H rats. RT-qPCR analyses revealed increased AMPA receptor subunits,GluA2andGluA3mRNAs in the LgA-H rats.GluA3, but notGluA2, expression correlated positively with changes in pMSK1/2 and H3S10pK14Ac. Our findings indicate that escalated oxycodone SA results in MSK1/2-dependent histone phosphorylation, which promoted increases in striatal gene expression. Our observations offer novel avenues for pharmacological interventions against oxycodone addiction.
Rapid “mix and read” assay for scalable detection of SARS-CoV-2 antibodies in patient plasma
Authors: Yue Hong , Nowak Radosław P. , Overwijn Daan , Payne N. Connor , Fischinger Stephanie , Atyeo Caroline , Baden Lindsey R. , Nilles Eric J. , Karlson Elizabeth W. , Yu Xu G. , Li Jonathan Z. , Alter Galit , Mazitschek Ralph , Fischer Eric S.
Published: September 2020

The human beta coronavirus SARS-CoV-2, causative virus of COVID-19, has infected more than 15 million people globally and continues to spread. Widespread, population level testing to detect active and past infections is critical to curb the COVID-19 pandemic. Antibody (serological) testing is the only option for detecting past infections outside the narrow window accessible to nucleic acid-based tests. However, currently available serological assays commonly lack scalability. Here, we describe the development of a rapid homogenous serological assay for the detection of antibodies to SARS-CoV-2 in patient plasma. We show that the fluorescence-based assay accurately detects seroconversion in COVID-19 patients from less than 1μL of plasma. Using a cohort of samples from COVID-19 infected or healthy individuals, we demonstrate detection with 100% sensitivity and specificity. This assay addresses an important need for a robust, low barrier to implementation, and scalable serological assay with complementary strengths to currently available serological platforms.
The clinical course of COVID-19 in the outpatient setting: a prospective cohort study
Authors: Blair Paul W. , Brown Diane , Jang Minyoung , Antar Annukka A.R. , Keruly Jeanne C. , Bachu Vismaya S. , Townsend Jennifer L. , Tornheim Jeffrey , Keller Sara C. , Sauer Lauren , Thomas David L. , Manabe Yukari C.
Published: September 2020

Background

Outpatient COVID-19 has been insufficiently characterized.

Objective

To determine the progression of disease and subsequent determinants of hospitalization.

Design

A prospective outpatient cohort.

Setting

Outpatients were recruited by phone between April 21 to June 23, 2020 after receiving outpatient or emergency department testing within a large health network in Maryland, USA.

Participants

Outpatient adults with positive RT-PCR results for SARS-CoV-2.

Measurements

Symptoms, portable pulse oximeter oxygen saturation (SaO2), heart rate, and temperature were collected by participants on days 0, 3, 7, 14, 21, and 28 after enrollment. Baseline demographics, comorbid conditions were evaluated for risk of subsequent hospitalization using negative binomial, logistic, and random effects logistic regression.

Results

Among 118 SARS-CoV-2 infected outpatients, the median age was 56.0 years (IQR, 50.0 to 63.0) and 50 (42.4%) were male. Among those reporting active symptoms, the most common symptoms during the first week since symptom onset included weakness/fatigue (67.3%), cough (58.0%), headache (43.8%), and sore throat (34.8%). Participants returned to their usual health a median of 20 days (IQR, 13 to 38) from the symptom onset, and only 65.5% of respondents were at their usual health during the fourth week of illness. Over 28 days, 10.9% presented to the emergency department and 7.6% required hospitalization. Individuals at the same duration of illness had a 6.1 times increased adjusted odds of subsequent hospitalization per every percent decrease in home SaO2(95% confidence interval [CI]: 1.41 to 31.23, p=0.02).

Limitations

Severity and duration of illness may differ in a younger population.

Conclusion

Symptoms often persisted but uncommonly progressed to hospitalization. Home SaO2might be an important adjunctive tool to identify progression of COVID-19.

Registration

Clinicaltrials.gov NCT number:NCT04496466

Funding Source

The Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases Discovery Program and the Johns Hopkins University School of Medicine
Predicting the Progression of Mild Cognitive Impairment Using Machine Learning: A Systematic, Quantitative and Critical Review
Authors: Ansart Manon , Epelbaum Stéphane , Bassignana Giulia , Bône Alexandre , Bottani Simona , Cattai Tiziana , Couronné Raphaël , Faouzi Johann , Koval Igor , Louis Maxime , Thibeau-Sutre Elina , Wen Junhao , Wild Adam , Burgos Ninon , Dormont Didier , Colliot Olivier , Durrleman Stanley
Published: September 2020

We performed a systematic review of studies focusing on the automatic prediction of the progression of mild cognitive impairment to Alzheimer’s disease (AD) dementia, and a quantitative analysis of the methodological choices impacting performance. This review included 172 articles, from which 234 experiments were extracted. For each of them, we reported the used data set, the feature types, the algorithm type, performance and potential methodological issues. The impact of these characteristics on the performance was evaluated using a multivariate mixed effect linear regressions. We found that using cognitive, fluorodeoxyglucose-positron emission tomography or electroencephalography and magnetoencephalography variables significantly improved predictive performance compared to not including them, whereas including other modalities, in particular T1 magnetic resonance imaging, did not show a significant effect. The good performance of cognitive assessments questions the wide use of imaging for predicting the progression to AD and advocates for exploring further fine domain-specific cognitive assessments. We also identified several methodological issues, including the absence of a test set, or its use for feature selection or parameter tuning in nearly a fourth of the papers. Other issues, found in 15% of the studies, cast doubts on the relevance of the method to clinical practice. We also highlight that shortterm predictions are likely not to be better than predicting that subjects stay stable over time. These issues highlight the importance of adhering to good practices for the use of machine learning as a decision support system for the clinical practice.