bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre-exposure prophylaxis rollout in a national public sector program: the Kenyan case study
Authors: Masyuko Sarah , Mukui Irene , Njathi Olivia , Kimani Maureen , Oluoch Patricia , Wamicwe Joyce , Mutegi Jane , Njogo Susan , Anyona Micah , Muchiri Phillip , Maikweki Lucy , Musyoki Helgar , Bahati Prince , Kyongo Jordan , Marwa Tom , Irungu Elizabeth , Kiragu Michael , Kioko Urbanus , Ogando Justus , Were Dan , Bartilol Kigen , Sirengo Martin , Mugo Nelly , Baeten Jared M. , Cherutich Peter , PrEP technical working group on behalf of the
Published: November 2018

Background While advances have been made in HIV prevention and treatment, new HIV infections continue to occur. The introduction of pre-exposure prophylaxis (PrEP) as an additional HIV prevention option for those at high risk of HIV may change the landscape of the HIV epidemic, especially in sub-Saharan Africa, which bears the greatest HIV burden. Methods: This paper details Kenya’s experience of PrEP rollout as a national public sector program. The process of a national rollout of PrEP guidance, partnerships, challenges, lessons learnt and progress related to national scale up of PrEP in Kenya, as of 2018, is described. National rollout of PrEP was strongly lead by the government, and work was executed through a multidisciplinary, multi-organisation dedicated team. This required reviewing available evidence, providing guidance to health providers, integration into existing logistic and health information systems, robust communication and community engagement. Mapping of the response showed that subnational levels had existing infrastructure but required targeted resources to catalyse PrEP provision. Rollout scenarios were developed and adopted, with prioritisation of 19 counties focusing on high incidence area and high potential PrEP users to maximise impact and minimise costs. Results: PrEP is now offered in over 900 facilities countrywide. There are currently over 14000 PrEP users 1 year after launching PrEP.Conclusions: Kenya becomes the first African country to rollout PrEP as a national program, in the public sector. This case study will provide guidance for low- and middle-income countries planning the rollout of PrEP in response to both generalised and concentrated epidemics.
Phage Mu Gam protein promotes NHEJ in concert with
Escherichia coli
ligase
Authors: Bhattacharyya Sudipta , Soniat Michael M. , Walker David , Jang Sooin , Finkelstein Ilya J. , Harshey Rasika M.
Published: November 2018

The Gam protein of transposable phage Mu is an ortholog of eukaryotic and bacterial Ku proteins, which carry out nonhomologous DNA end joining (NHEJ) with the help of dedicated ATP-dependent ligases. Many bacteria carry Gam homologs associated with either complete or defective Mu-like prophages, but the role of Gam in the life cycle of Mu or in bacteria is unknown. Here, we show that MuGam is part of a two-component bacterial NHEJ DNA repair system. Ensemble and single-molecule experiments reveal that MuGam binds to DNA ends, slows the progress of RecBCD exonuclease, promotes binding of NAD
+
-dependent
Escherichia coli
ligase A, and stimulates ligation. In vivo, Gam equally promotes both precise and imprecise joining of restriction enzyme-digested linear plasmid DNA, as well as of a double-strand break (DSB) at an engineered I-
Sce
I site in the chromosome. Cell survival after the induced DSB is specific to the stationary phase. In long-term growth competition experiments, particularly upon treatment with a clastogen, the presence of
gam
in a Mu lysogen confers a distinct fitness advantage. We also show that the role of Gam in the life of phage Mu is related not to transposition but to protection of genomic Mu copies from RecBCD when viral DNA packaging begins. Taken together, our data show that MuGam provides bacteria with an NHEJ system and suggest that the resulting fitness advantage is a reason that bacteria continue to retain the
gam
gene in the absence of an intact prophage.
Differential argument marking and object movement in Old Japanese
Authors: Yanagida Yuko
Published: November 2018

This paper discusses object movement and its diachronic source in what Yanagida and Whitman (2009) (Y&W) label nominalized clauses in Old Japanese (OJ; 8 century). When the subject is marked by genitive ga, the ancestor of Modern Japanese nominative, the object necessarily moves over the subject, resulting in OSV. Y&W argue that OJ ga is licensed by agentive v and that OSV word order is a property of active alignment. From both theoretical and typological perspectives, this paper argues that case marking and word order variations in OJ are best analyzed as instances of the typologically well attested phenomenon of Differential Argument Marking (DAM). It is shown that object movement is a widely attested subtype of DAM. This paper proposes that the so-called Subject-in-Situ Generalization (SSG) (Alexiadou and Anagnostopoulou 2001) provides a unified analysis of object movement across languages.
The acquisition of Spanish passives: The Comparison Between Subject Experiencer Versus Actional Verbs and Direct Aspectual Semantic Evidence for the Adjectival Interpretation
Authors: Oliva Jesús , Wexler Kenneth
Published: November 2018

We test the maturational/adjectival analysis theory of development of passives in Spanish. Children perform less well on psychological passives than on actional passives. Since Borer and Wexler (1987), the most prominent hypothesis is that this difference is due to children’s use of an adjectival interpretation of passives. Spanish passives are aux + participle, with different auxiliaries for verbal/adjectival. In Experiment 1, children perform better on actional than on psychological passives. Experiment 2, using the method of Gavarró and Parramon (2017), tests the eventive/stative interpretation of passives directly. As predicted, children often recover an incorrect stative interpretation for verbal passives. Strikingly, the non-commonsensical prediction of the theory that there is a negative correlation between adult-like performance in the theta-role and aspect experiments is confirmed.
Sentence repetition and language impairment in French-speaking children with ASD
Authors: Silleresi Silvia , Tuller Laurie , Delage Hélène , Durrleman Stephanie , Bonnet-Brilhault Frédérique , Malvy Joëlle , Prévost Philippe
Published: November 2018

This study investigates formal language abilities in French-speaking children with Autism Spectrum Disorder (ASD). We report on the usefulness of the LITMUS-Sentence-Repetition-French task in distinguishing children with impaired language (ASD-LI) from children with normal language (ASD-LN). We examined complexity of syntactic computation, to determine whether children with ASD-LI behave analogously to children with SLI. Results showed that the ASD-LI group performed like the SLI group, while the ASD-LN group performed like the TD group. Despite the existence of a link between nonverbal IQ (NVIQ) and performance on SR, this correlation was not linear, due to the presence of children with each of the four formal language ability/NVIQ profiles, indicating the possible independence of formal language from nonverbal intelligence.
Microstructure and tensile properties of a 0.20C–4.86Mn steel after short intercritical-annealing times
Authors: Li Yan , Huyan Fei , Ding Wei
Published: November 2018

This work studies the microstructure and tensile properties of a cold-rolled Fe–0.20C–4.86Mn (mass %) steel after short intercritical annealing (IA) times using scanning and transmission electron microscopy, and uniaxial tensile tests. The short IA time is applied to represent the process characteristics of the industrial continuous annealing line. The experimental results show that IA temperature has a strong influence on the final microstructure and tensile properties while IA time has less. The fractions of retained austenite are much higher after IA at 650 and 675°C than the other IA temperatures, and thus improving elongation. Simulations using the DICTRA software and constitutive modelling are further performed to assist the understanding of the microstructure evolution and stress–strain curves.
CCQM-K120 (Carbon dioxide at background and urban level)
Authors: Flores Edgar , Viallon Joële , Choteau Tiphaine , Moussay Philippe , Idrees Faraz , Wielgosz Robert I , Lee Jeongsoon , Zalewska Ewelina , Nieuwenkamp Gerard , Veen Adriaan van der , Konopelko L A , Kustikov Y A , Kolobova A V , Chubchenko Y K , Efremova O V , Zhe BI , Zhou Zeyi , Zhou Zeyi , Rhoderick George C , Hodge Joseph T , Shimosaka Takuya , Aoki Nobuyuki , Hall Brad , Brewer Paul , Cieciora Dariusz , Sega Michela , Macé Tatiana , Fükő Judit , Nagyné Szilágyi Zsófia , Büki Tamás , Jozela Mudalo I , Ntsasa Napo G , Leshabane Nompumelelo , Tshilongo James , Johri Prabha , Tarhan Tanil
Published: November 2018

CCQM-K120.a comparison involves preparing standards of carbon dioxide in air which are fit for purpose for the atmospheric monitoring community, with stringent requirements on matrix composition and measurement uncertainty of the CO2 mole fraction. This represents an analytical challenge and is therefore considered as a Track C comparison. The comparison will underpin CMC claims for CO2 in air for standards and calibrations services for the atmospheric monitoring community, matrix matched to real air, over the mole fraction range of 250 μmol/mol to 520 μmol/mol.

CCQM-K120.b comparison tests core skills and competencies required in gravimetric preparation, analytical certification and purity analysis. It is considered as a Track A comparison. It will underpin CO2 in air and nitrogen claims in a mole fraction range starting at the smallest participant's reported expanded uncertainty and ending at 500 mmol/mol. Participants successful in this comparison may use their result in the flexible scheme and underpin claims for all core mixtures

This study has involved a comparison at the BIPM of a suite of 44 gas standards prepared by each of the participating laboratories. Fourteen laboratories took part in both comparisons (CCQM-K120.a, CCQM-K120.b) and just one solely in the CCQM-K120.b comparison.

The standards were sent to the BIPM where the comparison measurements were performed. Two measurement methods were used to compare the standards, to ensure no measurement method dependant bias: GC-FID and FTIR spectroscopic analysis corrected for isotopic variation in the CO2 gases, measured at the BIPM using absorption laser spectroscopy. Following the advice of the CCQM Gas Analysis Working Group, results from the FTIR method were used to calculate the key comparison reference values.

KEY WORDS FOR SEARCH

FTIR, CO2, GC-FID, Carbon dioxide at background level, Carbon dioxide at urban level, Delta Ray, CO2 gas standards

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Validation of electron microscopy initial models via small angle X-ray scattering curves
Authors: Jiménez Amaya , Jonic Slavica , Majtner Tomas , Otón Joaquín , Vilas Jose Luis , Maluenda David , Mota Javier , Ramírez-Aportela Erney , Martínez Marta , Rancel Yaiza , Segura Joan , Sánchez-García Ruben , Melero Roberto , del Cano Laura , Conesa Pablo , Skjaerven Lars , Marabini Roberto , Carazo Jose M , Sorzano Carlos Oscar S
Published: November 2018

Motivation

Cryo electron microscopy (EM) is currently one of the main tools to reveal the structural information of biological macromolecules. The re-construction of three-dimensional (3D) maps is typically carried out following an iterative process that requires an initial estimation of the 3D map to be refined in subsequent steps. Therefore, its determination is key in the quality of the final results, and there are cases in which it is still an open issue in single particle analysis (SPA). Small angle X-ray scattering (SAXS) is a well-known technique applied to structural biology. It is useful from small nanostructures up to macromolecular ensembles for its ability to obtain low resolution information of the biological sample measuring its X-ray scattering curve. These curves, together with further analysis, are able to yield information on the sizes, shapes and structures of the analyzed particles.

Results

In this paper, we show how the low resolution structural information revealed by SAXS is very useful for the validation of EM initial 3D models in SPA, helping the following refinement process to obtain more accurate 3D structures. For this purpose, we approximate the initial map by pseudo-atoms and predict the SAXS curve expected for this pseudo-atomic structure. The match between the predicted and experimental SAXS curves is considered as a good sign of the correctness of the EM initial map.

Availability and implementation

The algorithm is freely available as part of the Scipion 1.2 software at http://scipion.i2pc.es/.
PPaxe: easy extraction of protein occurrence and interactions from the scientific literature
Authors: Castillo-Lara S , Abril J F
Published: November 2018

Motivation

Protein–protein interactions (PPIs) are very important to build models for understanding many biological processes. Although several databases hold many of these interactions, exploring them, selecting those relevant for a given subject and contextualizing them can be a difficult task for researchers. Extracting PPIs directly from the scientific literature can be very helpful for providing such context, as the sentences describing these interactions may give insights to researchers in helpful ways.

Results

We have developed PPaxe, a python module and a web application that allows users to extract PPIs and protein occurrence from a given set of PubMed and PubMedCentral articles. It presents the results of the analysis in different ways to help researchers export, filter and analyze the results easily.

Availability and implementation

PPaxe web demo is freely available at https://compgen.bio.ub.edu/PPaxe. All the software can be downloaded from https://compgen.bio.ub.edu/PPaxe/download, including a command-line version and docker containers for an easy installation.

Supplementary information

Supplementary data are available at Bioinformatics online.
Performance of Stool-testing Recommendations for Acute Gastroenteritis When Used to Identify Children With 9 Potential Bacterial Enteropathogens
Authors: Tarr Gillian A M , Chui Linda , Lee Bonita E , Pang Xiao-Li , Ali Samina , Nettel-Aguirre Alberto , Vanderkooi Otto G , Berenger Byron M , Dickinson James , Tarr Phillip I , Drews Steven , MacDonald Judy , Kim Kelly , Freedman Stephen B
Published: November 2018

Background

The ability to identify bacterial pathogens that necessitate specific clinical management or public health action in children with acute gastroenteritis is crucial to patient care and public health. However, existing stool-testing guidelines offer inconsistent recommendations, and their performance characteristics are unknown. We evaluated 6 leading gastroenteritis guidelines (eg, those of the Centers for Disease Control and Prevention and Infectious Disease Society of America) that recommend when to test children’s stool for bacterial enteropathogens.

Methods

Via 2 emergency departments in Alberta, Canada, we enrolled 2447 children <18 years old who presented with ≥3 episodes of diarrhea and/or vomiting in a 24-hour period. All participants were tested for 9 bacterial enteropathogens: Aeromonas, Campylobacter, Escherichia coli O157, other Shiga toxin–producing E. coli, enterotoxigenic E. coli, Salmonella, Shigella, Vibrio, and Yersinia. Patient data gathered at the index visit were used to determine whether guidelines would recommend testing. Sensitivity and specificity to recommend testing for children with bacterial enteropathogens were calculated for each guideline.

Results

Outcome data were available for 2391 (97.7%) participants, and 6% (144/2391) of participants tested positive for a bacterial enteropathogen. Guideline sensitivity ranged from 25.8% (95% confidence interval [CI] 18.7–33.0%) to 66.9% (95% CI 59.3–74.6%), and varied for individual pathogens. Guideline specificity for all bacterial enteropathogens ranged from 63.6% (95% CI 61.6–65.6%) to 96.5% (95% CI 95.7–97.2%).

Conclusions

No guideline provided optimally balanced performance. The most sensitive guidelines missed one-third of cases and would drastically increase testing volumes. The most specific guidelines missed almost 75% of cases.
TUBA1A mutations identified in lissencephaly patients dominantly disrupt neuronal migration and impair dynein activity
Authors: Aiken Jayne , Moore Jeffrey K , Bates Emily A
Published: November 2018

The microtubule cytoskeleton supports diverse cellular morphogenesis and migration processes during brain development. Mutations in tubulin genes are associated with severe human brain malformations known as ‘tubulinopathies’; however, it is not understood how molecular-level changes in microtubule subunits lead to brain malformations. In this study, we demonstrate that missense mutations affecting arginine at position 402 (R402) of TUBA1A α-tubulin selectively impair dynein motor activity and severely and dominantly disrupt cortical neuronal migration. TUBA1A is the most commonly affected tubulin gene in tubulinopathy patients, and mutations altering R402 account for 30% of all reported TUBA1A mutations. We show for the first time that ectopic expression of TUBA1A-R402C and TUBA1A-R402H patient alleles is sufficient to dominantly disrupt cortical neuronal migration in the developing mouse brain, strongly supporting a causal role in the pathology of brain malformation. To isolate the precise molecular impact of R402 mutations, we generated analogous R402C and R402H mutations in budding yeast α-tubulin, which exhibit a simplified microtubule cytoskeleton. We find that R402 mutant tubulins assemble into microtubules that support normal kinesin motor activity but fail to support the activity of dynein motors. Importantly, the level of dynein impairment scales with the expression level of the mutant in the cell, suggesting a ‘poisoning’ mechanism in which R402 mutant α-tubulin acts dominantly by populating microtubules with defective binding sites for dynein. Based on our results, we propose a new model for the molecular pathology of tubulinopathies that may also extend to other tubulin-related neuropathies.
Welfare regimes modify the association of disadvantaged adult-life socioeconomic circumstances with self-rated health in old age
Authors: Sieber Stefan , Cheval Boris , Orsholits Dan , Van der Linden Bernadette W , Guessous Idris , Gabriel Rainer , Kliegel Matthias , Aartsen Marja J , Boisgontier Matthieu P , Courvoisier Delphine , Burton-Jeangros Claudine , Cullati Stéphane
Published: November 2018

Background

Welfare regimes in Europe modify individuals’ socioeconomic trajectories over their life-course, and, ultimately, the link between socioeconomic circumstances (SECs) and health. This paper aimed to assess whether the associations between life-course SECs (early-life, young adult-life, middle-age and old-age) and risk of poor self-rated health (SRH) trajectories in old age are modified by welfare regimes (Scandinavian [SC], Bismarckian [BM], Southern European [SE], Eastern European [EE]).

Methods

We used data from the longitudinal SHARE survey. Early-life SECs consisted of four indicators of living conditions at age 10. Young adult-life, middle-age, and old-age SECs indicators were education, main occupation and satisfaction with household income, respectively. The association of life-course SECs with poor SRH trajectories was analysed by confounder-adjusted multilevel logistic regression models stratified by welfare regime. We included 24 011 participants (3626 in SC, 10 256 in BM, 6891 in SE, 3238 in EE) aged 50 to 96 years from 13 European countries.

Results

The risk of poor SRH increased gradually with early-life SECs from most advantaged to most disadvantaged. The addition of adult-life SECs differentially attenuated the association of early-life SECs and SRH at older age across regimes: education attenuated the association only in SC and SE regimes and occupation only in SC and BM regimes; satisfaction with household income attenuated the association across regimes.

Conclusions

Early-life SECs have a long-lasting effect on SRH in all welfare regimes. Adult-life SECs attenuated this influence differently across welfare regimes.
A systematic review of the effects of implementing clinical pathways supported by health information technologies
Authors: Neame Matthew T , Chacko Jerry , Surace Anna E , Sinha Ian P , Hawcutt Daniel B
Published: November 2018

Objective

Health information technology (HIT) interventions include electronic patient records, prescribing, and ordering systems. Clinical pathways are multidisciplinary plans of care that enable the delivery of evidence-based healthcare. Our objective was to systematically review the effects of implementing HIT-supported clinical pathways.

Materials and Methods

A systematic review protocol was developed including Medline, Embase, and CENTRAL database searches. We recorded data relating to study design, participants, intervention, and outcome characteristics and formally assessed risk of bias.

Results

Forty-four studies involving more than 270 000 patients were included. Investigation methodologies included before-after (n = 16, 36.4%), noncomparative (n = 14, 31.8%), interrupted time series (n = 5, 11.4%), retrospective cohort (n = 4, 9.1%), cluster randomized (n = 2, 4.5%), controlled before-after (n = 1, 2.3%), prospective case-control (n = 1, 2.3%), and prospective cohort (n = 1, 2.3%) study designs. Clinical decision support (n = 25, 56.8%), modified electronic documentation (n = 23, 52.3%), and computerized provider order entry (n = 23, 52.3%) were the most frequently utilized HIT interventions. The majority of studies (n = 38, 86.4%) reported benefits associated with HIT-supported pathways. These included reported improvements in objectively measured patient outcomes (n = 15, 34.1%), quality of care (n = 29, 65.9%), and healthcare resource utilization (n = 10, n = 22.7%).

Discussion

Although most studies reported improvements in outcomes, the strength of evidence was limited by the study designs that were utilized.

Conclusions

Ongoing evaluations of HIT-supported clinical pathways are justified but would benefit from study designs that report key outcomes (including adverse events) and minimize the risk of bias.
Identifying translational science through embeddings of controlled vocabularies
Authors: Ke Qing
Published: November 2018

Objective

Translational science aims at “translating” basic scientific discoveries into clinical applications. The identification of translational science has practicality such as evaluating the effectiveness of investments made into large programs like the Clinical and Translational Science Awards. Despite several proposed methods that group publications—the primary unit of research output—into some categories, we still lack a quantitative way to place articles onto the full, continuous spectrum from basic research to clinical medicine.

Materials and Methods

I learn vector representations of controlled vocabularies assigned to Medline articles to obtain a translational axis that points from basic science to clinical medicine. The projected position of a term on the translational axis, expressed by a continuous quantity, indicates the term’s “appliedness.” The position of an article, determined by the average location over its terms, quantifies the degree of its appliedness, which I term the level score.

Results

I validate the present method by comparing with previous techniques, showing excellent agreement yet uncovering significant variations of scores of articles in previously defined categories. The measure allows us to characterize the standing of journals, disciplines, and the entire biomedical literature along the basic-applied spectrum. Analysis on large-scale citation network reveals 2 main findings. First, direct citations mainly occurred between articles with similar scores. Second, shortest paths are more likely ended up with an article closer to the basic end of the spectrum, regardless of where the starting article is on the spectrum.

Conclusions

The proposed method provides a quantitative way to identify translational science.
The Genomic Landscape of Mucinous Breast Cancer
Authors: Pareja Fresia , Lee Ju Youn , Brown David N , Piscuoglio Salvatore , Gularte-Mérida Rodrigo , Selenica Pier , Da Cruz Paula Arnaud , Arunachalam Sasi , Kumar Rahul , Geyer Felipe C , Silveira Catarina , da Silva Edaise M , Li Anqi , Marchiò Caterina , Ng Charlotte K Y , Mariani Odette , Fuhrmann Laetitia , Wen Hannah Y , Norton Larry , Vincent-Salomon Anne , Brogi Edi , Reis-Filho Jorge S , Weigelt Britta
Published: November 2018

Mucinous carcinoma of the breast (MCB) is a rare histologic form of estrogen receptor (ER)-positive/HER2-negative breast cancer (BC) characterized by tumor cells floating in lakes of mucin. We assessed the genomic landscape of 32 MCBs by whole-exome sequencing and/or RNA-sequencing. GATA3 (23.8%), KMT2C (19.0%), and MAP3K1 (14.3%) were the most frequently mutated genes in pure MCBs. In addition, two recurrent but not pathognomonic fusion genes, OAZ1-CSNK1G2 and RFC4-LPP, were detected in 3/31 (9.7%) and 2/31 (6.5%) samples, respectively. Compared with ER-positive/HER2-negative common forms of BC, MCBs displayed lower PIK3CA and TP53 mutation rates and fewer concurrent 1q gains and 16q losses. Clonal decomposition analysis of the mucinous and ductal components independently microdissected from five mixed MCBs revealed that they are clonally related and evolve following clonal selection or parallel evolution. Our findings indicate that MCB represents a genetically distinct ER-positive/HER2-negative form of BC.
A Machine-Learning Approach to Predicting Smoking Cessation Treatment Outcomes
Authors: Coughlin Lara N , Tegge Allison N , Sheffer Christine E , Bickel Warren K
Published: November 2018

Aims

Most cigarette smokers want to quit smoking and more than half make an attempt every year, but less than 10% remain abstinent for at least 6 months. Evidence-based tobacco use treatment improves the likelihood of quitting, but more than two-thirds of individuals relapse when provided even the most robust treatments. Identifying for whom treatment is effective will improve the success of our treatments and perhaps identify strategies for improving current approaches.

Methods

Two cohorts (training: N = 90, validation: N = 71) of cigarette smokers enrolled in group cognitive-behavioral therapy (CBT). Generalized estimating equations were used to identify baseline predictors of outcome, as defined by breath carbon monoxide and urine cotinine. Significant measures were entered as candidate variables to predict quit status. The resulting decision trees were used to predict cessation outcomes in a validation cohort.

Results

In the training cohort, the decision trees significantly improved on chance classification of smoking status following treatment and at 6-month follow-up. The first split of all decision trees, which was delay discounting, significantly improved on chance classification rates in both the training and validation cohort. Delay discounting emerged as the single best predictor of group CBT treatment response with an average baseline discount rate of ln(k) = −7.1, correctly predicting smoking status of 80% of participants at posttreatment and 81% of participants at follow-up.

Conclusions

This study provides a first step toward personalized care for smoking cessation though future work is needed to identify individuals that are likely to be successful in treatments beyond group CBT.

Implications

This study provides a first step toward personalized care for smoking cessation. Using a novel machine-learning approach, baseline measures of clinical and executive functioning are used to predict smoking cessation outcomes following group CBT. A decision point is recommended for the single best predictor of treatment outcomes, delay discounting, to inform future research or clinical practice in an effort to better allocate patients to treatments that are likely to work.
Responsiveness of clinical and ultrasound outcome measures in musculoskeletal systemic lupus erythematosus
Authors: Mahmoud Khaled , Zayat Ahmed S , Yusof Yuzaiful , Hensor Elizabeth , Conaghan Philip G , Emery Paul , Vital Edward M
Published: November 2018

Objective

To assess the responsiveness of clinical outcome measures in musculoskeletal SLE compared with US.

Methods

A prospective pilot study was conducted in consecutive SLE patients with inflammatory musculoskeletal symptoms. Clinical assessments including SLEDAI, BILAG, 28 tender and swollen joint counts, physician and patient visual analogue scales (VAS), and US were performed at 0, 2 and 4 weeks following 120 mg i.m. methylprednisolone acetate. Responsiveness was analysed using changes and effect sizes using Cohen’s criteria.

Results

Twenty patients were recruited. Fifteen out of 20 had clinical swelling at baseline. All clinical and US parameters were significantly improved at week 4 (all P ⩽ 0.01). Musculoskeletal-BILAG score improved in 16/20. Musculoskeletal-SLEDAI improved in 7/20. SLE responder index 4 criteria were assessed in 19 patients with SLEDAI ⩾4 at baseline and were met in 9/19 at 4 weeks. Effect sizes at 4 weeks were large (>0.5) for US, physician VAS and BILAG, and medium (>0.3) for joint counts and SLEDAI. Large effect sizes for improvement in US grey-scale and power Doppler were observed in both SLE responder index 4 responders (r = −0.51 and −0.56, respectively) and non-responders (r = −0.62 and −0.59, respectively) at 4 weeks.

Conclusion

This is the first study to measure the responsiveness of clinical outcome measures in musculoskeletal SLE against an objective inflammation measure. BILAG and physician VAS were the most responsive clinical instruments. US was highly responsive in musculoskeletal SLE, while SLEDAI and joint counts appeared suboptimal for detection of improvement. These results suggest that clinical trials based on the SLEDAI and SLE responder index 4 may underestimate the efficacy of therapy in SLE.
Combined Expression of Genetic Adjuvants Via mRNA Electroporation Exerts Multiple Immunostimulatory Effects on Antitumor T Cells
Authors: Weinstein-Marom Hadas , Levin Noam , Pato Aviad , Shmuel Nofar , Sharabi-Nov Adi , Peretz Tamar , Eisenberg Galit , Lotem Michal , Itzhaki Orit , Besser Michal J. , Gross Gideon
Published: November 2018

Adoptive transfer of tumor-infiltrating lymphocytes (TILs) or gene-modified T cells expressing antitumor TCRs or chimeric antigen receptors often yields a high rate of clinical response in several types of cancer. New approaches for enhancing the functional properties of antitumor T cells could improve the clinical outcome of these treatments. To this end, we created 3 classes of genes, each designed to operate autonomously upon expression in T cells. We recently reported on the enhancing effects of constitutively active toll-like receptor 4 (caTLR4), membrane (mem) interleukin-2, memIL-12, and memIL-15, and self-oligomerizing, constitutively active CD40 (caCD40). Here, we evaluated their combined effects on peripheral blood CD8 T cells and different antimelanoma TIL cultures following mRNA electroporation. Expression in CD8 T cells induced transient production of interferon-γ and prolonged and robust upregulation of CD25, CD69, 4-1BB, and OX40. The adjuvants enhanced cytolytic activity of TILs and production of interferon-γ and TNF-α in the presence of autologous, but not mismatched, melanoma for at least 3 days after electroporation. Expression of the 3 adjuvants in young TILs from different patients markedly increased the expression of CD25, OX40, 4-1BB, CD127, and CD28 and exhibited cooperative and, at times, synergistic effects. Furthermore, predefined mixtures of mRNA encoding these adjuvants markedly enhanced the specific antitumor response of selected TILs and killing of autologous melanoma cells by young TILs. Our findings suggest that combinations of these new genetic adjuvants can substantially improve the functional properties of antitumor T cells, offering a new tool of unique versatility in adoptive cell therapy.
Overall Survival of Men and Women With Breast Cancer According to Tumor Subtype
Authors: Leone Julieta , Zwenger Ariel O. , Leone Bernardo A. , Vallejo Carlos T. , Leone José P.
Published: November 2018

Objectives:

To analyze differences in overall survival (OS) between male breast cancer (MBC) and female breast cancer (FBC) according to tumor subtype compared with other factors.

Materials and Methods:

We evaluated men and women with breast cancer between 2010 and 2013 with known hormone receptor (HR) status and human epidermal growth factor receptor 2 (HER2) status reported to the National Cancer Institute’s Surveillance, Epidemiology, and End Results program. Patient characteristics were compared between groups. Univariate and multivariate analyses were performed to determine the effect of each variable on OS. Breast cancer–specific survival was a secondary endpoint.

Results:

We included 1187 MBC and 166,054 FBC. Median follow-up was 21 months (range, 1 to 48) for both groups. OS at 3 years for MBC and FBC was 85.6% and 90.4%, respectively (P=0.0002). MBC were more ductal, had higher grade, presented with more advanced stage and were often HR+/HER2− (each P<0.0001). MBC had worse OS than FBC in HR+/HER2− (Hazard ratio [HaR], 1.5; P=0.0005), HR+/HER2+ (HaR, 2.8; P<0.0001) and triple negative (HaR, 4.3; P<0.0001) (P
interaction<0.02). MBC had significantly worse OS than FBC in stages I and II, but similar OS in stages III and IV (P
interaction<0.01). In multivariate analysis, HR+/HER2+ was the only subtype with significant differences in OS between MBC and FBC (HaR, 2.0; P=0.002).

Conclusions:

OS was significantly different in both groups. Men had worse OS in early stages while similar OS in stages III and IV. There were significant differences in OS according to tumor subtype; compared with women, men with HR+/HER2+ tumors had twice the risk of death.
Management of Unresectable T4b Esophageal Cancer
Authors: Cushman Taylor R. , Shaaban Sherif G. , Moreno Amy C. , Lin Chi , Verma Vivek
Published: November 2018

Purpose:

Patients with unresectable cT4b esophageal cancer (EC) are rare and largely excluded from prospective trials. As a result, current treatment recommendations are based on limited evidence. This study sought to evaluate national practice patterns and outcomes for this population and evaluated 3 primary cohorts: patients receiving chemotherapy (CT) with or without subtherapeutic radiotherapy (RT), definitive chemoradiotherapy (CRT), or CT with or without RT followed by definitive surgery.

Materials and Methods:

The National Cancer Data Base was queried for cT4b Nany M0 EC. Exclusion criteria were patients with unspecified staging, palliative treatment, improper, or no histologic confirmation, or lack of CT. Multivariable logistic regression determined factors predictive of receiving surgical therapy. Kaplan-Meier analysis evaluated overall survival (OS), and Cox proportional hazards modeling determined variables associated with OS.

Results:

Altogether, 519 patients met inclusion criteria; 195 (38%) underwent CT, 291 (56%) underwent definitive CRT, and 33 (6%) underwent surgical-based therapy. Surgery was more likely performed in patients residing in rural areas, living farther from the treating facility, and N1 status (P<0.05 for all). Median OS in the respective cohorts were 6.0, 12.7, and 43.9 months (P<0.001). On multivariate Cox proportional hazards modeling, among others, nonsurgical treatment was associated with poorer OS (P<0.05 for both).

Conclusions:

In the largest study to date evaluating patterns of care for cT4b EC, as compared with CT alone, addition of definitive RT was associated with higher OS. Although causation is clearly not implied, well-selected responders to CT and/or RT may be able to undergo resection and numerically prolonged survival, but patient selection remains paramount.
Nurses' Competence Caring for Hospitalized Patients With Ventricular Assist Devices
Authors: Casida Jesus M. , Abshire Martha , Widmar Brian , Combs Pamela , Freeman Regi , Baas Linda
Published: November 2018

Background

Nursing care is an essential component of the delivery of high-quality patient care for advanced heart failure patients with ventricular assist devices (VADs). However, there is little information about how VAD patient care competence is formed, and there are no empirical data regarding the bed nurses' competence.

Objectives

The aim of this study was to explain how nurses perceived their competence related to VAD technology and how they utilized resources to equip themselves for the management of patients with implantable VADs.

Methods

An exploratory correlational research design was used in this study. Online surveys including demographic and work characteristics questionnaires as well as VAD Innovation in Nursing Appraisal Scale (knowledge, adoption, and communication) were completed by 237 critical-care unit and progressive care unit (PCU) nurses.

Results

Ventricular assist device knowledge, adoption, and communication of innovation mean scores were 3.9 ± 0.6, 3.9 ± 0.8, and 3.7 ± 0.9, respectively, indicating moderate/high levels. Critical-care unit nurses reported higher levels of knowledge (3.7 vs 3.6) and adoption (4.0 vs 3.8; P < .05) of innovation than did the PCU nurses, with no differences in communication. Compared with PCU nurses, critical-care unit nurses were more likely to seek VAD competence-related information using mass media. Innovation and adoption were associated with years of nursing experience and some hospital characteristics.

Conclusion

Critical-care unit nurses have higher self-reported VAD care competence than PCU nurses. Further research is needed to confirm the findings and link nurse competence with VAD patient outcomes.
Partial Stapled Hemorrhoidopexy Versus Circumferential Stapled Hemorrhoidopexy for Grade III to IV Prolapsing Hemorrhoids: A Randomized, Noninferiority Trial
Authors: Lin Hong-Cheng , He Qiu-Lan , Shao Wan-Jin , Chen Xin-Lin , Peng Hui , Xie Shang-Kui , Wang Xiao-Xue , Ren Dong-Lin
Published: November 2018

BACKGROUND:

Long-term outcomes and efficacy of partial stapled hemorrhoidopexy are not known.

OBJECTIVE:

The purpose of this study was to compare the long-term clinical efficacy and safety of partial stapled hemorrhoidopexy with circumferential stapled hemorrhoidopexy.

DESIGN:

This was a parallel group, randomized, noninferiority clinical trial.

SETTINGS:

The study was conducted at a single academic center.

PATIENTS:

Patients with grade III/IV hemorrhoids between August 2011 and November 2013 were included.

INTERVENTIONS:

Three hundred patients were randomly assigned to undergo either partial stapled hemorrhoidopexy (group 1, n = 150) or circumferential stapled hemorrhoidopexy (group 2, n = 150).

MAIN OUTCOME MEASURES:

The primary outcome was the rate of recurrent prolapse at a median follow-up period of 5 years with a predefined noninferiority margin of 3.75%. Secondary outcomes included incidence and severity of postoperative pain, fecal urgency, anal continence, and the frequency of specific complications, including anorectal stenosis and rectovaginal fistula.

RESULTS:

The visual analog scores in group 1 were less than those in group 2 (p < 0.001). Fewer patients in group 1 experienced postoperative urgency compared with those in group 2 (p = 0.001). Anal continence significantly worsened after both procedures, but the difference between preoperative and postoperative continence scores was higher for group 2 than for group 1. Postoperative rectal stenosis did not develop in patients in group 1, although it occurred in 8 patients (5%) in group 2 (p = 0.004). The 5-year cumulative recurrence rate between group 1 (9% (95% CI, 4%–13%)) and group 2 (12% (95% CI, 7%–17%)) did not differ significantly (p = 0.137), and the difference was within the noninferiority margin (absolute difference, –3.33% (95% CI, –10.00% to 3.55%)).

LIMITATIONS:

The study was limited because it was a single-center trial.

CONCLUSIONS:

Partial stapled hemorrhoidopexy is noninferior to circumferential stapled hemorrhoidopexy for patients with grade III to IV hemorrhoids at a median follow-up period of 5 years. However, partial stapled hemorrhoidopexy was associated with reduced postoperative pain and urgency, better postoperative anal continence, and minimal risk of rectal stenosis. See Video Abstract at http://links.lww.com/DCR/A790.

Trial registration (chictr.org) identifier is chiCTR-trc-11001506.
1-Minute Sit-to-Stand Test
Authors: Bohannon Richard W. , Crouch Rebecca
Published: November 2018

Purpose:

Tests for quantifying exercise capacity that are applicable in diverse settings are needed. The 1-min sit-to-stand test (1-MSTST) is such a test. This systematic review summarizes the literature addressing 1-MSTST procedures, performance, and clinimetric properties.

Methods:

Three online databases, hand searches, and an expert consultant were used to identify literature relevant to the aims of this review. Inclusion required that studies addressed the 1-MSTST, focused on adults, and were written in English.

Results:

Seventeen articles were identified that met the inclusion criteria. The populations assessed included adults without identified pathologies and adults with lung disease, renal disease, stroke, osteoporosis, or receiving palliative care. The 1-MSTST typically involves an armless chair and the performance of as many sit-to-stand actions as possible in 1 min without using the upper limbs. The mean number of 1-MSTST repetitions reported in the literature achieved ranged from 8.1 (patients with stroke) to 50.0 (young men). Numerous studies supported the convergent and known-groups validity and the test-retest reliability of the test. The test has been shown to be responsive. Normative reference values are available.

Conclusions:

The literature provides considerable support for using the 1-MSTST to quantify exercise capacity. Broader use of this test may be indicated, particularly where space and time are limited.
Organizational facilitators and barriers to optimal APRN practice: An integrative review
Authors: Schirle Lori , Norful Allison A. , Rudner Nancy , Poghosyan Lusine
Published: November 2018

Background:

The organizational environment can foster or impede full deployment of advance practice registered nurses (APRNs), affecting the quality of care and patient outcomes. Given the critical role APRNs play in health care, it is important to understand organizational factors that promote or hinder APRN practice to maximize the potential of this workforce in health care systems.

Purpose:

The aim of this study was to synthesize evidence about APRN practice environments, identify organizational facilitators and barriers, and make recommendations for better APRN utilization.

Methods:

A literature search was conducted in CINAHL, PubMed, and PsychInfo, yielding 366 studies. No time or geographic limitations were applied. Study quality was appraised using the National Institutes of Health National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies and The Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Studies.

Results:

Thirty studies conducted in the United States, Canada, and the Netherlands met inclusion criteria. The majority of the studies involved nurse practitioners. Facilitators to optimal practice environment were autonomy/independent practice and positive physician/APRN relations. Barriers included policy restrictions on practice, poor physician relations, poor administrator relations, and others’ lack of understanding of the APRN role. Barriers correlate with job dissatisfaction and increased intent to leave job.

Practice Implications:

The review highlights the importance of physician and administration relations, organizational-level policies, and colleagues’ understanding of the APRN role in promoting effective practice environments. Organizations should align policy reform efforts with factors that foster positive APRN practice environments to efficiently and effectively utilize this increasingly vital workforce. Future research is warranted.
Variation of hospital-based adoption of care coordination services by community-level social determinants of health
Authors: Chen Jie , DuGoff Eva Hisako , Novak Priscilla , Wang Min Qi
Published: November 2018

Background

Hospital investments in care coordination services and innovative delivery models represent an important source for improving care efficiency and population health.

Objective

The aim of this study was to explore variation of hospital-initiated care coordination services and participation in Accountable Care Organizations (ACOs) by community characteristics within an organizational theory framework.

Methods

Our main data sets included the 2015 American Hospital Association Annual Survey, Survey of Care Systems and Payment, American Community Survey, and Area Health Resource File. Two main outcomes were (a) hospital-reported initiation of care coordination practices (such as chronic disease management, post-hospital discharge continuity of care, and predictive analytics) and (b) participation in ACO models. State fixed-effects models were used to test the association between the adoption of care coordination practices and hospital characteristics, community-level sociodemographic characteristics, and health policies.

Results

Hospitals with large bed size, located in urban areas, and/or with high volume of operations were more likely to adopt care coordination practices and participate in the ACO models. Hospitals serving communities with high uninsurance rates and/or poverty rates were significantly less likely to provide care coordination practices. More stringent Community Benefit Laws (CBLs) were positively associated with the implementation of care coordination practices suggesting strong normative impacts of CBLs.

Conclusion

Greater hospital-initiated care coordination practices and innovative ACO models were available in well-resourced areas. Policymakers may consider increasing resources for care coordination practices in rural, underserved, and high-poverty–high-uninsured areas to ensure that vulnerable populations can benefit from these services.