bluuebunny/crossref_metadata_2025 huggingface dataset:
Chimeric antigen receptor preparation from hybridoma to T-cell expression
Authors: Köksal Hakan , Baken Elizabeth , Warren David John , Løset Geir Åge , Inderberg Else Marit , Wälchli Sébastien
Published: May 2019

The successful use of chimeric antigen receptor (CAR) for hematological cancer treatment has influenced the direction taken in translational research toward an increasing focus on personalized targeted immunotherapy. Thus, a growing number of labs worldwide are now interested in testing their old antibody collections in this format to broaden the spectrum of utility and improve safety and efficacy. We herein present a straightforward protocol for the identification of an antibody from a hybridoma and the design of the single chain fragment that will be placed on the extracellular part of the CAR construct. We further show how to test the expression and the activity of the construct in primary T cells. We illustrate our demonstration with two new CARs targeted against the B cell receptor, more precisely the light chains κ and λ, that represent potential alternatives to the CD19 CAR used in the treatment of B-cell malignancies.
Metastatic Basal Cell Carcinoma
Authors: Laga Alvaro C , Schaefer Inga Marie , Sholl Lynette M , French Christopher A , Hanna John
Published: May 2019

Objectives

Diagnosis of metastatic basal cell carcinoma (BCC) remains challenging, in part due to its rarity. With the advent of molecularly targeted therapies, recognition of this entity is more important than ever.

Methods

We identified 11 cases of metastatic BCC over a 13-year period. We analyzed these tumors in conjunction with their respective primary tumors by histomorphologic, immunohistochemical, and molecular genetic analyses.

Results

We identified three morphologic patterns of metastasis in BCC. The most common (seven cases) was characterized by completely typical features of BCC. Two cases showed marked squamous differentiation within BCC. The final two cases showed exclusively features of a poorly differentiated carcinoma. One of these was definitively classified by molecular analysis, as both the primary and metastatic tumors harbored the same inactivating PTCH1 mutation.

Conclusions

This study illustrates multiple distinct morphologic patterns in metastatic BCC and highlights the utility of ancillary molecular testing for accurate diagnosis.
Resolution of HCV-Autoimmune Hepatitis Overlap Syndrome With Antiviral Treatment
Authors: Putra Juan , Schiano Thomas D , Fiel M Isabel
Published: May 2019

Objectives

To evaluate histologic changes occurring in patients having chronic hepatitis C and autoimmune hepatitis overlap (HCV-AIH), and who achieved virologic cure using direct-acting antiviral agents (DAA).

Methods

Characteristics of HCV-AIH patients who underwent paired liver biopsies before and after receiving DAA treatment from 2011 to 2018 were evaluated.

Results

Five HCV-AIH patients (three male; mean age, 60.4 years) underwent paired liver biopsies (average interval, 2.3 years) before and after achieving cure with DAA treatment. All patients showed virologic response, while four showed decreased inflammation, and three cases showed features of fibrosis regression. Immunohistochemical staining demonstrated significant decrease in plasma cell count in three patients (20.6 vs 11.9 plasma cells/high power field; P = .02, t test).

Conclusions

Histologic improvements in inflammation and fibrosis are noted in most HCV-AIH patients after DAA treatment, suggesting that the autoimmune component of the HCV-AIH overlap syndrome is merely a secondary phenomenon of viral infection.
Patient-reported depression treatment and future treatment preferences: an observational study in general practice
Authors: Hetlevik Øystein , Garre-Fivelsdal Gina , Bjorvatn Bjørn , Hjørleifsson Stefan , Ruths Sabine
Published: May 2019

Background

Depression is prevalent in general practice, but few studies have explored patient-reported depression care.

Aim

To investigate patient-reported treatment received for depression and future treatment preferences among adult patients visiting their GP, and to evaluate the associations with sex, age and educational level.

Design and Setting

A cross-sectional survey was conducted in general practices in Norway from 2016 to 2017.

Methods

Altogether, 2335 consecutive patients (response rate, 89.2%) in the GPs’ waiting rooms answered a questionnaire about their received depression treatment and treatment preferences in case of future depression.

Results

The study population (N = 2239) had a mean age of 48.6 ± 17.7 years (range 18–91), 60.1% were women. Of the 770 patients reporting to have received depression treatment, 39.1% were treated exclusively by their GP while 52.5% also were referred to a psychologist/psychiatrist. Older age was positively associated with medication and negatively associated with referrals to psychologist/psychiatrist. People with high education had lower odds for receiving medication (odds ratios [OR], 0.49; 95% confidence intervals [CI]: 0.30–0.80) compared to those with low education. If future depression, 81.6% of the respondents would discuss this with their GP, 60.9% would prefer talking therapy with their GP, 22.5% medication, and 52.9% referral to psychologist or psychiatrist.

Conclusion

One-third of the patients attending their GPs had consulted with them at some time concerning depression the case of future depression, most patients preferred talking therapy with the GP. This finding warrants increased research focus on the GP’s role in depression care.
Primary care providers’ responses to pregnancy intention screening challenges: community-based participatory research at an urban community health centre
Authors: Srinivasulu Silpa , Falletta Katherine A , Bermudez Dayana , Almonte Yolyn , Baum Rachel , Coriano Madeline , Grosso Ashley , Iglehart Kathryn , Mota Cathy , Rodriguez Laura , Taveras Jecenia , Tobier Natalie , Garbers Samantha V
Published: May 2019

Background

Incorporating pregnancy intention screening into primary care to address unmet preconception and contraception needs may improve delivery of family planning services. A notable research gap exists regarding providers’ experiences conducting this screening in primary care.

Objective

To explore primary care providers’ perceived challenges in conducting pregnancy intention screening with women of reproductive age and to identify strategies to discuss this in primary care settings.

Methods

This qualitative study emerged from a 2017 community-based participatory research project. We conducted semi-structured, in-depth interviews with 10 primary care providers who care for women of reproductive age at an urban federally qualified health centre. Analysis consisted of interview debriefing, transcript coding and content analysis with the Community Advisory Board.

Results

Across departments, respondents acknowledged difficulties conducting pregnancy intention screening and identified strategies for working with patients’ individual readiness to discuss pregnancy intention. Strategies included: linking patients’ health concerns with sexual and reproductive health, applying a shared decision-making model to all patient–provider interactions, practicing goal setting and motivational interviewing, fostering non-judgmental relationships and introducing pregnancy intention in one visit but following up at later times when more relevant for patients.

Conclusions

Opportunities exist for health centres to address pregnancy intention screening challenges, such as implementing routine screening and waiting room tools to foster provider and patient agency and sharing best practices with providers across departments by facilitating comprehensive training and periodic check-ins. Exploring providers’ experiences may assist health centres in improving pregnancy intention screening in the primary care setting.
Chaperonin overproduction and metabolic erosion caused by mutation accumulation in Escherichia coli
Authors: Aguilar-Rodríguez José , Fares Mario A , Wagner Andreas
Published: May 2019

Bacterial cells adapting to a constant environment tend to accumulate mutations in portions of their genome that are not maintained by selection. This process has been observed in bacteria evolving under strong genetic drift, and especially in bacterial endosymbionts of insects. Here, we study this process in hypermutable Escherichia coli populations evolved through 250 single-cell bottlenecks on solid rich medium in a mutation accumulation experiment that emulates the evolution of bacterial endosymbionts. Using phenotype microarrays monitoring metabolic activity in 95 environments distinguished by their carbon sources, we observe how mutation accumulation has decreased the ability of cells to metabolize most carbon sources. We study if the chaperonin GroEL, which is naturally overproduced in bacterial endosymbionts, can ameliorate the process of metabolic erosion, because of its known ability to buffer destabilizing mutations in metabolic enzymes. Our results indicate that GroEL can slow down the negative phenotypic consequences of genome decay in some environments.
RNA editing alterations in a multi-ethnic Alzheimer disease cohort converge on immune and endocytic molecular pathways
Authors: Gardner Olivia K , Wang Lily , Van Booven Derek , Whitehead Patrice L , Hamilton-Nelson Kara L , Adams Larry D , Starks Takiyah D , Hofmann Natalia K , Vance Jeffery M , Cuccaro Michael L , Martin Eden R , Byrd Goldie S , Haines Jonathan L , Bush William S , Beecham Gary W , Pericak-Vance Margaret A , Griswold Anthony J
Published: May 2019

Little is known about the post-transcriptional mechanisms that modulate the genetic effects in the molecular pathways underlying Alzheimer disease (AD), and even less is known about how these changes might differ across diverse populations. RNA editing, the process that alters individual bases of RNA, may contribute to AD pathogenesis due to its roles in neuronal development and immune regulation. Here, we pursued one of the first transcriptome-wide RNA editing studies in AD by examining RNA sequencing data from individuals of both African-American (AA) and non-Hispanic White (NHW) ethnicities. Whole transcriptome RNA sequencing and RNA editing analysis were performed on peripheral blood specimens from 216 AD cases (105 AA, 111 NHW) and 212 gender matched controls (105 AA, 107 NHW). 449 positions in 254 genes and 723 positions in 371 genes were differentially edited in AA and NHW, respectively. While most differentially edited sites localized to different genes in AA and NHW populations, these events converged on the same pathways across both ethnicities, especially endocytic and inflammatory response pathways. Furthermore, these differentially edited sites were preferentially predicted to disrupt miRNA binding and induce nonsynonymous coding changes in genes previously associated with AD in molecular studies, including PAFAH1B2 and HNRNPA1. These findings suggest RNA editing is an important post-transcriptional regulatory program in AD pathogenesis.
Barriers to Mental Health Care for Transgender and Gender-Nonconforming Adults: A Systematic Literature Review
Authors: Snow Annie , Cerel Julie , Loeffler Diane N , Flaherty Chris
Published: May 2019

Contemporary research suggests that transgender and gender-nonconforming (TGNC) adults encounter formidable barriers to health care, including access to quality therapeutic interventions. This systematic review is one of the first to specifically explore obstacles to TGNC mental health care. A rigorous literature review identified eight relevant studies: six qualitative designs and two quantitative designs. Thematic synthesis revealed three major barriers to care and five corresponding subthemes: (1) personal concerns, involving fear of being pathologized or stereotyped and an objection to common therapeutic practices; (2) incompetent mental health professionals, including those who are unknowledgeable, unnuanced, and unsupportive; and (3) affordability factors. Results indicate an acute need for practitioner training to ensure the psychological well-being of TGNC clients.
Pharyngeal Jaws Converge by Similar Means, Not to Similar Ends, When Minnows (Cypriniformes: Leuciscidae) Adapt to New Dietary Niches
Authors: Pos Kelsie M , Farina Stacy C , Kolmann Matthew A , Gidmark Nicholas J
Published: May 2019

Convergent evolution is at the forefront of many form-function studies. There are many examples of multiple independent lineages evolving a similar morphology in response to similar functional demands, providing a framework for testing hypotheses of form-function evolution. However, there are numerous clades with underappreciated convergence, in which there is a perceived homogeneity in morphology. In these groups, it can be difficult to investigate causal relationships of form and function (e.g., diet influencing the evolution of jaw morphology) without the ability to disentangle phylogenetic signal from convergence. Leuciscids (Cypriniformes: Leuciscidae; formerly nested within Cyprinidae) are a species-rich clade of fishes that have diversified to occupy nearly every freshwater trophic niche, yet are considered to have relatively low morphological diversity relative to other large freshwater clades. Within the North American leuciscids, many genera contain at least one herbivore, insectivore, and larvaphage. We created 3D models from micro-computed tomography scans of 165 leuciscid species to measure functionally relevant traits within the pharyngeal jaws of these fishes. Using a published phylogeny, we tested these metrics for evolutionary integration, phylogenetic signal, and correlation with diet. Measurements of the pharyngeal jaws, muscle attachment areas, and teeth showed strong positive evolutionary correlation with each other and negative evolutionary correlation with measurements of the inter-ceratobranchial ligament (ICB ligament). Using diet data from published literature, we found extensive dietary convergence within Leuciscidae. The most common transitions we found were between herbivorous and invertivorous taxa and between insectivore types (aquatic vs. terrestrial). We document a trade-off in which herbivorous leuciscids have large teeth, short ICB ligaments, and large muscle attachment areas, whereas insectivorous leuciscids showed the opposite pattern. Inverse patterns of morphological integration between the ICB ligament the rest of the pharyngeal jaw correspond this dietary trade-off, which indicates that coordinated evolution of morphological traits contributes to functional diversity in this clade. However, these patterns only emerge in the context of phylogeny, meaning that the pharyngeal jaws of North American leuciscids converge by similar means (structural changes in response to dietary demands), but not necessarily to similar ends (absolute phenotype).
The Importance of Inclusion, Diversity, and Equity to the Future of the Infectious Diseases Society of America
Authors: Powderly William G
Published: May 2019

The Infectious Diseases Society of America (IDSA) has grown and evolved considerably since its foundation in 1963 as an academic professional society. It currently has >11 000 members, both domestic and international, drawn from the breadth of infectious diseases practice, from basic research to public health. Governance of the Society has not evolved as rapidly, and, in the last few years, it was increasingly evident to many members that the IDSA leadership was less representative of the membership than it ought to be. As a result of a rigorous review of its governance structure, the Society has committed to a policy of inclusion, diversity, access, and equity. It has also reformed the methods by which future IDSA leaders are identified and given roles. These changes should increase the opportunities for all members of the Society to participate in its volunteer leadership.
Knowing More of the Iceberg: How Detecting a Greater Proportion of Carbapenem-Resistant Enterobacteriaceae Carriers Influences Transmission
Authors: Bartsch Sarah M , Wong Kim F , Stokes-Cawley Owen J , McKinnell James A , Cao Chenghua , Gussin Gabrielle M , Mueller Leslie E , Kim Diane S , Miller Loren G , Huang Susan S , Lee Bruce Y
Published: May 2019

Background

Clinical testing detects a fraction of carbapenem-resistant Enterobacteriaceae (CRE) carriers. Detecting a greater proportion could lead to increased use of infection prevention and control measures but requires resources. Therefore, it is important to understand the impact of detecting increasing proportions of CRE carriers.

Methods

We used our Regional Healthcare Ecosystem Analyst–generated agent-based model of adult inpatient healthcare facilities in Orange County, California, to explore the impact that detecting greater proportions of carriers has on the spread of CRE.

Results

Detecting and placing 1 in 9 carriers on contact precautions increased the prevalence of CRE from 0% to 8.0% countywide over 10 years. Increasing the proportion of detected carriers from 1 in 9 up to 1 in 5 yielded linear reductions in transmission; at proportions >1 in 5, reductions were greater than linear. Transmission reductions did not occur for 1, 4, or 5 years, varying by facility type. With a contact precautions effectiveness of ≤70%, the detection level yielding nonlinear reductions remained unchanged; with an effectiveness of >80%, detecting only 1 in 5 carriers garnered large reductions in the number of new CRE carriers. Trends held when CRE was already present in the region.

Conclusion

Although detection of all carriers provided the most benefits for preventing new CRE carriers, if this is not feasible, it may be worthwhile to aim for detecting >1 in 5 carriers.
Spatial Assessment of Contact Between Humans and Anopheles and Aedes Mosquitoes in a Medium-Sized African Urban Setting, Using Salivary Antibody–Based Biomarkers
Authors: Sagna André B , Kassié Daouda , Couvray Agnès , Adja Akré Maurice , Hermann Emmanuel , Riveau Gilles , Salem Gérard , Fournet Florence , Remoue Franck
Published: May 2019

Background

Anarchic and poorly controlled urbanization led to an increased risk of mosquito-borne diseases (MBD) in many African cities. Here, we evaluate the spatial heterogeneity of human exposure to malaria and arboviral disease vectors in an urban area of northern Senegal, using antibody-based biomarkers of exposure to Anopheles and Aedes mosquito bites.

Methods

A cross-sectional study was undertaken during the rainy season of 2014 in 4 neighborhoods of Saint-Louis, a city in northern Senegal. Among children aged 6–59 months in each neighborhood, the dried blood spot technique was used to evaluate immunoglobulin G (IgG) responses to both gSG6-P1 (Anopheles) and Nterm–34-kDa (Aedes) salivary peptides as validated biomarkers of respective mosquito bite exposure.

Results

IgG response levels to gSG6-P1 and Nterm–34-kDa salivary peptides varied significantly between the 4 neighborhoods (P < .0001). The level of exposure to Aedes bites also varied according to household access to sanitation services (P = .027), whereas that of exposure to Anopheles bites varied according to insecticide-treated bed net use (P = .006). In addition, spatial clusters of high contact between humans and mosquitoes were identified inside 3 neighborhoods.

Conclusions

Antibody-based biomarkers of exposure to Anopheles and Aedes mosquito bites could be helpful tools for evaluating the heterogeneity of exposure to malaria and arboviral disease vectors by national control programs.
UK phenomics platform for developing and validating electronic health record phenotypes: CALIBER
Authors: Denaxas Spiros , Gonzalez-Izquierdo Arturo , Direk Kenan , Fitzpatrick Natalie K , Fatemifar Ghazaleh , Banerjee Amitava , Dobson Richard J B , Howe Laurence J , Kuan Valerie , Lumbers R Tom , Pasea Laura , Patel Riyaz S , Shah Anoop D , Hingorani Aroon D , Sudlow Cathie , Hemingway Harry
Published: May 2019

Objective

Electronic health records (EHRs) are a rich source of information on human diseases, but the information is variably structured, fragmented, curated using different coding systems, and collected for purposes other than medical research. We describe an approach for developing, validating, and sharing reproducible phenotypes from national structured EHR in the United Kingdom with applications for translational research.

Materials and Methods

We implemented a rule-based phenotyping framework, with up to 6 approaches of validation. We applied our framework to a sample of 15 million individuals in a national EHR data source (population-based primary care, all ages) linked to hospitalization and death records in England. Data comprised continuous measurements (for example, blood pressure; medication information; coded diagnoses, symptoms, procedures, and referrals), recorded using 5 controlled clinical terminologies: (1) read (primary care, subset of SNOMED-CT [Systematized Nomenclature of Medicine Clinical Terms]), (2) International Classification of Diseases–Ninth Revision and Tenth Revision (secondary care diagnoses and cause of mortality), (3) Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures, Fourth Revision (hospital surgical procedures), and (4) DM+D prescription codes.

Results

Using the CALIBER phenotyping framework, we created algorithms for 51 diseases, syndromes, biomarkers, and lifestyle risk factors and provide up to 6 validation approaches. The EHR phenotypes are curated in the open-access CALIBER Portal (https://www.caliberresearch.org/portal) and have been used by 40 national and international research groups in 60 peer-reviewed publications.

Conclusions

We describe a UK EHR phenomics approach within the CALIBER EHR data platform with initial evidence of validity and use, as an important step toward international use of UK EHR data for health research.
Smiling Signals Intrinsic Motivation
Authors: Cheng Yimin , Mukhopadhyay Anirban , Williams Patti
Published: May 2019

The nature of a person’s motivation (whether it is intrinsic or extrinsic) is a key predictor of how committed they are to a task, and hence how well they are likely to perform at it. However, it is difficult to reliably communicate and make inferences about such fine nuances regarding another person’s motivation. Building on the social functional view of emotion and the evolutionary and psychophysical characteristics of facial expression of emotions, this research suggests that displayed enjoyment, as evidenced by the size and type of someone’s smile, can serve as a strong nonverbal signal of intrinsic motivation. Taking the perspective of both actors and observers, five studies show that people infer greater intrinsic motivation when they see others display large Duchenne (vs. small) smiles, and that actors intuit this relationship, strategically displaying larger and more Duchenne-like smiles if they have an accessible goal to signal intrinsic (vs. extrinsic or no specific) motivation.
Lutzia (Metalutzia) chiangmaiensis n. sp. (Diptera: Culicidae), Formal Name for the Chiang Mai (CM) Form of the Genus Lutzia in Thailand
Authors: Somboon Pradya , Harbach Ralph E
Published: May 2019

The Chiang Mai (CM) form of the genus Lutzia, subgenus Metalutzia, in Thailand is diagnosed and formally named Lt. chiangmaiensis Somboon & Harbach, n. sp. The species is contrasted with related species, and information is provided on its bionomics and distribution.
Lemongrass and Cinnamon Bark: Plant Essential Oil Blend as a Spatial Repellent for Mosquitoes in a Field Setting
Authors: Peach Daniel A H , Almond Max , Gries Regine , Gries Gerhard
Published: May 2019

Plant essential oils (EOs) have been considered as spatial repellents to help disrupt the pathogen transmission cycle of mosquitoes. Our objective was to assess spatial repellency effects of EOs on the tropical yellow fever mosquito, Aedes aegypti (L.) (Diptera: Culicidae) and on local mosquito populations in coastal British Columbia (Canada). In laboratory experiments using protocols of the World Health Organization, three of the solitary EOs tested proved repellent to Ae. aegypti: cinnamon bark, lemongrass, and rosemary. Binary combinations of select EOs enhanced the repellent effect of single EOs through synergistic interactions. The EO blend of geranium and peppermint lowered the RD50 (the dose required to obtain 50% repellency) of each solitary EO by >1,000-fold. Compared with binary EO blends, ternary EO blends were typically less repellent to mosquitoes, possibly due to a dilution effect of the most effective EO constituent(s) in the blend. In field experiments, the EO blend of lemongrass and cinnamon bark expressed spatial repellency towards the cool weather mosquito, Culiseta incidens (Thomson) (Diptera: Culicidae), even when this blend was disseminated from devices as much as 1 m away from a sentinel trap releasing attractive vertebrate host odorants and CO2. Deployment of EOs as spatial repellents in small outdoor gatherings could help protect humans from mosquito-borne diseases, particularly when this tactic is coupled with other tools of mosquito management.
Feeding Interactions Between Microorganisms and the House Dust Mites Dermatophagoides pteronyssinus and Dermatophagoides farinae (Astigmata: Pyroglyphidae)
Authors: Molva Vit , Nesvorna Marta , Hubert Jan
Published: May 2019

The feeding interactions between house dust mites (HDM) and microorganisms are key factors in the survival of mites in human environments. The suitability of different microbes for HDM is not known. Here, microbial species isolated from HDM cultures were offered to HDM in food preference tests under laboratory conditions. The microbial species were added to the rearing diet of mites to reach 7% of Saccharomyces cerevisiae and 10% of each tested microorganism. The suitability of each microbe-supplemented diet for Dermatophagoides pteronyssinus and Dermatophagoides farinae was compared in terms of mite population growth and mite preference in a cafeteria test. The effect of mite feeding on the respiration of microorganisms in the diet was observed in microcosms. HDM were able to feed and reproduce on some bacterial and fungal species, but the suitability of microbial species differed. Increasing the yeast Sa. cerevisiae in the diet from 7 to 17% appeared the most suitable for both mite species. Staphylococcus spp. bacteria were preferred for D. farinae and were suitable for reproduction. The population growth and feeding preferences of D. pteronyssinus and D. farinae with respect to microorganisms indicate that D. farinae can develop on a diet with bacterial (Staphylococcus nepalensis and Staphylococcus kloosii) additions, whereas D. pteronyssinus was successful on a diet with fungal (Aspergillus jensenii and Aspergillus ruber) additions. The bacteria Kocuria rhizophila and Bacillus cereus decreased population growth in D. pteronyssinus, whereas the yeasts Hyphopichia pseudoburtonii, Hyphopichia burtonii, and Candida ciferrii decreased population growth in D. farinae. These results indicate that some microorganisms are an important food source for HDM.
Effectiveness and Cost of Organized Outreach for Colorectal Cancer Screening: A Randomized, Controlled Trial
Authors: Somsouk Ma , Rachocki Carly , Mannalithara Ajitha , Garcia Dianne , Laleau Victoria , Grimes Barbara , Issaka Rachel B , Chen Ellen , Vittinghoff Eric , Shapiro Jean A , Ladabaum Uri
Published: May 2019

Background

Colorectal cancer (CRC) screening remains underused, especially in safety-net systems. The objective of this study was to determine the effectiveness, costs, and cost-effectiveness of organized outreach using fecal immunochemical tests (FITs) compared with usual care.

Methods

Patients age 50–75 years eligible for CRC screening from eight participating primary care safety-net clinics were randomly assigned to outreach intervention with usual care vs usual care alone. The intervention included a mailed postcard and call, followed by a mailed FIT kit, and a reminder phone call if the FIT kit was not returned. The primary outcome was screening participation at 1 year and a microcosting analysis of the outreach activities with embedded long-term cost-effectiveness of outreach. All statistical tests were two-sided.

Results

A total of 5386 patients were randomly assigned to the intervention group and 5434 to usual care. FIT screening was statistically significantly higher in the intervention group than in the control group (57.9% vs 37.4%, P < .001; difference = 20.5%, 95% confidence interval = 18.6% to 22.4%). In the intervention group, FIT completion rate was higher in patients who had previously completed a FIT vs those who had not (71.9% vs 35.7%, P < .001). There was evidence of effect modification of the intervention by language, and clinic. Outreach cost approximately $23 per patient and $112 per additional patient screened. Projecting long-term outcomes, outreach was estimated to cost $9200 per quality-adjusted life-year gained vs usual care.

Conclusion

Population-based management with organized FIT outreach statistically significantly increased CRC screening and was cost-effective in a safety-net system. The sustainability of the program and any impact of economies of scale remain to be determined.
Comparative Validation of Breast Cancer Risk Prediction Models and Projections for Future Risk Stratification
Authors: Pal Choudhury Parichoy , Wilcox Amber N , Brook Mark N , Zhang Yan , Ahearn Thomas , Orr Nick , Coulson Penny , Schoemaker Minouk J , Jones Michael E , Gail Mitchell H , Swerdlow Anthony J , Chatterjee Nilanjan , Garcia-Closas Montserrat
Published: May 2019

Background

External validation of risk models is critical for risk-stratified breast cancer prevention. We used the Individualized Coherent Absolute Risk Estimation (iCARE) as a flexible tool for risk model development and comparative model validation and to make projections for population risk stratification.

Methods

Performance of two recently developed models, one based on the Breast and Prostate Cancer Cohort Consortium analysis (iCARE-BPC3) and another based on a literature review (iCARE-Lit), were compared with two established models (Breast Cancer Risk Assessment Tool and International Breast Cancer Intervention Study Model) based on classical risk factors in a UK-based cohort of 64 874 white non-Hispanic women (863 patients) age 35–74 years. Risk projections in a target population of US white non-Hispanic women age 50–70 years assessed potential improvements in risk stratification by adding mammographic breast density (MD) and polygenic risk score (PRS).

Results

The best calibrated models were iCARE-Lit (expected to observed number of cases [E/O] = 0.98, 95% confidence interval [CI] = 0.87 to 1.11) for women younger than 50 years, and iCARE-BPC3 (E/O = 1.00, 95% CI = 0.93 to 1.09) for women 50 years or older. Risk projections using iCARE-BPC3 indicated classical risk factors can identify approximately 500 000 women at moderate to high risk (>3% 5-year risk) in the target population. Addition of MD and a 313-variant PRS is expected to increase this number to approximately 3.5 million women, and among them, approximately 153 000 are expected to develop invasive breast cancer within 5 years.

Conclusions

iCARE models based on classical risk factors perform similarly to or better than BCRAT or IBIS in white non-Hispanic women. Addition of MD and PRS can lead to substantial improvements in risk stratification. However, these integrated models require independent prospective validation before broad clinical applications.
The Pros and Cons of Incorporating Transcriptomics in the Age of Precision Oncology
Authors: Lin Victor T G , Yang Eddy S
Published: May 2019

The treatment of cancer continues to evolve toward personalized therapies based on individual patient and tumor characteristics. Our successes and failures in adopting a precision-oncology approach have demonstrated the utmost importance in identifying the proper predictive biomarkers of response. Until recently, most biomarkers were identified using immunohistochemistry for protein expression or single-gene analysis to identify targetable alterations. With the rapid propagation of next-generation sequencing to evaluate tumor tissue and “liquid biopsies,” identification of genomic biomarkers is now standard, particularly in non–small cell lung cancer, for which there is now an extensive catalog of biomarker-directed therapies with more anticipated to come. Despite these great strides, it has also become apparent that using genomic biomarkers alone will be insufficient, as it has been consistently shown that at least one-half of patients who undergo tumor genomic profiling have no actionable alteration. This is perhaps to be expected given the remarkable breadth of nongenetic factors that contribute to tumor initiation and progression. Some have proposed that the next logical step is to use transcriptome profiling to define new biomarkers of response to targeted agents. Recently, results from the WINTHER trial were published, specifically investigating the use of transcriptomics to improve match rates over genomic next-generation sequencing alone. In this review, we discuss the complexities of precision-oncology efforts and appraise the available evidence supporting the incorporation of transcriptomic data into the precision-oncology framework in the historical context of the development of biomarkers for directing cancer therapy.
Hydrologic balance, net primary productivity and water use efficiency of the introduced exotic Eucalyptus grandis × Eucalyptus urophylla plantation in south-western China
Authors: Hu Yanting , Zhao Ping , Huang Yuqing , Zhu Liwei , Ni Guangyan , Zhao Xiuhua , Huang Zhihong
Published: May 2019

Aims

Land cover changes can disrupt water balance and alter the partitioning of precipitation into surface runoff, evapotranspiration and groundwater recharge. The widely planted Eucalyptus trees in south-western China have the potential to bring about hydrologic impacts. Our research aims to elucidate the hydrologic balance characteristics of the introduced exotic Eucalyptus grandis × Eucalyptus urophylla plantation and to assess whether its high productivity results from high water use efficiency (WUE) or large water consumption.

Methods

A 400-m2 experimental plot was established in an E. grandis × E. urophylla plantation in south-western China. Water balance components, including stand transpiration (Tr), evapotranspiration (Et) and runoff (R) were obtained as follows: Tr was estimated based on sap flow measurements, Et was estimated as the average of surface transpiration and evaporation weighted by the fractional green vegetation cover using a modeling approach, and R was collected using the installed metal frame. Net primary productivity (NPP) was obtained from allometric equation and annual diameter at breast height (DBH) increment determination.

Important Findings

Annual Et and Tr were 430 ± 31 and 239 ± 17 mm, respectively. Annual Tr accounts for 56 ± 8% of total evapotranspiration on average. WUE (NPP/Tr) of the E. grandis × E. urophylla was estimated to be 3.3–3.9 mmol·mol−1. Based on the comparative analysis of Tr and WUE, E. grandis × E. urophylla had a high productivity due to its high WUE without exhibiting prodigal water use. Meteorological factors including vapor pressure deficit and global solar radiation (Rs) were key factors regulating Et and Tr in our research site. Annual surface runoff, Et and canopy interception occupied 7%, 27–30% and 16% of total precipitation, while the remaining 46–50% of precipitation was used for sustaining groundwater recharge and altering soil water storage. The higher runoff coefficient (7.1%) indicated the weaker capability of E. grandis × E. urophylla to reserve water resource than natural forests and less disturbed plantations. The planting and protection of understory vegetation may decrease the surface runoff and exert beneficial effects on water conservation capacity of Eucalyptus plantation.
Reading Jeremiah 52 in Exile: Purpose in the Composition of Jeremiah
Authors: Harger Adam K
Published: May 2019

Jeremiah 52 is valued among scholars for the insight it provides into the composition history of the larger book and its relationship to 2 Kings. Beyond the text-critical clues it provides, however, little is said about the relationship of Jeremiah 52 to the rest of the book. The chapter has been added to Jeremiah from its original position in 2 Kings 24–5 (or a common source), but it has been edited in the process. What follows is an exploration of a possible motivation for the addition of Jeremiah 52 to the larger book. Using the characters of Jehoiachin and Zedekiah as representatives of those who did and did not listen to the exhortation of the prophet, the editor uses the material of Jeremiah 52 to indicate that any future for the nation of Israel was located in—and would come out of—Babylon.
Goal Consensus and Collaboration
Authors: Tryon Georgiana Shick , Birch Sarah E. , Verkuilen Jay
Published: May 2019

This chapter provides meta-analyses of the relation between goal consensus and collaboration and individual psychotherapy outcome. For the 54 studies (N = 7,278) of goal consensus and outcome, the result was r = .24 or d = .49, representing a medium effect. For the 53 studies (N = 5,286) of patient–therapist collaboration and outcome, the result was r = .29 or d = .61, another medium effect. Results suggest patient–therapist goal consensus and collaboration enhance psychotherapy outcome. The chapter concludes with research limitations, diversity considerations, and therapeutic practices. Research suggests that therapists seek input from patients to form and effect treatment goals and plans, provide patients with regular feedback, and seek their involvement throughout therapy.
What Works in the Psychotherapy Relationship: Results, Conclusions, and Practices
Authors: Norcross John C. , Lambert Michael J.
Published: May 2019

This chapter concludes the first volume of the third edition of Psychotherapy Relationships That Work. The authors present the formal conclusions and the 28 recommendations of the Third Interdivisional Task Force. Summaries of the meta-analytic associations between the relationship elements and psychotherapy outcomes are provided. Those statements, approved by the 10 members of the Steering Committee, refer to the work in both this volume on therapy relationships and the second volume on treatment adaptations or relational responsiveness. These statements reaffirm and, in several instances, extend those of the earlier task forces. The chapter concludes with final thoughts on what works, and what does not, in the therapy relationship.
Cultural Adaptations and Multicultural Competence
Authors: Soto Alberto , Smith Timothy B. , Griner Derek , Rodríguez Melanie Domenech , Bernal Guillermo
Published: May 2019

Mental health treatments can be more effective when they align with the culture of the client and when therapists demonstrate multicultural competence. This chapter defines cultural adaptations and therapist multicultural competencies and provides clinical examples of each. It summarizes relevant research findings in two meta-analyses. In the meta-analysis on the effectiveness of culturally adapted interventions, the average effect size across 99 studies was d = .50. In the second meta-analysis on 15 studies of therapist cultural competence, the results differed by rating source: Client-rated measures of therapist cultural competence correlated strongly with treatment outcomes (r = .38) but therapists’ self-rated competency did not (r = .06). The chapter lists limitations of the research and patient contributions, concluding with research-supported therapeutic practices that help clients benefit from cultural adaptations and from therapists they perceive as culturally competent.
What Is a Concussion?
Authors: Brody David L.
Published: May 2019

A concussion is a traumatic brain injury, but not an immediately life-threatening one. A traumatic brain injury means that a sudden force has been applied to the brain from outside. But not every force causes a concussion. In fact, most do not. The scalp, skull, and dura do a pretty good job protecting our brains from most of what happens to us on a daily basis. A traumatic brain injury means that the force applied to the brain caused a disruption in the brain’s structure, an impairment of the brain’s function, or both. Just because a computed tomography (CT) scan, a magnetic resonance imaging (MRI) scan, or a blood test is negative does not mean that there has not been a concussion. Traumatic brain injury, especially concussion, is a clinical diagnosis, not based on any laboratory test or scan. Typically, patients with concussion have Glasgow Coma Scores between 13 and 15.
How Do You Make the Diagnosis of Concussion?
Authors: Brody David L.
Published: May 2019

To make a diagnosis of concussion, you need a reliable history of 2 things: (1) An acute external physical force applied to the brain AND (2) An impairment in the function of the brain directly caused by the external physical force. One or the other is not enough. You need both. You do not need a scan or lab test to make the diagnosis. No scan or test can “rule in” or “rule out” concussion. You do not need to perform a detailed neurological exam to make the diagnosis. The neurological exam is usually unremarkable except for immediately after the concussion. No exam findings “rule in” or “rule out” concussion.

A collateral source is key to obtaining a reliable history. The impairment in brain function occurs immediately after the event. The impairment is worst immediately after the event, then gradually improves. There is no other obvious explanation for the impairment.
Attention Deficit
Authors: Brody David L.
Published: May 2019

Many concussion patients who complain about problems with memory actually have an attention deficit. General measures: treat insomnia, stop alcohol, treat migraine with cogniphobia, prescribe moderate cardiovascular exercise, and refer for cognitive rehabilitation (occupational and speech therapy). Consider treatment with a stimulant such as methylphenidate (Ritalin) or amphetamine mixed salts (Adderall) if appropriate with careful monitoring for side effects. Contraindications include uncontrolled seizures, dangerous anxiety, active cardiovascular or cerebrovascular disease, active psychosis, drug abuse, irresponsible criminal behavior, dangerously underweight, and uncontrolled headaches. Recommend use 6 days per week 51 weeks per year to reduce tolerance. Additional benefit in some patients from donepezil (Aricept), rivastigmine (Exelon), and regulated caffeine use. Approach options: “aggressive” involving treatment with stimulants primarily based on history, “moderate” involving treatment with stimulants only in patients with attention performance impairments documented with neuropsychological evaluation, and “conservative” not including stimulants unless there is a well-documented preinjury history of attention deficit disorder.
Mood Instability and Irritability
Authors: Brody David L.
Published: May 2019

Often the complaint of mood instability comes from the collateral source. First priority: assess safety. Severe mood instability can lead to suicide. Next, determine whether the problem is actually mood instability, as opposed to sustained major anxiety, depression, or post-traumatic stress disorder. Nonpharmacological interventions are the most important, and include education, sleep management, prescription for cardiovascular exercise, pain control, cessation of alcohol and other disinhibiting substances, such as levetiracetam and cognitive behavioral therapy. Preferred pharmacological options that do not substantially impair cognitive recovery include lamotrigine (Lamictal) and oxcarbazepine (Trileptal). Other options include carbamazepine (Tegretol) when cost is an issue, propranolol (Inderal) when violence is a concern, and low-dose atypical antipsychotics.
Personality Change
Authors: Brody David L.
Published: May 2019

Most common concerns include mood instability, depression with loss of interests and pleasures, fatigue, loss of social intelligence, or other changes in interpersonal style. Treat pain aggressively, because uncontrolled pain may be a major factor. Treat any mood instability, depression, fatigue, or loss of social intelligence. For loss of social intelligence, refer to a trained psychologist with expertise in social intelligence, and to an occupational performance center, if available, for rehabilitation of social pragmatics in a group setting. For impairing changes in interpersonal style, refer to a psychologist with expertise in personality disorders. If the personality change is not causing significant problems, it is usually sufficient to educate the patient and family that personality commonly changes after brain injury, and that changes do not seem to be a problem at the moment.
Balance Problems
Authors: Brody David L.
Published: May 2019

Balance problems after concussion can be episodic or persistent. Episodic balance impairment due to intoxication by medications/alcohol/or other drugs can be treated by stopping the offending substance. Episodic balance impairment due to concussion-related benign paroxysmal positional vertigo can be treated with repositioning maneuvers. Assess for this using the Dix-Hallpike maneuvers. Episodic balance impairment due to migraine aura (even without actual headache) can be treated with migraine abortive medications and/or prophylactics. For persistent balance impairments, assess balance using the Balance Error Scoring System or Berg Balance Test. Advise patients to stop drinking alcohol, or to cut down to a maximum of 1 alcoholic drink in any 24-hour period, and, if possible, to stop medications that impair balance. Consider referral to physical therapy for balance training. Consider prescribing additional self-directed balance exercises such as tai chi, yoga, dance, etc. Emphasize that balance training is also part of preventing future concussions.
Memory Impairment
Authors: Brody David L.
Published: May 2019

Many complaints of memory problems after concussion actually turn out to be attention deficit. Take a careful collateral history regarding memory function in everyday life. Consider both bedside testing and formal neuropsychological testing of memory, but treat the patient not the test results. Reduce barriers to optimal memory function: Optimize sleep; treat chronic pain; taper or stop cognitively impairing medications; stop alcohol and illicit drugs; prescribe moderate cardiovascular exercise; test for vitamin B12 deficiency, hypothyroidism, electrolyte disorders, hypo- or hyperglycemia, renal failure, liver failure, and anemia. Refer to speech therapy and occupational therapy for memory training. Computer-based training can be beneficial in addition to in-person training. Stimulants can allow more intense cognitive rehabilitation when attention or fatigue are limiting. Consider pharmacological enhancers of memory including caffeine, donepezil, or rivastigmine. These have modest benefits and the nonpharmacological interventions are more important.
Return to Work
Authors: Brody David L.
Published: May 2019

Return-to-work planning is complex and requires individualized assessments. The patient should receive optimal treatment for headaches, sleep disorders, fatigue, anxiety, depression, mood instability, and attention deficit. An occupational therapist should try to simulate the patient’s workplace or most important work-related tasks to see how the patient performs, then attempt to develop compensatory strategies. Be more conservative with patients in high-risk occupations. Communicate directly with the patient’s supervisor to fully understand the nature of the work and whether there are lower-risk “light-duty” options possible. Advise patients in high cognitive demand professions not to make major decisions or take on any major new responsibilities during the rehabilitation process.