bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative Review of Genetic Factors Influencing Neurodevelopmental Outcomes in Preterm Infants
Authors: Blair Lisa M. , Pickler Rita H. , Anderson Cindy
Published: September 2015

Preterm infants are at elevated risk for a host of neurodevelopmental problems, including disorders that appear later in life. Gene–environment interactions and prematurity may combine to increase the risk for poor neurodevelopmental outcomes. Increasing evidence supports a genetic link to risk for atypical development; however, no genomic risk profiles are currently used for infants without apparent genetic disorders. The purpose of this review was to synthesize recent evidence of genetic associations with atypical neurodevelopmental outcomes that may affect preterm infants who do not have a rare genetic disease. Electronic and hand-search strategies were used to find relevant articles that were English-language, peer-reviewed primary research or meta-analysis reports published between July 2009 and July 2014, involving human participants. Articles included in the analysis ( N = 29) used a wide range of study designs and methodologies, complicating the analysis. An integrative-review design was used to synthesize the data. Numerous genes ( n = 43) and additional large deletion copy number variants were associated with neurodevelopmental outcomes, including cognition, attention, perception, psychiatric disease, autism spectrum disorder, cerebral palsy, infant behavior, and alterations in brain architecture. The creation of genetic risk profiles for complex disorders of neurodevelopment is presently hindered by inconsistent genetic-association evidence, methodological considerations, reporting problems, and lack of replication. However, several avenues of investigation offer promise, including large (>100 kb) copy number variants and the candidate genes MET, NRG3, and SLC6A4, each of which were reported to have associations with neurodevelopmental outcomes in multiple, high-quality studies.
The activation of grammaticalized meaning in L2 processing: Toward an explanation of the morphological congruency effect
Authors: Jiang Nan , Hu Guiling , Chrabaszcz Anna , Ye Lijuan
Published: September 2015

Objectives:

The study was intended to test the hypothesis that L2 speakers have difficulty in automatically activating a grammaticalized L2 meaning that is not morphologically marked in L1.

Methodology:

The study consisted of three experiments. A sentence–picture matching task was designed to assess the activation of grammaticalized meaning. The participants were asked to judge if a sentence correctly described the physical relationships of three objects in a picture. Hidden in the stimuli that required a positive response was a number agreement manipulation whereby a noun phrase in the sentence may agree or disagree with the number of objects in the picture. A number disagreement effect, as shown in a delay in producing a positive response on items of number disagreement was used to assess automatic activation of number meanings.

Data and Analysis:

The data constituted reaction times and accuracy rates from 32 English native speakers, 36 Chinese native speakers, 54 Chinese–English bilinguals, and 26 Russian–English bilinguals. Analyses of variance were performed in analyzing these data.

Findings:

The results showed a number disagreement effect in L1 and L2 among Russian English as a second language (ESL) speakers only. Chinese ESL speakers showed no difference between the two critical conditions in either language. A follow-up experiment showed that Chinese ESL speakers had no difficulty in automatically activating number meanings which were expressed lexically in English sentence processing. These findings provided support for the idea that the well documented difficulty L2 learners have in learning incongruent L2 inflectional morphemes may have to do with their difficulty in automatically activating a grammaticalized meaning that is not grammaticalized in their L1.

Originality:

The sentence–picture matching task represented a unique and effective approach to the study of the activation of grammaticalized meanings.

Significance:

The findings from the study represented some first psycholinguistic evidence regarding the activation of grammaticalized meanings among non-native speakers.
Directionality of cross-linguistic influence: Which referring choices do bilingual Ukrainian–English children make?
Authors: Mykhaylyk Roksolana , Ytterstad Elinor
Published: September 2015

Aims and research questions:

This paper presents a new study addressing the issue of cross-linguistic influence in acquisition of referring expressions. The main research question is how to predict directionality of this influence in a dual language development.

Methodology:

The method is an elicited production task. We consider the phenomenon of direct object referring choices, i.e. noun, pronoun and null element, in a ‘null-object’–‘overt-object’ language pair (Ukrainian and English).

Data and Analysis:

Participants of the experiment are 4–6-year-old Ukrainian–English bilinguals (N20) and Ukrainian monolinguals (N21). The data are analyzed in the statistical program R, utilizing the R-library function lme4. The results are presented as odds ratios (ORs) of each direct object type.

Findings:

Our data reveal that while there is no significant difference in Ukrainian object types in most of the age groups, there is a considerable amount of null object usage in English at the ages of four to five.

Originality:

The innovative nature of this study lies in: (i) the consideration of a licit object omission at a later stage of language development (from 4 to 6 years of age); (ii) the examination of an under-investigated language combination (i.e. English and Ukrainian); and (iii) the innovative approach to linguistic data analysis (e.g. comparing OR values).

Implications:

Our findings suggest that the directionality of influence in dual language acquisition depends on the developmental stage, language-specific means of syntax–pragmatics interaction, and extra-linguistic input-related factors. At the early stages of development, the null-object language is likely to influence the overt-object language, especially under conditions of limited exposure to the latter.
New spaces of development partnership: Rethinking international volunteering
Authors: Schech Susanne , Mundkur Anuradha , Skelton Tracey , Kothari Uma
Published: September 2015

The concept of partnership is frequently invoked in international development as discourse and policy prescription to better understand relationships and engagements between donors and beneficiaries. Despite the increasing prominence of the idea of partnerships, in reality mutual, equal and sustainable development partnerships remain limited. This article examines the extent to which recent growth in international development volunteering can provide new spaces where equitable and sustainable partnerships may emerge. This review highlights partnership’s legacy in discourses of participation and explores the changing role and impact of development volunteering. We identify three spaces where new kinds of alliances and relationships can be forged – personal learning, policy and geopolitical.
Book review: Economy, E.C. and Levi, M. 2014: By All Means Necessary: How China’s Resource Quest Is Changing the World
Authors: Baruah Nisha
Published: September 2015

Economy, E.C. and Levi, M. 2014: By All Means Necessary: How China’s Resource Quest Is Changing the World. New York: Oxford University Press. x + 279 pp. £18.99 hardback, $27.95 paperback. ISBN: 978-0-19-992178-2 (hardback). ISBN: 978-0-19-992178-2 (paperback).
Book review: McCowan, T. and Unterhalter, E., editors, 2015: Education and International Development: An Introduction
Authors: Channa Anila
Published: September 2015

McCowan, T. and Unterhalter, E., editors, 2015: Education and International Development: An Introduction. London: Bloomsbury Academic. xv + 386 pp. £75.00 cloth. £24.99 paper. ISBN: 978-1-4725-1100-3 (cloth), 978-1-4725-0697-9 (paper).
Book review: O’Brien, K., Clair, A.L.S. and Kristoffersen, B., editors, 2010: Climate Change, Ethics and Human Security
Authors: Lewis Nando
Published: September 2015

O’Brien, K., Clair, A.L.S. and Kristoffersen, B., editors, 2010: Climate Change, Ethics and Human Security. Cambridge University Press. xiv + 231 pp. £84.99 cloth. £26.99 paper. ISBN: 978-0-521-19766-3 (cloth), 978-1-107-69585-6 (paper).
Cognitive function in idiopathic pulmonary fibrosis
Authors: Bors Melinda , Tomic Rade , Perlman David M , Kim Hyun J , Whelan Timothy PM
Published: September 2015

The purpose of this study was to investigate whether there is evidence that individuals with severe idiopathic pulmonary fibrosis (IPF) have cognitive deficits when compared to individuals with healthy lungs. Participants completed five neuropsychological tests: Trail Making Test (TMT) A and B, Stroop Color Word Test (1, 2, 3), Hopkins Verbal Learning Test, Boston Naming Test, and Grooved Pegboard Test, additionally, the short form-36 and Beck Depression Index. Twelve participants (7 male, mean age 69.3, 9.4 years) comprised the severe IPF group defined by a diffusion capacity for carbon monoxide (DLCO) <30%. Thirty-four patients (22 male, mean age 63.2, 9.6 years) comprised the mild-to-moderate group with a DLCO >30%. Participating spouses ( n = 15, 4 male) served as the control group and had a mean age of 66.0, 10.8 years. Controlling for gender and age, the severe group had a significantly longer mean TMT B time (69.4, 135.9 seconds) than the mild group and the control group (86.7 seconds vs 83.2 seconds; p = 0.004 and 0.008 respectively), suggesting inferior performance on tasks requiring speed divided attention. In addition, the severe group had a significantly lower number of correctly identified colors in the Stroop 3 test (22.4 vs 30.6 vs 38.6; p < 0.001), suggesting slower processing speeds when requiring suppression of a familiar response. Participants with severe IPF had worse cognitive function than mild IPF or control subjects. Further research is needed to explain these findings and to develop interventions tailored to address these deficits.
Physical activity levels improve following discharge in people admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease
Authors: Tsai Ling Ling Y , Alison Jennifer A , McKenzie David K , McKeough Zoe J
Published: September 2015

This study aimed to determine the physical activity level of people admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and whether physical activity changed immediately after discharge and 6 weeks post hospital admission. In this prospective observational study, people admitted to hospital with an AECOPD had physical activity levels monitored using the SenseWear® Armband (model MF-SW) for 3 days in hospital (T1), during the first week at home following discharge (T2), and at home during the sixth week after admission (T3). Fifty participants (mean age (SD) 71 (10) years) completed the study. There was a linear increase in average steps per day over the three time periods (T1, mean (SD) 1385 (1972) steps/day; T2, 2040 (2680); T3, 2328 (2745); analysis of variance (ANOVA) p = 0.001) and time spent in moderate activity (3.0–6.0 metabolic equivalents; minutes/day) (T1, mean (SD) 16 (27) minutes/day; T2, 32 (46) minutes/day; T3, 35 (58) minutes/day; ANOVA p = 0.008). For both outcomes, post hoc t-tests showed significant improvements from T1 to T2 and from T1 to T3, but not between T2 and T3. Physical activity was low in hospital and significantly improved in the week after discharge but showed no further significant improvement at 6 weeks following a hospitalized AECOPD.
Arterial Embolisms and Thrombosis in Upper Extremity Ischemia
Authors: Skeik Nedaa , Soo-Hoo Sarah S. , Porten Brandon R. , Graber John , Alden Peter , Cragg Andrew , Alexander Jason Q. , Rizvi Adnan , Manunga Jesse M. , Garberich Ross F. , Sullivan Timothy
Published: September 2015

Objective:

Upper extremity ischemia (UEI) is an uncommon condition that can lead to permanent disability. There is a limited understanding of the etiology, management, and outcomes of the disease.

Methods:

We retrospectively reviewed the charts of all patients who were diagnosed with “embolism and/or thrombosis of arteries of upper extremity” at our institution from January 2005 to December 2013.

Results:

Patients diagnosed with embolisms were older ( P < .001), more likely to undergo thromboembolectomy ( P < .001), had higher rates of hypertension ( P = .001), and had longer lengths of hospital stay ( P = .002). There were no significant differences in complications or mortality at 30 days and up to 1 year.

Conclusion:

At our center, embolism was found to be the most common etiology for UEI followed by thrombosis and stenosis. Patients presented with embolism were older, were more likely to undergo thromboembolectomy, and had higher rates of hypertension and longer hospital stays.
Open Versus Endovascular Repair of Inflammatory Abdominal Aortic Aneurysms
Authors: Kakkos Stavros K. , Papazoglou Konstantinos O. , Tsolakis Ioannis A. , Lampropoulos George , Papadoulas Spyros I. , Antoniadis Pavlos N.
Published: September 2015

Objectives:

Open surgical repair (OSR) of inflammatory abdominal aortic aneurysms (IAAAs) can have significant morbidity. The aim of the present investigation was to compare IAAA outcome after OSR and endovascular aneurysm repair (EVAR) and perform a meta-analysis of the literature.

Methods:

Twenty-seven patients with an intact IAAA operated on during a 21-year period were included.

Results:

Nine patients were managed with EVAR and 18 with OSR. In the EVAR group, the number of transfused red blood cell units ( P = .001), procedure duration ( P < .001), and postoperative hospitalization ( P = .004) were significantly reduced compared to OSR. A trend for decreased morbidity with EVAR (11% vs 33% for OSR, P = .36) was observed. On literature review and meta-analysis, morbidity after EVAR was 8.3%, significantly lower compared to OSR (27.4%, P = .047). Mortality for nonruptured IAAAs was 0% after EVAR and 3.6% after OSR ( P = 1.00).

Conclusions:

Endovascular aneurysm repair of IAAAs is associated with decreased procedure duration, transfusion needs, hospitalization, and morbidity compared to OSR.
All in the Blood
Authors: Kowal Emma , Greenwood Ashley , McWhirter Rebekah E.
Published: September 2015

Public participation in medical research and biobanking is considered key to advances in scientific discovery and translation to improved health care. Cultural concerns relating to blood have been found to affect the participation of indigenous peoples and minorities in research, but such concerns are rarely specified in the literature. This article presents a review of the role of blood in Australian Aboriginal cultures. We discuss the range of meanings and uses of blood in traditional culture, including their use in ceremonies, healing, and sorcery. We draw on more recent literature on Aboriginal Australians and biomedicine to consider how traditional beliefs may be changing over time. These findings provide an empirical basis for researchers and bioethicists to develop culturally grounded strategies to boost the participation of Aboriginal Australians in biomedical research. They also serve as a model for integrating anthropological literature with bioethical concerns that could be applied to other indigenous and minority groups.
Oversight on the borderline: Quality improvement and pragmatic research
Authors: Finkelstein Jonathan A , Brickman Andrew L , Capron Alexander , Ford Daniel E , Gombosev Adrijana , Greene Sarah M , Iafrate R Peter , Kolaczkowski Laura , Pallin Sarah C , Pletcher Mark J , Staman Karen L , Vazquez Miguel A , Sugarman Jeremy
Published: September 2015

Pragmatic research that compares interventions to improve the organization and delivery of health care may overlap, in both goals and methods, with quality improvement activities. When activities have attributes of both research and quality improvement, confusion often arises about what ethical oversight is, or should be, required. For routine quality improvement, in which the delivery of health care is modified in minor ways that create only minimal risks, oversight by local clinical or administrative leaders utilizing institutional policies may be sufficient. However, additional consideration should be given to activities that go beyond routine, local quality improvement to first determine whether such non-routine activities constitute research or quality improvement and, in either case, to ensure that independent oversight will occur. This should promote rigor, transparency, and protection of patients’ and clinicians’ rights, well-being, and privacy in all such activities. Specifically, we recommend that (1) health care organizations should have systematic policies and processes for designating activities as routine quality improvement, non-routine quality improvement, or quality improvement research and determining what oversight each will receive. (2) Health care organizations should have formal and explicit oversight processes for non-routine quality improvement activities that may include input from institutional quality improvement experts, health services researchers, administrators, clinicians, patient representatives, and those experienced in the ethics review of health care activities. (3) Quality improvement research requires review by an institutional review board; for such review to be effective, institutional review boards should develop particular expertise in assessing quality improvement research. (4) Stakeholders should be included in the review of non-routine quality improvement and quality improvement–related research proposals. Only by doing so will we optimally leverage both pragmatic research on health care delivery and local implementation through quality improvement as complementary activities for improving health.
Harmonization and streamlining of research oversight for pragmatic clinical trials
Authors: O’Rourke P Pearl , Carrithers Judith , Patrick-Lake Bray , Rice Todd W , Corsmo Jeremy , Hart Raffaella , Drezner Marc K , Lantos John D
Published: September 2015

The oversight of research involving human participants is a complex process that requires institutional review board review as well as multiple non-institutional review board institutional reviews. This multifaceted process is particularly challenging for multisite research when each site independently completes all required local reviews. The lack of inter-institutional standardization can result in different review outcomes for the same protocol, which can delay study operations from start-up to study completion. Hence, there have been strong calls to harmonize and thus streamline the research oversight process. Although the institutional review board is only one of the required reviews, it is often identified as the target for harmonization and streamlining. Data regarding variability in decision-making and interpretation of the regulations across institutional review boards have led to a perception that variability among institutional review boards is a primary contributor to the problems with review of multisite research. In response, many researchers and policymakers have proposed the use of a single institutional review board of record, also called a central institutional review board, as an important remedy. While this proposal has merit, the use of a central institutional review board for multisite research does not address the larger problem of completing non-institutional review board institutional review in addition to institutional review board review—and coordinating the interdependence of these reviews. In this article, we describe the overall research oversight process, distinguish between institutional review board and institutional responsibilities, and identify challenges and opportunities for harmonization and streamlining. We focus on procedural and organizational issues and presume that the protection of human subjects remains the paramount concern. Suggested modifications of institutional review board processes that focus on time, efficiency, and consistency of review must also address what effect such changes have on the quality of review. We acknowledge that assessment of quality is difficult in that quality metrics for institutional review board review remain elusive. At best, we may be able to assess the time it takes to review protocols and the consistency across institutions.
Harms, benefits, and the nature of interventions in pragmatic clinical trials
Authors: Ali Joseph , Andrews Joseph E , Somkin Carol P , Rabinovich C Egla
Published: September 2015

To produce evidence capable of informing healthcare decision making at all critical levels, pragmatic clinical trials are diverse both in terms of the type of intervention (medical, behavioral, and/or technological) and the target of intervention (patients, clinicians, and/or healthcare system processes). Patients and clinicians may be called on to participate as designers, investigators, intermediaries, or subjects of pragmatic clinical trials. Other members of the healthcare team, as well as the healthcare system itself, also may be affected directly or indirectly before, during, or after study implementation. This diversity in the types and targets of pragmatic clinical trial interventions has brought into focus the need to consider whether existing ethics and regulatory principles, policies, and procedures are appropriate for pragmatic clinical trials. Specifically, further examination is needed to identify how the types and targets of pragmatic clinical trial interventions may influence the assessment of net potential risk, understood as the balance of potential harms and benefits. In this article, we build on scholarship seeking to align ethics and regulatory requirements with potential research risks and propose an approach to the assessment of net risks that is sensitive to the diverse nature of pragmatic clinical trial interventions. We clarify the potential harms, burdens, benefits, and advantages of common types of pragmatic clinical trial interventions and discuss implications for patients, clinicians, and healthcare systems.
Considerations in the evaluation and determination of minimal risk in pragmatic clinical trials
Authors: Lantos John D , Wendler David , Septimus Edward , Wahba Sarita , Madigan Rosemary , Bliss Geraldine
Published: September 2015

Institutional review boards, which are charged with overseeing research, must classify the riskiness of proposed research according to a federal regulation known as the Common Rule (45 CFR 46, Subpart A) and by regulations governing the US Food and Drug Administration codified in 21 CFR 50. If an institutional review board determines that a clinical trial constitutes “minimal risk,” there are important practical implications: the institutional review board may then allow a waiver or alteration of the informed consent process; the study may be carried out in certain vulnerable populations; or the study may be reviewed by institutional review boards using an expedited process. However, it is unclear how institutional review boards should assess the risk levels of pragmatic clinical trials. Such trials typically compare existing, widely used medical therapies or interventions in the setting of routine clinical practice. Some of the therapies may be considered risky of themselves but the study comparing them may or may not add to that pre-existing level of risk. In this article, we examine the common interpretations of research regulations regarding minimal-risk classifications and suggest that they are marked by a high degree of variability and confusion, which in turn may ultimately harm patients by delaying or hindering potentially beneficial research. We advocate for a clear differentiation between the risks associated with a given therapy and the incremental risk incurred during research evaluating those therapies as a basic principle for evaluating the risk of a pragmatic clinical trial. We then examine two pragmatic clinical trials and consider how various factors including clinical equipoise, practice variation, research methods such as cluster randomization, and patients’ perspectives may contribute to current and evolving concepts of minimal-risk determinations, and how this understanding in turn affects the design and conduct of pragmatic clinical trials.
Use of altered informed consent in pragmatic clinical research
Authors: McKinney Ross E , Beskow Laura M , Ford Daniel E , Lantos John D , McCall Jonathan , Patrick-Lake Bray , Pletcher Mark J , Rath Brian , Schmidt Hollie , Weinfurt Kevin
Published: September 2015

There are situations in which the requirement to obtain conventional written informed consent can impose significant or even insurmountable barriers to conducting pragmatic clinical research, including some comparative effectiveness studies and cluster-randomized trials. Although certain federal regulations governing research in the United States (45 CFR 46) define circumstances in which any of the required elements may be waived, the same standards apply regardless of whether any single element is to be waived or whether consent is to be waived in its entirety. Using the same threshold for a partial or complete waiver limits the options available to institutional review boards as they seek to optimize a consent process. In this article, we argue that new standards are necessary in order to enable important pragmatic clinical research while at the same time protecting patients’ rights and interests.
Ethical responsibilities toward indirect and collateral participants in pragmatic clinical trials
Authors: Smalley Jaye Bea , Merritt Maria W , Al-Khatib Sana M , McCall Debbe , Staman Karen L , Stepnowsky Carl
Published: September 2015

Pragmatic clinical trials are designed to inform decision makers about the benefits, burdens, and risks of health interventions in real-world settings. Pragmatic clinical trials often use for research purposes data collected in the course of clinical practice. The distinctive features of pragmatic clinical trials demand fresh thinking about what is required to act properly toward people affected by their conduct, in ways that go beyond ensuring the protection of rights and welfare for “human research subjects” under conventional research ethics regulations. To stimulate such work, we propose to distinguish among categories of research participants in pragmatic clinical trials as follows: Direct participants: (1) individuals being directly intervened upon and/or (2) individuals from whom personal identifiable data are being collected for the purposes of the pragmatic clinical trial. Indirect participants: individuals who are (1) not identified as direct participants and (2) whose rights and welfare may be affected by the intervention through their routine exposure to the environment in which the intervention is being deployed. Collateral participants: patient groups and other stakeholder communities who may be otherwise affected by the occurrence and findings of the pragmatic clinical trial. We illustrate these distinctions with case examples and discuss the distinctive responsibilities of researchers and pragmatic clinical trial leadership toward each type of participant. We suggest that pragmatic clinical trial investigators, institutional review boards, health systems leaders, and others engaged in the research enterprise work together to identify these participants. For indirect participants, risks and benefits to which they are exposed should be weighed to ensure that their rights and welfare are protected accordingly, and communication strategies should be considered to help them make well-informed decisions. Collateral participants could provide input on the design, planning, and conduct of a pragmatic clinical trial and offer insights regarding the best way to communicate the trial’s results to their constituencies.
Gatekeepers for pragmatic clinical trials
Authors: Whicher Danielle M , Miller Jennifer E , Dunham Kelly M , Joffe Steven
Published: September 2015

To successfully implement a pragmatic clinical trial, investigators need access to numerous resources, including financial support, institutional infrastructure (e.g. clinics, facilities, staff), eligible patients, and patient data. Gatekeepers are people or entities who have the ability to allow or deny access to the resources required to support the conduct of clinical research. Based on this definition, gatekeepers relevant to the US clinical research enterprise include research sponsors, regulatory agencies, payers, health system and other organizational leadership, research team leadership, human research protections programs, advocacy and community groups, and clinicians. This article provides a framework to help guide gatekeepers’ decision-making related to the use of resources for pragmatic clinical trials. Relevant ethical considerations for gatekeepers include (1) concern for the interests of individuals, groups, and communities affected by the gatekeepers’ decisions, including protection from harm and maximization of benefits; (2) advancement of organizational mission and values; and (3) stewardship of financial, human, and other organizational resources. Separate from these ethical considerations, gatekeepers’ actions will be guided by relevant federal, state, and local regulations. This framework also suggests that to further enhance the legitimacy of their decision-making, gatekeepers should adopt transparent processes that engage relevant stakeholders when feasible and appropriate. We apply this framework to the set of gatekeepers responsible for making decisions about resources necessary for pragmatic clinical trials in the United States, describing the relevance of the criteria in different situations and pointing out where conflicts among the criteria and relevant regulations may affect decision-making. Recognition of the complex set of considerations that should inform decision-making will guide gatekeepers in making justifiable choices regarding the use of limited and valuable resources.
The Food and Drug Administration and pragmatic clinical trials of marketed medical products
Authors: Anderson Monique L , Griffin Joseph , Goldkind Sara F , Zeitler Emily P , Wing Liz , Al-Khatib Sana M , Sherman Rachel E
Published: September 2015

Pragmatic clinical trials can help answer questions of comparative effectiveness for interventions routinely used in medical practice. Pragmatic clinical trials may examine outcomes of one or more marketed medical products, and they are heterogeneous in design and risk. The Food and Drug Administration is charged with protecting the rights, safety, and welfare of individuals enrolled in clinical investigations, as well as assuring the integrity of the data upon which approval of medical products is made. The Food and Drug Administration has broad jurisdiction over drugs and medical devices (whether or not they are approved for marketing), and as such, clinical investigations of these products are subject to applicable Food and Drug Administration regulations. While many pragmatic clinical trials will meet the criteria for an exemption from the requirements for an investigational new drug application or investigational device exemption, in general, all clinical investigations of medical products that fall under Food and Drug Administration jurisdiction must adhere to regulations for informed consent and review by an institutional review board. We are concerned that current Food and Drug Administration requirements for obtaining individual informed consent may deter or delay the conduct of pragmatic clinical trials intended to develop reliable evidence of comparative safety and effectiveness of approved medical products that are regulated by the Food and Drug Administration. Under current regulations, there are no described mechanisms to alter or waive informed consent to make it less burdensome or more practicable for low-risk pragmatic clinical trials. We recommend that the Food and Drug Administration establish a risk-based approach to obtaining informed consent in pragmatic clinical trials that would facilitate the conduct of pragmatic clinical trials without compromising the protection of enrolled individuals or the integrity of the resulting data.
The ethics and regulatory landscape of including vulnerable populations in pragmatic clinical trials
Authors: Welch Mary Jane , Lally Rachel , Miller Jennifer E , Pittman Stephanie , Brodsky Lynda , Caplan Arthur L , Uhlenbrauck Gina , Louzao Darcy M , Fischer James H , Wilfond Benjamin
Published: September 2015

Policies have been developed to protect vulnerable populations in clinical research, including the US federal research regulations (45 Code of Federal Regulations 46 Subparts B, C, and D). These policies generally recognize vulnerable populations to include pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons. The aim has been to protect these populations from harm, often by creating regulatory and ethical checks that may limit their participation in many clinical trials. The recent increase in pragmatic clinical trials raises at least two questions about this approach. First, is exclusion itself a harm to vulnerable populations, as these groups may be denied access to understanding how health interventions work for them in clinical settings? Second, are groups considered vulnerable in traditional clinical trials also vulnerable in pragmatic clinical trials? We argue first that excluding vulnerable subjects from participation in pragmatic clinical trials can be harmful by preventing acquisition of data to meaningfully inform clinical decision-making in the future. Second, we argue that protections for vulnerable subjects in traditional clinical trial settings may not be translatable, feasible, or even ethical to apply in pragmatic clinical trials. We conclude by offering specific recommendations for appropriately protecting vulnerable research subjects in pragmatic clinical trials, focusing on pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons.
Online leadership discourse in higher education: A digital multimodal discourse perspective
Authors: Tan Sabine , Smith Bradley A , O’Halloran Kay L
Published: September 2015

As leadership discourses in higher education are increasingly being mediated online, texts previously reserved for staff are now being made available in the public domain. As such, these texts become accessible for study, critique and evaluation. Additionally, discourses previously confined to the written domain are now increasingly multimodal. Thus, an approach is required that is capable of relating detailed, complex multimodal discourse analyses to broader sociocultural perspectives to account for the complex meaning-making practices that operate in online leadership discourses. For this purpose, a digital multimodal discourse approach is proposed and illustrated via a small-scale case study of the online leadership discourse of an Australian university. The analysis of two short video texts demonstrates how a digital multimodal discourse perspective facilitates the identification of key multimodal systems used for meaning-making in online communication, how meaning arises through combinations of semiotic choices (not individual choices), and how the results of multimodal discourse analysis using digital technology can reveal larger sociocultural patterns – in this case, divergent leadership styles and approaches as reflected in online discourse, at a time of immense change within the higher education sector.
Hexaminolevulinate hydrochloride in the detection of nonmuscle invasive cancer of the bladder
Authors: Di Stasi Savino M. , De Carlo Francesco , Pagliarulo Vincenzo , Masedu Francesco , Verri Cristian , Celestino Francesco , Riedl Claus
Published: September 2015

Clinical trials have shown that hexaminolevulinate (HAL) fluorescence cystoscopy improves the detection of bladder tumors compared with standard white-light cystoscopy, resulting in more efficacious treatment. However, some recent meta-analyses report controversially on recurrence-free rates with this procedure. A systematic review of literature was performed from December 2014 to January 2015 using the PubMed, Embase and Cochrane databases for controlled trials on photodynamic diagnosis (PDD) with HAL. A total of 154 publications were found up to January 2015. Three of the authors separately reviewed the records to evaluate eligibility and methodological quality of clinical trials. A total of 16 publications were considered eligible for analysis. HAL–PDD-guided cystoscopy increased overall tumor detection rate (proportion difference 19%, 95% confidence interval [CI] 0.152–0.236) although the benefit was particularly significant in patients with carcinoma in situ (CIS) lesion (proportion difference 15.7%, 95% CI 0.069–0.245) and was reduced in papillary lesions (Ta proportion difference 5.9%, 95% CI 0.014–0.103 and T1 proportion difference 1.2%, 95% CI 0.033–0.057). Moreover, there were 15% of patients (95% CI 0.098–0.211) with at least one additional tumor seen with PDD. With regard to recurrence rates, the data sample was insufficient for a statistical analysis, although the evaluation of raw data showed a trend in favor of HAL–PDD. This meta-analysis confirms the increased tumor detection rate by HAL–PDD with a most pronounced benefit for CIS lesion.
Reading Minds and Being Invisible
Authors: Howland Maryhope
Published: September 2015

Recent research suggests that social support is more beneficial when it is provided invisibly (subtly and without recipient awareness); however, what is still unknown is who is most likely to provide invisible support. The hypothesis that support providers exhibiting greater empathic accuracy are more likely to provide invisible support is tested in two studies of committed romantic couples: a month-long diary study in a highly stressful situation (Study 1, n = 311 couples) and an in-lab social observation study in which one member discusses a mildly stressful personal goal (Study 2, n = 85 couples). In Study 1, providers exhibiting greater empathic accuracy on a given day were more likely to provide invisible practical support the same day. In Study 2, providers’ empathic accuracy was positively associated with their provision of invisible practical support during the interaction (both coded by trained observers). Similar findings did not emerge for emotional support.
MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study
Authors: Copie-Bergman Christiane , Cuillière-Dartigues Peggy , Baia Maryse , Briere Josette , Delarue Richard , Canioni Danielle , Salles Gilles , Parrens Marie , Belhadj Karim , Fabiani Bettina , Recher Christian , Petrella Tony , Ketterer Nicolas , Peyrade Frederic , Haioun Corinne , Nagel Inga , Siebert Reiner , Jardin Fabrice , Leroy Karen , Jais Jean-Philippe , Tilly Herve , Molina Thierry Jo , Gaulard Philippe
Published: September 2015

Key Points

MYC-IG translocation partner gene is a negative predictor of survival in DLBCL patients.
Genetic and morphological evidence for introgression between three species of willows
Authors: Fogelqvist Johan , Verkhozina Alla V. , Katyshev Alexander I. , Pucholt Pascal , Dixelius Christina , Rönnberg-Wästljung Ann Christin , Lascoux Martin , Berlin Sofia
Published: September 2015

Background

Hybridization and introgression are said to occur relatively frequently in plants, and in particular among different species of willows. However, data on the actual frequency of natural hybridization and introgression is rare. Here, we report the first fine-scale genetic analysis of a contact zone shared between the three basket willow species,Salix dasyclados,S. schweriniiandS. viminalisin the vicinity of the Lake Baikal in Southern Siberia. Individuals were sampled in fourteen populations and classified as pure species or hybrids based on a set of morphological characters. They were then genotyped at 384 nuclear SNP and four chloroplast SSR loci. The STRUCTURE and NewHybrids softwares were used to estimate the frequency and direction of hybridization using genotypic data at the nuclear SNP loci.

Results

As many as 19 % of the genotyped individuals were classified as introgressed individuals and these were mainly encountered in the centre of the contact zone. All introgressed individuals were backcrosses toS. viminalisorS. schweriniiand no F1 or F2 hybrids were found. The rest of the genotyped individuals were classified as pure species and formed two clusters, one withS. schweriniiindividuals and the other withS. viminalisandS. dasycladosindividuals.The two clusters were significantly genetically differentiated, withFST = 0.333 (0.282–0.382,p < 0.001). In contrast, for the chloroplast haplotypes, no genetic differentiation was observed as they were completely shared between the species. Based on morphological classification only 5 % of the individuals were classified as introgressed individuals, which was much less than what was detected using genotypic data.

Conclusions

We have discovered a new willow hybrid zone with relatively high frequency of introgressed individuals. The low frequency of F1 hybrids indicates that ongoing hybridization is limited, which could be because of the presence of reproductive barriers or simply because the conditions are not favorable for hybridization. We further conclude that in order to get a complete picture of the species composition of a hybrid zone it is necessary to use a combination of morphological characters and genetic data from both nuclear and chloroplast markers.
Overseas Filipino workers in conflict zones: narratives of Filipino nurses in Libya
Authors: Vilog Ron Bridget T. , Ballesteros Marie Donna M.
Published: September 2015

This paper examines the risk perception of Filipino nurses who worked in Libya during the height of post-2011 crisis. The narratives reveal that Filipino nurses took advantage of the massive hiring campaign organized by Libya’s Ministry of Health in 2012, hoping that their migration experiences would result in economic and social rewards as they established their careers in the healthcare industry. After 2 years of adjustment to the conflict-ridden environment, they found themselves situated in another episode of civil war, once again defying the Philippine government’s mandatory repatriation program. Guided by Carretero’s (Risk-taking in unauthorised migration, 2008) thesis, we observed the mechanism of defiance that entails risk-taking as the political crisis loomed. Filipino nurses, especially those who initially refused to leave Libya, embraced an “illusion of control” that eventually reinforced an “unrealistic optimism.” These risk-minimizing strategies have successfully undermined the protective powers of the state. The paper argues that Filipino migrants in crisis zones like Libya undertake risk calculation and reduction, albeit with a tendency to commit risk denial and a false sense of empowerment and exceptionality. In the end, however, it is emphasized that these mechanisms have limitations, depending on the experiences, timing, and risk interpretation of the migrants.
The Effect of Federal Drug Law on the Incidence of Drug Abuse
Authors: Anthony James Christopher
Published: September 2015

The Controlled Substances Act (CSA) is the prevailing “drug abuse” control statute in the United States. Its manifest objective is to prevent or reduce drug use's “substantial and detrimental effect on the health and general welfare of the American people.” Evaluating CSA's effectiveness in 1975, a Domestic Council Task Force reported in a White Paper to President Gerald Ford that its control measures do “reduce abuse of dangerous drugs.” The Task Force's evidence was based upon a before-and-after analysis of the frequency of “drug abuse episodes” reported to the nation's Drug Abuse Warning Network (DAWN).

This research note challenges the conclusion of the Domestic Council Task Force, subjecting the DAWN evidence to more rigorous scrutiny, and concluding that we do not presently have adequate materials to assess whether CSA meets its health objectives. The context of this conclusion is that of drug control, but its implications apply to health policy and health policy evaluation in general.
Maximum Allowable Cost: Can the Government Control Drug Costs? A Retrospective Political Analysis of Events and Issues
Authors: Smith Michael Ira , Wertheimer Albert I.
Published: September 2015

In 1973 the federal government moved to limit drug reimbursement to providers in federally sponsored or supported programs, to the lowest cost at which the drug is generally and consistently available unless a difference in therapeutic effect can be demonstrated between the brand name and generic drug. This paper examines the political evolution and rationale for this program and explores the issues surrounding the ongoing controversy regarding publicly financed programs offering drug benefits.

The authors speculate that the government's first attempt to control prices of pharmaceuticals, prior to enactment of some form of national health insurance, if successful, will call forth pharmaceutical industry strategies which could negate program benefits.
Accountability in Health Care: An Essay on Mechanisms, Muddles, and Mires
Authors: Bjorkman James Warner , Altenstetter Christa
Published: September 2015

This paper presents a critical evaluation of several theories of accountability and their applicability to health care concerns. The authors first provide a preliminary refinement of the imprecise concept of accountability itself and then examine four major types (political; bureaucratic; professional; and economic-consumer). Then, by using disciplinary perspectives provided by several schools of thought in political science (legislative supremacy; general manager theory; government by bureaucracy; objective responsibility; citizen participation), they discuss the degree of accountability presently found in various American health policies. After identifying the inherent dilemmas within any credible accountability approach to health care programs as now utilized in the United States, the authors recommend that all types of accountability be integrated and strengthened by relying more explicitly on practices characteristic of development administration.
Diagnosis and the Dole: The Function of Illness in American Distributive Politics
Authors: Stone Deborah A.
Published: September 2015

This article argues that the concept of illness has certain properties that make it a convenient administrative device for managing a need-based redis-tributive system in a society whose primary distributive system is based on work. These properties—cultural acceptance of illness as a legitimate excuse for not working, objective standards for identifying illness, and restrictiveness—have led to the widespread use of illness as an eligibility criterion for many social benefits, including cash transfers, services, privileges and exemptions. Paradoxically, the traditional rationales for using illness as one of the keystones of categorical welfare policy are eroding, yet welfare programs based on illness certification are growing rapidly. To explain this anomaly, the author suggests that medical certification as a distributive mechanism serves certain latent political functions, such as allowing welfare programs to be responsive to political unrest, siphoning off opposition to controversial policies by the granting of medical exemptions to intense opponents, and reducing political conflict by using physicians as arbiters.