bluuebunny/crossref_metadata_2025 huggingface dataset:
Q‐learning residual analysis: application to the effectiveness of sequences of antipsychotic medications for patients with schizophrenia
Authors: Ertefaie Ashkan , Shortreed Susan , Chakraborty Bibhas
Published: January 2016

Q‐learning is a regression‐based approach that uses longitudinal data to construct dynamic treatment regimes, which are sequences of decision rules that use patient information to inform future treatment decisions. An optimal dynamic treatment regime is composed of a sequence of decision rules that indicate how to optimally individualize treatment using the patients' baseline and time‐varying characteristics to optimize the final outcome. Constructing optimal dynamic regimes using Q‐learning depends heavily on the assumption that regression models at each decision point are correctly specified; yet model checking in the context of Q‐learning has been largely overlooked in the current literature. In this article, we show that residual plots obtained from standard Q‐learning models may fail to adequately check the quality of the model fit. We present a modified Q‐learning procedure that accommodates residual analyses using standard tools. We present simulation studies showing the advantage of the proposed modification over standard Q‐learning. We illustrate this new Q‐learning approach using data collected from a sequential multiple assignment randomized trial of patients with schizophrenia. Copyright © 2016 John Wiley & Sons, Ltd.
European Imperialism, 1860-1914
Authors: Porter Andrew
Published: January 2016

This study surveys the growth of European intervention outside Europe between 1860 and 1914. It treats its subject, 'imperialism', as a process of increasing contact, influence and control, rather than as the nature and consequences of colonial rule. The problems of defining 'imperialism' are considered alongside various analytical approaches to the term. In examining the controversial historiographical literature surrounding this subject, the book criticises particular explanations, and introduces readers to some of the new directions in research and inquiry currently being explored by historians.
Strategien zur Vernetzung von Biobanken
Authors: Lablans Martin , Kadioglu Dennis , Mate Sebastian , Leb Ines , Prokosch Hans-Ulrich , Ückert Frank
Published: January 2016

Hintergrund

Nicht selten benötigt ein medizinisches Forschungsvorhaben mehr biologisches Material, als in einer einzigen Biobank verfügbar ist. Daher unterstützt eine Vielzahl von Strategien das Auffinden potentieller Forschungspartner mit passenden Proben, auch ohne dass diese zuvor in einer zentralisierten Sammlung zusammengeführt werden müssen.

Ziel

Der vorliegende Beitrag beschreibt die Klassifizierung verschiedener Strategien zur Vernetzung von Biomaterialbanken, speziell zur Probensuche, sowie eine IT-Infrastruktur, die diese Ansätze kombiniert.

Material und Methoden

Bestehende Strategien lassen sich nach drei Kriterien klassifizieren: a) Granularität der Probendaten: grobe Daten auf Bankebene (Katalog) vs. feingranulare Daten auf Probenebene, b) Speicherort der Probendaten: zentrale (zentraler Suchdienst) vs. dezentrale Datenhaltung (föderierte Suchdienste) und c) Automatisierungsgrad: automatisch (abfragebasiert, föderierter Suchdienst) vs. halbautomatisch (anfragebasiert, dezentrale Suche). Alle genannten Suchdienste setzen eine Datenintegration voraus; dabei helfen Metadaten bei der Überwindung semantischer Heterogenität.

Ergebnisse

Der „Common Service IT“ in BBMRI-ERIC („Biobanking and Biomolecular Resources Research Infrastructure-European Research Infrastructure Consortium“) vereint einen Katalog, die dezentrale Suche und Metadaten in einer integrierten Plattform, um Forschern vielseitige Werkzeuge zur Suche nach passendem Probenmaterial zu geben und bei den Biobankern gleichzeitig ein hohes Maß an Datenhoheit zu bewahren.

Diskussion

Trotz ihrer Unterschiede schließen sich die vorgestellten Strategien zur Vernetzung von Biomaterialbanken gegenseitig nicht aus. Vielmehr lassen sie sich in gemeinsamen Forschungsinfrastrukturen sinnvoll ergänzen und sie können sogar voneinander profitieren.
Comparison of Bilateral Axillo‐Breast Approach Robotic Thyroidectomy with Open Thyroidectomy for Graves’ Disease
Authors: Kwon Hyungju , Yi Jin Wook , Song Ra‐Yeong , Chai Young Jun , Kim Su‐jin , Choi June Young , Lee Kyu Eun
Published: January 2016

Background

There is an ongoing debate about whether robotic thyroidectomy (RT) is appropriate for Graves’ disease. The aim of this study was to compare the safety of bilateral axillo‐breast approach (BABA) RT with that of open thyroidectomy (OT) in patients with Graves’ disease.

Methods

From January 2008 to June 2014, 189 (44 BABA RT and 145 OT) patients underwent total thyroidectomy for Graves’ disease. Recurrence of Graves’ disease, intraoperative blood loss, hospital stay, and complication rates including recurrent laryngeal nerve (RLN) palsy and hypoparathyroidism were analyzed between BABA RT and OT groups, after propensity score matching according to age, gender, body mass index, surgical indication, the extent of operation, excised thyroid weight, and follow‐up period.

Results

No patient experienced recurrence of Graves’ disease after median follow‐up of 35.0 months. Intraoperative blood loss (151.8 ± 165.4 mL vs. 134.5 ± 75.4 mL; p = 0.534) and hospital stay (3.4 ± 0.7 day vs. 3.3 ± 0.7 day; p = 0.564) were not different between BABA RT and OT groups. Complication rates including transient RLN palsy (11.4 vs. 11.4 %; p = 1.000), transient hypoparathyroidism (18.2 vs. 20.5 %; p = 0.787), permanent RLN palsy (0 vs. 2.3 %; p = 0.315), and permanent hypoparathyroidism (2.3 vs. 2.3 %; p = 1.000) were also comparable between groups.

Conclusions

BABA RT for Graves’ disease showed comparable surgical completeness and complications to conventional OT. BABA RT can be recommended as an alternative surgical option for patients with Graves’ disease who are concerned about cosmesis.
At a Loss for Words: Measuring Racial Inequality in America
Authors: Coleman Major G.
Published: January 2016

Scholars of race tend to measure racial inequality in either absolute or relative terms. How much Blacks have advanced from their historical antebellum status is an absolute measure. How the status of Blacks compares with that of Whites is a relative measure. A more revealing measure might be how much racial equality will be strategically necessary to avoid a major politico-economic crisis like the ones that occurred during the civil war and the 1960s. Though it is easier to measure absolute or relative equality, measures of strategic equality yeild more important information. Using the Current Population Survey, General Social Survey, Center for Education Statistics, Multi-City Study of Urban Inequality, and Census Bureau estimates, I find that, strategically, America is actually declining in racial equality, not advancing.
The progress test of medicine: the Dutch experience
Authors: Tio René A. , Schutte Bert , Meiboom Ariadne A. , Greidanus Janke , Dubois Eline A. , Bremers Andre J. A. , Dutch Working Group
Published: January 2016

Progress testing in the Netherlands has a long history. It was first introduced at one medical school which had a problem-based learning (PBL) curriculum from the start. Later, other schools with and without PBL curricula joined. At present, approximately 10,000 students sit a test every three months. The annual progress exam is not a single test. It consists of a series of 4 tests per annum which are summative in the end. The current situation with emphasis on the formative and summative aspects will be discussed. The reader will get insight into the way progress testing can be used as feedback for students and schools.
The effect of constructing versus solving virtual patient cases on transfer of learning: a randomized trial
Authors: Tolsgaard Martin G. , Jepsen Rikke M.H.G. , Rasmussen Maria B. , Kayser Lars , Fors Uno , Laursen Lars C. , Svendsen Jesper H. , Ringsted Charlotte
Published: January 2016

The purpose of this study was to explore the effect of actively constructing virtual patient (VP) cases compared with solving VP cases on knowledge gains, skills transfer and time spent on cases. Forty-five fourth-year medical students were randomized to constructing (VP-construction, n = 23) or solving (VP-solving, n = 22) four cardiopulmonary VP cases. Whereas the VP-solving group solved the cases, the VP-construction group only received the final diagnosis and had to complete the history, physical findings, and lab results. After a week, participants completed a transfer test involving two standardized patients representing cardiopulmonary cases. Performances on the transfer test were video-recorded and assessed by two blinded raters using the Reporter, Interpreter, Manager, Educator (RIME) framework. Thirty-nine participants completed the transfer test. The VP-construction group spent significantly more time on the VP cases compared with the VP-solving group, p = 0.002. There were no significant differences in RIME scores between the VP-construction group and VP-solving group, p = 0.54.

In conclusion, engaging novice students in active VP case construction may be more time consuming than solving VP cases, without resulting in superior skills transfer.
Innovating the practice of medical speciality training
Authors: Fokkema Joanne P.I.
Published: January 2016

Educational innovations are being introduced into medical speciality training. But how do people who participate in medical speciality training (residents, consultants, programme directors) deal with these innovations? And what effects do educational innovations have according to these people?

By addressing these questions, this thesis contributes to the knowledge about the challenging process of innovating medical speciality training.
Transience and multifractal analysis
Authors: Iommi Godofredo , Jordan Thomas , Todd Mike
Published: January 2016

We study dimension theory for dissipative dynamical systems, proving a conditional variational principle for the quotients of Birkhoff averages restricted to the recurrent part of the system. On the other hand, we show that when the whole system is considered (and not just its recurrent part) the conditional variational principle does not necessarily hold. Moreover, we exhibit an example of a topologically transitive map having discontinuous Lyapunov spectrum. The mechanism producing all these pathological features on the multifractal spectra is transience, that is, the non-recurrent part of the dynamics.
Comorbidities Among Women with Vulvovaginal Complaints in Family Practice
Authors: Leusink Peter , Kaptheijns Anne , Laan Ellen , van Boven Kees , Lagro-Janssen Antoine
Published: January 2016

Background

The lifetime prevalence of women suffering from provoked vestibulodynia (PVD) is estimated to be approximately 15%. The etiology of PVD is not yet clear. Recent studies approach PVD as a chronic multifactorial sexual pain disorder. PVD is associated with pain syndromes, genital infections, and mental disorders, which are common diseases in family practice. PVD, however, is not included in the International Classification of Primary Care. Hence, the vulvovaginal symptoms, which could be suggestive of PVD, are likely to be missed.

Aim

To explore the relationship between specific vulvovaginal symptoms that could be suggestive of PVD (genital pain, painful intercourse, other symptoms/complaints related to the vagina/vulva), and related diseases such as pain syndromes, psychological symptom diagnoses, and genital infections in family practice.

Methods

A retrospective analysis of all episodes from 1995 to 2008 in 784 women between 15 and 49 years were used to determine the posterior probability of a selected diagnosis in the presence of specific vulvovaginal symptoms suggestive of PVD expressed in an odds ratio. Selected comorbidities were pain syndromes (muscle pain, general weakness, irritable bowel syndrome [IBS]), psychological symptom diagnoses (anxiety, depression, insomnia), vulvovaginal candidiasis, and sexual and physical abuse.

Results

Women with symptoms suggestive of PVD were 4 to 7 times more likely to be diagnosed with vulvovaginal candidiasis and 2 to 4 times more likely to be diagnosed with IBS. Some symptoms suggestive of PVD were 1 to 3 times more likely to be diagnosed with complaints of muscle pain, general weakness, insomnia, depressive disorder, and feeling anxious.

Conclusion

Data from daily family practice showed a clear relationship between symptoms suggestive of PVD and the diagnoses of vulvovaginal candidiasis and IBS in premenopausal women. Possibly, family doctors make a diagnosis of vulvovaginal candidiasis or IBS based only on clinical manifestations in many women in whom a diagnosis of PVD would be more appropriate.
Sexual Activity, Psychosexual Distress, and Fear of Progression in Women with Human Papillomavirus-Related Premalignant Genital Lesions
Authors: Nagele Eva , Reich Olaf , Greimel Elfriede , Dorfer Martha , Haas Josef , Trutnovsky Gerda
Published: January 2016

Introduction

Genital human papillomavirus (HPV) infections are very common in women 18 to 30 years old and substantially affect women's sexual health.

Aim

To examine sexual activity, psychosexual distress, and fear of progression in women diagnosed with HPV-related precancerous genital lesions.

Methods

In this observational study, women diagnosed with premalignant lesions of the cervix, vagina, or vulva were recruited from a university hospital–based colposcopy clinic.

Main Outcome Measures

Quantitative data from three validated patient-administered questionnaires (Sexual Activity Questionnaire, German version of the Cervical Dysplasia Distress Questionnaire, and Fear of Progression Questionnaire) were compared within the study population, according to the location of the genital lesion, and with relevant reference populations. Qualitative data from two written open-ended questions about women's thoughts regarding diagnosis and information were analyzed.

Results

Two-hundred nine women completed the questionnaires. Seventy-eight percent of women (n = 162) were referred for evaluation of suspect lesions of the cervix, 8% (n = 17) of the vagina, and 14% (n = 30) of the vulva. There were no significant differences in questionnaire results among the three patient groups, except for sexual consequences (Cervical Dysplasia Distress Questionnaire) and recent sexual activity (Sexual Activity Questionnaire). Women with vulvar lesions were most likely to worry about sexual consequences (ie, being unable to have children, being sexually less attractive, or infecting a sexual partner; P = .04). The Sexual Activity Questionnaire subscales sexual pleasure (P = .15) and sexual habits (P = 1.00) were similar to those in a healthy control population, whereas sexual discomfort (P = .51) was comparable to that in a reference population of women who survived cervical cancer. The subscale partner-specific concerns (Fear of Progression Questionnaire) was similar to that in a reference population of patients with cancer (P = .28).

Conclusion

HPV-related precancerous genital lesions, especially of the vulva, are likely to cause concerns about sexual health. Effective information and communication are important to lessen negative sexual consequences and anxiety.
Swallowing Training Combined With Game‐Based Biofeedback in Poststroke Dysphagia
Authors: Li Chih‐Ming , Wang Tyng‐Guey , Lee Hsiao‐Yu , Wang Hsueh‐Pei , Hsieh Shang‐Heng , Chou Michelle , Jason Chen Jia‐Jin
Published: January 2016

Background

For patients with dysphagia due to stroke, in addition to compensatory strategies, exercises are used to help improve motor function. Biofeedback is used in neuromuscular training and is promising for swallowing training.

Objective

To evaluate the functional value of game‐based biofeedback in swallowing therapy for patients with poststroke dysphagia.

Design

A case‐control study.

Setting

Academic tertiary hospital.

Participants

Subjects with poststroke dysphagia (n = 20) were individually matched to 2 separate groups, a game‐based biofeedback group (n = 10) or a control group (n = 10), for age, gender, duration of dysphagia, and dysphagia grades.

Interventions

Each participant underwent 1‐hour sessions 3 times per week for a total of 16 treatment sessions. Each session included a 30‐minute session of traditional swallow treatment and a 30‐minute session of laryngeal elevation exercises. In the experimental group, laryngeal elevation exercises were combined with additional game‐based biofeedback.

Main Outcome Measures

Outcomes assessed before and after interventions included hyoid bone displacement, Functional Oral Intake Scale (FOIS) scores, and nasogastric (NG) tube removal rate.

Results

Intergroup analyses showed larger differences in hyoid bone displacement and FOIS scores (before and after treatment) in the experimental group than in the control group, with statistical significance (P = .007 and P = .014, respectively). Intergroup analyses showed that the hyoid bone displacement change and FOIS scores before and after treatment exhibited statistically significant improvement only in the experimental group (P = .002 and P = .004, respectively). In all, 8 of 10 patients (80%) in the experimental group and 2 of 10 patients (20%) in the control group discontinued NG tube insertion after therapy. Participation in the experimental group was associated with an increased probability of tube removal (odds ratio = 6.00; 95% confidence interval = 1.08‐33.27, P = .009).

Conclusions

Laryngeal elevation training combined with game‐based biofeedback augments the change in hyoid bone displacement and FOIS scores, and increases the NG tube removal rate in patients with poststroke dysphagia.
THE FIRST WORD: TO BE HUMAN IS TO BE FREE
Authors: Tutu Desmond M.
Published: January 2016

In this essay, Archbishop Tutu explains how Christianity understands the inherent freedom, dignity, and human rights of each person to be a consequence of being created in the image of God. This idea contains radical liberative potential to challenge oppression and create structures for human flourishing. While Christianity has not always lived up to the liberative potential of its teachings, and too often has contributed to hatred, oppression, and violence, Archbishop Tutu argues, the power of religious voices remains essential in the struggle against oppression and for the protection of human dignity.
ON NUMBER FIELDS WITHOUT A UNIT PRIMITIVE ELEMENT
Authors: ZAÏMI T. , BERTIN M. J. , ALJOUIEE A. M.
Published: January 2016

We characterise number fields without a unit primitive element, and we exhibit some families of such fields with low degree. Also, we prove that a noncyclotomic totally complex number field $K$, with degree $2d$ where $d$ is odd, and having a unit primitive element, can be generated by a reciprocal integer if and only if $K$ is not CM and the Galois group of the normal closure of $K$ is contained in the hyperoctahedral group $B_{d}$.
LAW, DEMOCRACY, AND CONSTITUTIONALISM: REFLECTIONS ON EVANS v ATTORNEY GENERAL
Authors: Allan T.R.S.
Published: January 2016

The difference of judicial opinion in the Supreme Court in Evans provokes reflection on fundamental constitutional principles, such as parliamentary sovereignty and the rule of law. A statute that on its face seems to permit a government minister to override a judicial decision of which he disapproves inevitably raises acute concern; the correct reading of the statute depends on the most persuasive integration of basic principles, placing the text within its wider constitutional context. The Justices deployed distinctions between law, fact, and public interest in rather different ways, reflecting their divergent interpretative approaches. The role of constitutional convention is also of particular interest – central to the legal issues arising, on one view, but largely irrelevant on another. At the root of these disagreements lie contrasting conceptions of law and adjudication.
Good, Good For, and Good Relative To: Relative and Relational in Value Theory
Authors: Fritzson Fritz-Anton
Published: January 2016

This paper discusses how we are to understand claims to the effect that something is good relative to a person. It is argued that goodness relative to should not be equated with good for as the latter is a relational value notion and the former is a value theoretical notion. It is argued further that good relative to a person should be understood as good from the perspective or the point of view of the person. But this analysis of the notion ‘good relative to’ leaves open questions about the full nature of relative goodness. For that, a positive proposal about what it is for something to be good relative to a person's point of view is needed. One such proposal is put forward on which the relevant perspective is determined or fixed in terms of the pro and con attitudes of the individual person.
The knowledge gap in world politics: Assessing the sources of citizen awareness of the United Nations Security Council
Authors: Dellmuth Lisa Maria
Published: January 2016

The past decades have seen a significant expansion in the scope and authority of international organisations (IOs), raising questions about who participates and is represented in the public contestation of IOs. An important precondition for citizens to become critically involved in the public debate about an IO is that they are aware of the politics of that IO. This article sheds light on this largely unexplored issue, asking why some citizens are more aware of IOs than others. This question is examined in the context of a powerful international organisation, the United Nations Security Council. Using a multilevel analysis of citizens in 17 Asian and European countries, this article argues that citizen knowledge about the Council is shaped by economic conditions and cosmopolitan identity. Higher levels of knowledge are found among the wealthier, and there is some evidence that income inequality depresses knowledge among poorer citizens. Furthermore, citizens identifying with groups or individuals across nation-state borders are more likely to know more about the Council. The article sketches broader implications for the study of the politicisation of IOs and citizen representation in the public contestation of IOs.
Rethinking national temporal orders: the subaltern presence and enactment of the political
Authors: Väyrynen Tarja
Published: January 2016

How the past is remembered is fundamental to the production and reproduction of postwar sovereign political power. However, Internation Relations’ (IR) explicit interest in the practices of remembrance, and particularly in time remains a relatively new one. This article seeks to show how Jacques Rancière’s discussion of temporality, subaltern history, and politics – which allows the study of parallel and enmeshing temporal universes – contributes to the IR literature on time. In this view, when speech is acquired by those whose right to speak is not recognised they can produce temporalities that disturb hegemonic representations of time constellations and reorganise the nation’s relationship to its past. The article analyses the moment of Kaisu Lehtimäki’s telling her war story in public, and understands it to be a material and symbolic event that shatters the hegemonic distribution of the Finnish postwar national history and truth.
AGGREGATING MORAL PREFERENCES
Authors: Adler Matthew D.
Published: January 2016

Preference-aggregation problems arise in various contexts. One such context, little explored by social choice theorists, is metaethical. ‘Ideal-advisor’ accounts, which have played a major role in metaethics, propose that moral facts are constituted by the idealized preferences of a community of advisors. Such accounts give rise to a preference-aggregation problem: namely, aggregating the advisors’ moral preferences. Do we have reason to believe that the advisors, albeit idealized, can still diverge in their rankings of a given set of alternatives? If so, what are the moral facts (in particular, the comparative moral goodness of the alternatives) when the advisors do diverge? These questions are investigated here using the tools of Arrovian social choice theory.
CHANGING FACE OF MEDICARE’S NATIONAL COVERAGE DETERMINATIONS FOR TECHNOLOGY
Authors: Chambers James D. , Chenoweth Matthew D. , Pyo Junhee , Cangelosi Michael J. , Neumann Peter J.
Published: January 2016

Objectives: The Centers for Medicare and Medicaid Services (CMS) issues National Coverage Determinations (NCDs) for medical interventions expected to have a significant impact on Medicare, the health insurance program for US citizens aged 65 years and older and certain people with disabilities under the age of 65 years. The objective of this study was to evaluate NCDs issued from 1999 to 2013 to identify key trends, and to discuss implications for future CMS policy.

Methods: We used the Tufts Medical Center Medicare National Coverage Determination Database to examine characteristics of NCDs from 1999 through 2013. We examined various characteristics of NCDs, including: whether the intervention under review is used for prevention or treatment of disease, the type of intervention considered, evidence limitations cited by CMS, and coverage determination outcome. We evaluated longitudinal trends in categorical and continuous variables in the database, using Cochran-Armitage trend tests and linear regression, respectively.

Results: We found that NCDs increasingly focus on preventive care (p = 0.072), pertain to diagnostic imaging (p = 0.033), and evaluate health education/behavioral therapy interventions (p = 0.051). CMS increasingly cites the lack of relevant outcomes (p = 0.019) and the lack of applicability of study results to the Medicare population (p < 0.001) as evidence limitations. CMS less often restricts coverage to certain population subgroups in NCDs (p < 0.001), but increasingly applies coverage with evidence development policies (p < 0.001).

Conclusions: Identified trends reflect broader changes in Medicare as CMS shifts its focus from treatment to prevention of disease, addresses potentially overutilized technologies, and attempts to issue flexible coverage policies.
Comparative sequence analyses of rhodopsin and RPE65 reveal patterns of selective constraint across hereditary retinal disease mutations
Authors: HAUSER FRANCES E. , SCHOTT RYAN K. , CASTIGLIONE GIANNI M. , VAN NYNATTEN ALEXANDER , KOSYAKOV ALEXANDER , TANG PORTIA L. , GOW DANIEL A. , CHANG BELINDA S.W.
Published: January 2016

Retinitis pigmentosa (RP) comprises several heritable diseases that involve photoreceptor, and ultimately retinal, degeneration. Currently, mutations in over 50 genes have known links to RP. Despite advances in clinical characterization, molecular characterization of RP remains challenging due to the heterogeneous nature of causal genes, mutations, and clinical phenotypes. In this study, we compiled large datasets of two important visual genes associated with RP: rhodopsin, which initiates the phototransduction cascade, and the retinoid isomerase RPE65, which regenerates the visual cycle. We used a comparative evolutionary approach to investigate the relationship between interspecific sequence variation and pathogenic mutations that lead to degenerative retinal disease. Using codon-based likelihood methods, we estimated evolutionary rates (dN/dS) across both genes in a phylogenetic context to investigate differences between pathogenic and nonpathogenic amino acid sites. In both genes, disease-associated sites showed significantly lower evolutionary rates compared to nondisease sites, and were more likely to occur in functionally critical areas of the proteins. The nature of the dataset (e.g., vertebrate or mammalian sequences), as well as selection of pathogenic sites, affected the differences observed between pathogenic and nonpathogenic sites. Our results illustrate that these methods can serve as an intermediate step in understanding protein structure and function in a clinical context, particularly in predicting the relative pathogenicity (i.e., functional impact) of point mutations and their downstream phenotypic effects. Extensions of this approach may also contribute to current methods for predicting the deleterious effects of candidate mutations and to the identification of protein regions under strong constraint where we expect pathogenic mutations to occur.
Mandatory Rest Stops Improve Athlete Safety during Event Medical Coverage for Ultramarathons
Authors: Joslin Jeremy , Mularella Joshua , Bail Allison , Wojcik Susan , Cooney Derek R.
Published: January 2016

Introduction

Provisions of medical direction and clinical services for ultramarathons require specific attention to heat illness. Heat stress can affect athlete performance negatively, and heat accumulation without acclimatization is associated with the development of exertional heat stroke (EHS). In order to potentially mitigate the risk of this safety concern, the Jungle Marathon (Para, Brazil) instituted mandatory rest periods during the first two days of this 7-day, staged, Brazilian ultramarathon.

Methods

Race records were reviewed retrospectively to determine the number of runners that suffered an emergency medical complication related to heat stress and did not finish (DNF) the race. Review of records included three years before and three years after the institution of these mandatory rest periods.

Results

A total of 326 runners competed in the Jungle Marathon during the 2008-2013 period of study. During the pre-intervention years, a total of 46 athletes (21%) DNF the full race with 25 (54.3%) cases attributed to heat-related factors. During the post-intervention years, a total of 26 athletes (24.3%) DNF the full race with four (15.4%) cases attributed to heat-related factors.

Conclusion

Mandatory rest stops during extreme running events in hot or tropical environments, like the Jungle Marathon, are likely to improve athlete safety and improve the heat acclimatization process.

JoslinJ, MularellaJ, BailA, WojcikS, CooneyDR. Mandatory rest stops improve athlete safety during event medical coverage for ultramarathons. Prehosp Disaster Med. 2016;31(1):43–45.
A Course on Terror Medicine: Content and Evaluations
Authors: Cole Leonard A. , Natal Brenda , Fox Adam , Cooper Arthur , Kennedy Cheryl A. , Connell Nancy D. , Sugalski Gregory , Kulkarni Miriam , Feravolo Michael , Lamba Sangeeta
Published: January 2016

Introduction

The development of medical school courses on medical responses for disaster victims has been deemed largely inadequate. To address this gap, a 2-week elective course on Terror Medicine (a field related to Disaster and Emergency Medicine) has been designed for fourth year students at Rutgers New Jersey Medical School in Newark, New Jersey (USA). This elective is part of an overall curricular plan to broaden exposure to topics related to Terror Medicine throughout the undergraduate medical education.

Rationale

A course on Terror Medicine necessarily includes key aspects of Disaster and Emergency Medicine, though the converse is not the case. Courses on Disaster Medicine may not address features distinctively associated with a terror attack. Thus, a terror-related focus not only assures attention to this important subject but to accidental or naturally occurring incidents as well.

Methods

The course, implemented in 2014, uses a variety of teaching modalities including lectures, videos, and tabletop and hands-on simulation exercises. The subject matter includes biological and chemical terrorism, disaster management, mechanisms of injury, and psychiatry. This report outlines the elective’s goals and objectives, describes the course syllabus, and presents outcomes based on student evaluations of the initial iterations of the elective offering.

Results

All students rated the course as “excellent” or “very good.” Evaluations included enthusiastic comments about the content, methods of instruction, and especially the value of the simulation exercises. Students also reported finding the course novel and engaging.

Conclusion

An elective course on Terror Medicine, as described, is shown to be feasible and successful. The student participants found the content relevant to their education and the manner of instruction effective. This course may serve as a model for other medical schools contemplating the expansion or inclusion of Terror Medicine-related topics in their curriculum.

ColeLA, NatalB, FoxA, CooperA, KennedyCA, ConnellND, SugalskiG, KulkarniM, FeravoloM, LambaS. A course on Terror Medicine: content and evaluations. Prehosp Disaster Med. 2016;31(1):98–101.
High Dynamic Range Pixel Array Detector for Scanning Transmission Electron Microscopy
Authors: Tate Mark W. , Purohit Prafull , Chamberlain Darol , Nguyen Kayla X. , Hovden Robert , Chang Celesta S. , Deb Pratiti , Turgut Emrah , Heron John T. , Schlom Darrell G. , Ralph Daniel C. , Fuchs Gregory D. , Shanks Katherine S. , Philipp Hugh T. , Muller David A. , Gruner Sol M.
Published: January 2016

We describe a hybrid pixel array detector (electron microscope pixel array detector, or EMPAD) adapted for use in electron microscope applications, especially as a universal detector for scanning transmission electron microscopy. The 128×128 pixel detector consists of a 500 µm thick silicon diode array bump-bonded pixel-by-pixel to an application-specific integrated circuit. The in-pixel circuitry provides a 1,000,000:1 dynamic range within a single frame, allowing the direct electron beam to be imaged while still maintaining single electron sensitivity. A 1.1 kHz framing rate enables rapid data collection and minimizes sample drift distortions while scanning. By capturing the entire unsaturated diffraction pattern in scanning mode, one can simultaneously capture bright field, dark field, and phase contrast information, as well as being able to analyze the full scattering distribution, allowing true center of mass imaging. The scattering is recorded on an absolute scale, so that information such as local sample thickness can be directly determined. This paper describes the detector architecture, data acquisition system, and preliminary results from experiments with 80–200 keV electron beams.
Differential mortality, aging and social security: delaying the retirement age when educational spillovers matter
Authors: LE GARREC GILLES , LHUISSIER STÉPHANE
Published: January 2016

To lower the forecasted increase in the social security burden linked to population aging, delaying the legal age of retirement has been privileged throughout industrialized countries. Compared with a uniform delay, some argue that those who have entered precociously the labor market should be allowed to retire earlier. They assert that such a ‘long career’ exception is all the more justified that those unskilled workers live also less long due to heavier and potentially health-damaging jobs. In this paper, we then study macroeconomic and distributional consequences of global gain in life expectancy, with or without the postponement of the legal age of retirement and with or without a ‘long career’ exception. By considering a framework where individuals decide to acquire skills depending on economic incentives and differential mortality, we focus particularly on spillover effects possibly generated by education. We show in particular that introducing a ‘long career’ exception cannot be to the advantage of future unskilled workers unless education yields no spillover effects.
The association between the serotonin and dopamine neurotransmitters and personality traits
Authors: Delvecchio G. , Bellani M. , Altamura A. C. , Brambilla P.
Published: January 2016

Evidence from previous studies has reported that complex traits, including psychiatric disorders, are moderately to highly heritable. Moreover, it has also been shown that specific personality traits may increase the risk to develop mental illnesses. Therefore the focus of the research shifted towards the identification of the biological mechanisms underpinning these traits by exploring the effects of a constellation of genetic polymorphisms in healthy subjects. Indeed, studying the effect of genetic variants in normal personality provides a unique means for identifying candidate genes which may increase the risk for psychiatric disorders. In this review, we discuss the impact of two of the most frequently studied genetic polymorphisms on personality in healthy subjects, the 5-HTT polymorphism of the serotonin transporter and the DRD2/DRD4 polymorphisms of the D2/D4 dopamine's receptors. The main aims are: (a) to highlight that the study of candidate genes provides a fruitful ground for the identification of the biological underpinnings of personality without, though, reaching a general consensus about the strength of this relationship; and (b) to outline that the research in personality genetics should be expanded to provide a clearer picture of the heritability of personality traits.
Seasonal variation in major depressive episode prevalence in Canada
Authors: Patten S. B. , Williams J. V. A. , Lavorato D. H. , Bulloch A. G. M. , Fiest K. M. , Wang J. L. , Sajobi T. T.
Published: January 2016

Background.

The purpose of this paper is to describe variation, over the months of the year, in major depressive episode (MDE) prevalence. This is an important aspect of the epidemiological description of MDE, and one that has received surprisingly little attention in the literature. Evidence of seasonal variation in MDE prevalence has been weak and contradictory. Most studies have sought to estimate the prevalence of seasonal affective disorder using cut-points applied to scales assessing mood seasonality rather than MDE. This approach does not align with modern classification in which seasonal depression is a diagnostic subtype of major depression rather than a distinct category. Also, some studies may have lacked power to detect seasonal differences. We addressed these limitations by examining the month-specific occurrence of conventionally defined MDE and by pooling data from large epidemiological surveys to enhance precision in the analysis.

Method.

Data from two national survey programmes (the National Population Health Survey and the Canadian Community Health Survey) were used, providing ten datasets collected between 1996 and 2013, together including over 500,000. These studies assessed MDE using a short form version of the Composite International Diagnostic Interview (CIDI) for major depression, with one exception being a 2012 survey that used a non-abbreviated version of the CIDI. The proportion of episodes occurring in each month was evaluated using items from the diagnostic modules and statistical methods addressing complex design features of these trials. Overall month-specific pooled estimates and associated confidence intervals were estimated using random effects meta-analysis and a gradient was assessed using a meta-regression model that included a quadratic term.

Results.

There was considerable sampling variability when the month-specific proportions were estimated from individual survey datasets. However, across the various datasets, there was sufficient homogeneity to justify the pooling of these estimated proportions, producing large gains in precision. Seasonal variation was clearly evident in the pooled data. The highest proportion of episodes occurred in December, January and February and the lowest proportions occurred in June, July and August. The proportion of respondents reporting MDE in January was 70% higher than August, suggesting an association with implications for health policy. The pattern persisted with stratification for age group, sex and latitude.

Conclusions.

Seasonal effects in MDE may have been obscured by small sample sizes in prior studies. In Canada, MDE has clear seasonal variation, yet this is not addressed in the planning of services. These results suggest that availability of depression treatment should be higher in the winter than the summer months.
Low adherent cancer cell subpopulations are enriched in tumorigenic and metastatic epithelial-to-mesenchymal transition-induced cancer stem-like cells
Authors: Morata-Tarifa Cynthia , Jiménez Gema , García María A. , Entrena José M. , Griñán-Lisón Carmen , Aguilera Margarita , Picon-Ruiz Manuel , Marchal Juan A.
Published: January 2016

Cancer stem cells are responsible for tumor progression, metastasis, therapy resistance and cancer recurrence, doing their identification and isolation of special relevance. Here we show that low adherent breast and colon cancer cells subpopulations have stem-like properties. Our results demonstrate that trypsin-sensitive (TS) breast and colon cancer cells subpopulations show increased ALDH activity, higher ability to exclude Hoechst 33342, enlarged proportion of cells with a cancer stem-like cell phenotype and are enriched in sphere- and colony-forming cells in vitro. Further studies in MDA-MB-231 breast cancer cells reveal that TS subpopulation expresses higher levels of SLUG, SNAIL, VIMENTIN and N-CADHERIN while show a lack of expression of E-CADHERIN and CLAUDIN, being this profile characteristic of the epithelial-to-mesenchymal transition (EMT). The TS subpopulation shows CXCL10, BMI-1 and OCT4 upregulation, differing also in the expression of several miRNAs involved in EMT and/or cell self-renewal such as miR-34a-5p, miR-34c-5p, miR-21-5p, miR-93-5p and miR-100-5p. Furthermore, in vivo studies in immunocompromised mice demonstrate that MDA-MB-231 TS cells form more and bigger xenograft tumors with shorter latency and have higher metastatic potential. In conclusion, this work presents a new, non-aggressive, easy, inexpensive and reproducible methodology to isolate prospectively cancer stem-like cells for subsequent biological and preclinical studies.
LEGO: a novel method for gene set over-representation analysis by incorporating network-based gene weights
Authors: Dong Xinran , Hao Yun , Wang Xiao , Tian Weidong
Published: January 2016

Pathway or gene set over-representation analysis (ORA) has become a routine task in functional genomics studies. However, currently widely used ORA tools employ statistical methods such as Fisher’s exact test that reduce a pathway into a list of genes, ignoring the constitutive functional non-equivalent roles of genes and the complex gene-gene interactions. Here, we develop a novel method named LEGO (functional Link Enrichment of Gene Ontology or gene sets) that takes into consideration these two types of information by incorporating network-based gene weights in ORA analysis. In three benchmarks, LEGO achieves better performance than Fisher and three other network-based methods. To further evaluate LEGO’s usefulness, we compare LEGO with five gene expression-based and three pathway topology-based methods using a benchmark of 34 disease gene expression datasets compiled by a recent publication and show that LEGO is among the top-ranked methods in terms of both sensitivity and prioritization for detecting target KEGG pathways. In addition, we develop a cluster-and-filter approach to reduce the redundancy among the enriched gene sets, making the results more interpretable to biologists. Finally, we apply LEGO to two lists of autism genes and identify relevant gene sets to autism that could not be found by Fisher.
Design of chimeric antigen receptors with integrated controllable transient functions
Authors: Juillerat Alexandre , Marechal Alan , Filhol Jean-Marie , Valton Julien , Duclert Aymeric , Poirot Laurent , Duchateau Philippe
Published: January 2016

The ability to control T cells engineered to permanently express chimeric antigen receptors (CARs) is a key feature to improve safety. Here, we describe the development of a new CAR architecture with an integrated switch-on system that permits to control the CAR T-cell function. This system offers the advantage of a transient CAR T-cell for safety while letting open the possibility of multiple cytotoxicity cycles using a small molecule drug.
Protein Secondary Structure Prediction Using Deep Convolutional Neural Fields
Authors: Wang Sheng , Peng Jian , Ma Jianzhu , Xu Jinbo
Published: January 2016

Protein secondary structure (SS) prediction is important for studying protein structure and function. When only the sequence (profile) information is used as input feature, currently the best predictors can obtain ~80% Q3 accuracy, which has not been improved in the past decade. Here we present DeepCNF (Deep Convolutional Neural Fields) for protein SS prediction. DeepCNF is a Deep Learning extension of Conditional Neural Fields (CNF), which is an integration of Conditional Random Fields (CRF) and shallow neural networks. DeepCNF can model not only complex sequence-structure relationship by a deep hierarchical architecture, but also interdependency between adjacent SS labels, so it is much more powerful than CNF. Experimental results show that DeepCNF can obtain ~84% Q3 accuracy, ~85% SOV score and ~72% Q8 accuracy, respectively, on the CASP and CAMEO test proteins, greatly outperforming currently popular predictors. As a general framework, DeepCNF can be used to predict other protein structure properties such as contact number, disorder regions and solvent accessibility.
Tunable atomic spin-orbit coupling synthesized with a modulating gradient magnetic field
Authors: Luo Xinyu , Wu Lingna , Chen Jiyao , Guan Qing , Gao Kuiyi , Xu Zhi-Fang , You L. , Wang Ruquan
Published: January 2016

We report the observation of synthesized spin-orbit coupling (SOC) for ultracold spin-1 87Rb atoms. Different from earlier experiments where a one dimensional (1D) atomic SOC of pseudo-spin-1/2 is synthesized with Raman laser fields, the scheme we demonstrate employs a gradient magnetic field (GMF) and ground-state atoms, thus is immune to atomic spontaneous emission. The strength of SOC we realize can be tuned by changing the modulation amplitude of the GMF and the effect of the SOC is confirmed through the studies of: 1) the collective dipole oscillation of an atomic condensate in a harmonic trap after the synthesized SOC is abruptly turned on; and 2) the minimum energy state at a finite adiabatically adjusted momentum when SOC strength is slowly ramped up. The condensate coherence is found to remain very good after driven by modulating GMFs. Our scheme presents an alternative means for studying interacting many-body systems with synthesized SOC.
An integrated chinmedomics strategy for discovery of effective constituents from traditional herbal medicine
Authors: Wang Xijun , Zhang Aihua , Zhou Xiaohang , Liu Qi , Nan Yang , Guan Yu , Kong Ling , Han Ying , Sun Hui , Yan Guangli
Published: January 2016

Traditional natural product discovery affords no information about compound structure or pharmacological activities until late in the discovery process and leads to low probabilities of finding compounds with unique biological properties. By integrating serum pharmacochemistry-based screening with high-resolution metabolomics analysis, we have developed a new platform, termed chinmedomics which is capable of directly discovering the bioactive constituents. In this work, the focus is on ShenQiWan (SQW) treatment of ShenYangXu (SYX, kidney-yang deficiency syndrome) as a case study, as determined by chinmedomics. With serum pharmacochemistry, a total of 34 peaks were tentatively characterised in vivo, 24 of which were parent components and 10 metabolites were detected. The metabolic profiling and potential biomarkers of SYX were also investigated and 23 differential metabolites were found. 20 highly correlated components were screened by the plotting of correlation between marker metabolites and serum constituents and considered as the main active components of SQW. These compounds are imported into a database to predict the action targets: 14 importantly potential targets were found and related to aldosterone-regulated sodium reabsorption and adrenergic signaling pathways. Our study showed that integrated chinmedomics is a powerful strategy for discovery and screening of effective constituents from herbal medicines.