bluuebunny/crossref_metadata_2025 huggingface dataset:
Archiving, ordering, and searching: search engines, algorithms, databases, and deep mediatization
Authors: Andersen Jack
Published: February 2018

This article argues that search engines, algorithms, and databases can be considered as a way of understanding deep mediatization. They are embedded in a variety of social and cultural practices, and as such, they change our communicative actions to be shaped by their logic of archiving, ordering, and searching. I argue that, increasingly and in particular ways, search engines, algorithms, and databases shape our everyday communicative actions as they make us think, internalize, and act along the lines of their particular modes of communication action. After having briefly reviewed recent trends in mediatization research, the argument is discussed and unfolded in between the material and social constructivist-phenomenological interpretations of mediatization. In conclusion, it is discussed how deep this form of mediatization can be taken to be.
Mothers and Fathers Matter: The Influence of Parental Support, Hostility, and Problem Solving on Adolescent Friendships
Authors: Flynn Heather Kohler , Felmlee Diane H. , Shu Xiaoling , Conger Rand D.
Published: February 2018

We examine the pathways by which parents influence adolescents’ close friendships, focusing on three types of behavioral styles: hostile, warm, and problem solving. Structural equation models are estimated using data at two time points from the Iowa Youth and Families Project ( N = 227 friendship pairs). Results suggest that the lives of adolescents and both their mother and father are inexorably linked. Observed interactions with a close friend at Time 2 reveal teens recreate their parents’ original hostile, supportive, and problem-solving styles from Time 1. This outcome depends on (a) type of behavior and (b) gender. Mothers’ supportive behavior, fathers’ problem solving, and both parents’ hostile behavior significantly influence adolescents’ comparable interaction styles. Adolescents’ subsequent behavior toward their friend significantly affects friendship quality. Lower levels of hostile behavior in female youth, increased problem solving by males, and supportive actions toward a friend for both relate positively to rewarding friendships.
Information needs and barriers of rural smallholder farmers in developing countries
Authors: Phiri Austine , Chipeta George T , Chawinga Winner D
Published: February 2018

The purpose of the study was to investigate the information needs and barriers of rural smallholder farmers in Mzimba North in Malawi. A mixed methods approach was adopted for the study and the Wilson’s Model of Information Behaviour (1996) guided the study. A questionnaire and focus group discussion guide were used to collect data from 202 rural smallholder farmers. The study found that the major information need of rural smallholder farmers was crop husbandry as revealed by the majority of rural smallholder farmers 149 (77.6). The study found that majority of rural smallholder farmers 180 (94.8%) were aware of information sources. The study also found that the predominant information sources consulted by rural smallholder farmers were personal experiences as indicated by the majority of rural smallholder farmers 185 (96%). The major challenge faced by rural smallholder farmers was lack of mobility as revealed by the majority of rural smallholder farmers 147 (76.6). The study recommends that the Department of Agriculture Extension Services (DAES) should empower the social structures such as families in rural settings with agricultural information.
Family Firm Brands, Perceptions of Doing Good, and Consumer Happiness
Authors: Schellong Margarete , Kraiczy Nils D. , Malär Lucia , Hack Andreas
Published: February 2018

This research examines how and why family firm brands (compared to nonfamily firm brands) affect consumers. We argue that a brand’s family firm status acts as a signal to consumers who share category-based beliefs about family firms doing good due to preserving their socioemotional wealth. This perception in turn is a fair and positive appraisal in the mind of consumers (in the sense of indirectly benefiting others with their spent financial resources) that elicits happiness. In an experimental study, we show that family firms are being perceived by consumers as acting more supportive towards internal and external stakeholders and that these perceptions in turn result in higher consumer happiness. In other words, our results indicate that communicating a brand’s family firm status might have a positive indirect influence on consumer happiness through the perception of doing good. On the other hand, our results suspect that a brand's family firm status might also trigger beliefs (not part of our study) with more negative indirect effects on consumer happiness.
On the vibration analysis of off-road vehicles: Influence of terrain deformation and irregularity
Authors: Reina Giulio , Leanza Antonio , Messina Arcangelo
Published: February 2018

Surface irregularity acts as a major excitation source in off-road driving that induces vibration of the vehicle body through the tire assembly and the suspension system. When adding ground deformability, this excitation is modulated by the soil properties and operating conditions. The underlying mechanisms that govern ground behavior can be explained and modeled drawing on Terramechanics. Based on this theory, a comprehensive quarter-car model of off-road vehicle is presented that takes into account tire/soil interaction. The model can handle the general case of compliant wheel rolling on compliant ground and it allows ride and road holding performance to be evaluated in the time and frequency domain.

An extensive set of simulation tests is included to assess the impact of various surface roughness and ground deformability through a parameter study, showing the potential of the proposed model to describe the behavior of off-road vehicles for design and performance optimization purposes.
Successful use of cytarabine and bendamustine in a patient with mantle cell lymphoma and acute renal failure using intermittent hemodialysis: A case report
Authors: Ettleson Matthew , Bongers Kale S , Vitale Kaitlyn , Perissinotti Anthony J. , Phillips Tycel , Marini Bernard L.
Published: February 2018

Mantle cell lymphoma is a mature B-cell non-Hodgkin lymphoma characterized by the hallmark (11;14) chromosomal translocation, which often presents with lymphadenopathy and extra-nodal involvement. Young, fit patients are generally treated with chemotherapy approaches that incorporate high-dose cytarabine (e.g. the Nordic regimen) followed by autologous hematopoietic cell transplantation. Because of the significant activity of cytarabine in mantle cell lymphoma, increasingly, high- and intermediate-dose cytarabine are being used in the treatment of elderly mantle cell lymphoma patients. In practice, many patients present with significant organ dysfunction and there is limited data on the use of high- to intermediate-dose cytarabine and bendamustine in this setting. Here, we report a case of a critically ill, elderly patient with mantle cell lymphoma and concomitant acute kidney injury and oliguria who was successfully treated with a cycle of cytarabine (Ara-C) and bendamustine accompanied by intermittent hemodialysis.
Does Severity Explain Differences in Hospital Length of Stay for Pneumonia Patients?
Authors: Iezzoni Lisa I. , Shwartz Michael , Ash Arlene S. , Mackiernan Yevgenia D.
Published: February 2018

Objectives:

In the USA, the role of patient severity in determining hospital resource use has been questioned since Medicare adopted prospective hospital payment based on diagnosis-related groups (DRGs). Exactly how to measure severity, however, remains unclear. We examined whether assessments of severity-adjusted hospital lengths of stay (LOS) varied when different measures were used for severity adjustment

Methods:

The complete study sample included 18 016 patients receiving medical treatment for pneumonia at 105 acute care hospitals. We studied 11 severity measures, nine based on patient demographic and diagnosis and procedure code information and two derived from clinical findings from the medical record. For each severity measure, LOS was regressed on patient age, sex, DRG, and severity score. Analyses were performed on trimmed and untrimmed data. Trimming eliminated cases with LOS more than three standard deviations from the mean on a log scale.

Results:

The trimmed data set contained 17 976 admissions with a mean (S.D.) LOS of 8.9 (6.1) days. Average LOS ranged from 5.0–11.8 days among the 105 hospitals. Using trimmed data, the 11 severity measures produced Rsquared values ranging from 0.098–0.169 for explaining LOS for individual patients. Across all severity measures, predicted average hospital LOS varied much less than the observed LOS, with predicted mean hospital LOS ranging from about 8.4–9.8 days.

Discussion:

No severity measure explained the two-fold differences among hospitals in average LOS. Other patient characteristics, practice patterns, or institutional factors may cause the wide differences across hospitals in LOS.
Using Economics to Prioritize Research: A Case Study of Randomized Trials for the Prevention of Hip Fractures Due to Osteoporosis
Authors: Torgerson David , Donaldson Cam , Reid David
Published: February 2018

Objectives:

To assess the role of economics, in combination with clinical judgement, for setting research priorities, using osteoporosis prevention (and, as a result, hip fracture prevention) as an example.

Methods:

Modelling the cost and effectiveness of each of six potential interventions to prevent hip fractures over the 5-year length of a randomized trial (vitamin D injection; thiazide diuretics; hormone replacement therapy; oral calcium and vitamin D; calcium alone; calcitonin). Drug costs were derived from the Monthly Index of Medical Specialties (MIMS); averted fracture costs and estimates of effectiveness were derived from published sources.

Results:

Vitamin D injection proved to be the most potentially cost-effective treatment with a cost-effectiveness ratio of £584. If averted costs are included, this leads to a saving of £9 176 496 per 100 000 women treated. By contrast, the most expensive therapy was calcitonin (marginal cost-effectiveness ratio of £433 548). This suggests that priority should be given to trials assessing the effectiveness of vitamin D injections.

Conclusions:

Relatively simple economic modelling exercises can inform research priorities and could help optimize the use of scarce research resources.
Costs and Remuneration for Cervical Screening in General Practice in the West of Scotland
Authors: Myles Susan , Wyke Sally , Ibbotson Tracy , Macintyre Sally , McEwen Jim , Kelly Moya
Published: February 2018

Objectives:

To investigate associations between costs and remuneration for cervical screening in general practice in relation to skill mix, features of practice structure and deprivation levels in the local area; and, to identify efficient policies for organising cervical screening in general practice.

Method:

Questionnaire survey and interview study in 87 general practices in Greater Glasgow Health Board an area in the west of Scotland which covers a socio-economically varied population. The main outcome measures were remuneration to cost ratios (RCRs) for cervical screening and their natural logarithms (logRCRs).

Results:

Both the costs of cervical screening and RCRs varied widely between the 87 practices taking part. RCRs ranged from 0.29 to 14.67 (mean 2.64, median 2.18, interquartile range 1.15–2.98). Twenty-one per cent (18) of practices earned less than they spent on the organisation of screening, whilst 9% (8) of practices had RCRs of more than 5:1. RCRs were significantly lower if medical staff were involved in either taking smears or dealing with results. RCRs did not vary by social deprivation score, despite uptake being lower in practices in more deprived areas. This was explained by nurses working in practices in deprived areas being more likely to take smears than nurses working in more affluent areas. Sensitivity analyses were undertaken, altering key time and cost assumptions. As a result, the absolute values of the RCRs changed, although the overall pattern of association did not, with the exception of doctor involvement in processing results which was no longer significant when average general practitioners’ income was substituted for locum rates.

Conclusions:

Practices in deprived areas may be responding to greater pressure of work by making optimal use of skill mix within the primary health care team. A more graduated incentive payment scheme may more fairly reward practices in deprived areas which are less likely to achieve 80% uptake due to relatively intractable features of practice structure. Assuming that practice nurses provide an equivalent quality of service to that provided by general practitioners, results suggest that doctor-nurse substitution would be cost-effective for general practice based cervical screening. Resource savings (principally doctor's time) could be redeployed to other areas of primary health care.
Development and Testing of the UK SF-12
Authors: Jenkinson Crispin , Layte Richard
Published: February 2018

Objectives:

The 36 item short form health survey (SF-36) has proved to be of use in a variety of settings where a short generic health measure of patient-assessed outcome is required. This measure can provide an eight dimension profile of health status, and two summary scores assessing physical function and mental well-being. The developers of the SF-36 in America have developed algorithms to yield the two summary component scores in a questionnaire containing only one-third of the original 36 items, the SF-12. This paper documents the construction of the UK SF-12 summary measures from a large-scale dataset from the UK in which the SF-36, together with other questions on health and lifestyles, was sent to randomly selected members of the population. Using these data we attempt here to replicate the findings of the SF-36 developers in the UK setting, and then to assess the use of SF-12 summary scores in a variety of clinical conditions.

Methods:

Factor analytical methods were used to derive the weights used to construct the physical and mental component scales from the SF-36. Regression methods were used to weight the 12 items recommended by the developers to construct the SF-12 physical and mental component scores. This analysis was undertaken on a large community sample ( n = 9332), and then the results of the SF-36 and SF-12 were compared across diverse patient groups (Parkinson's disease, congestive heart failure, sleep apnoea, benign prostatic hypertrophy).

Results:

Factor analysis of the SF-36 produced a two factor solution. The factor loadings were used to weight the physical component summary score (PCS-36) and mental component summary score (MCS-36). Results gained from the use of these measures were compared with results gained from the PCS-12 and MCS-12, and were found to be highly correlated (PCS: ρ = 0.94, p < 0.001; MCS: ρ = 0.96, p < 0.001), and produce remarkably similar results, both in the community sample and across a variety of patient groups.

Conclusions:

The SF-12 is able to produce the two summary scales originally developed from the SF-36 with considerable accuracy and yet with far less respondent burden. Consequently, the SF-12 may be an instrument of choice where a short generic measure providing summary information on physical and mental health status is required. Crispin Jenkinson DPhil, Deputy Director
Unequal Randomisation Can Improve the Economic Efficiency of Clinical Trials
Authors: Torgerson David , Campbell Marion
Published: February 2018

Objectives:

In the majority of clinical trials patients are randomised equally between treatment groups. This approach maximises statistical power for a given total sample size. The objectives of this paper were to determine if, when research costs between treatments differ, it is more economically efficient to randomise additional patients to the cheaper treatment, and how the optimum randomisation ratio can be estimated.

Methods:

Estimation of the most economically efficient randomisation ratio for four hypothetical clinical trials using cost-effectiveness analysis.

Results:

When research costs differ between treatments, and there is no constraint on total sample size, it is always more cost-effective to randomise more patients to the cheaper treatment. For example, a cost ratio between the lesser and more expensive treatment of ten, results in a randomisation ratio of 3.2:1.

Conclusions:

Unequal randomisation ratios should be more widely used as this will achieve optimum statistical power for the lowest expenditure of research resources.
Reluctant Rationers: Public Input to Health Care Priorities
Authors: Lomas Jonathan
Published: February 2018

Members of the public can adopt any one of at least three roles when providing input to public decision-making: Taxpayer, collective community decision-maker, or patient. Each of these potential roles can be mapped onto three areas of public policy decision-making in health care: Funding levels and organization for the system, the services we choose to offer under public funding, and the characteristics of those who should receive the offered services.

The increasing desire to involve the public across the spectrum of health care decision-making has yet to result in a clear delineation of either which of the areas are most appropriate for public input or which of the roles we wish individual participants to adopt. The average citizen (as opposed to the self-interested patient, the provider or the manager) has so far shown little interest in contributing and rarely has the requisite skills for most of the tasks asked of him or her.

The widespread motivation of governments and others for seeking public input appears to be to get the public to take or share ownership in the tough rationing choices consequent on fiscal retrenchment in health care. Evaluation of existing literature leads to the conclusion that there are only limited areas where we might wish to obtain significant public input if we adopt this widespread policy motivation. Specifically, the general public should be asked to give input to, but not determine, priorities across the broad service categories that could potentially be publicly funded. Members of the public have neither the interest nor the skills to do this at the level of specific services. The role expected of such members of the public should be made explicit and should focus on collective views of the community good rather than self-interested views of individual benefit.

Groups of patients, however, should be the source of input when socio-demographic characteristics are being used to decide who should receive offered services. The role expected of these consumers is not, however, to take a self-interested perspective; rather, it is to adopt Rawls' veil of ignorance' to reflect compassionate views of priorities across socio-demographic characteristics.

Finally, there appears to be no best method for obtaining public input that overcomes the common problems of poor information upon which to base priorities, difficulty in arriving at consensus, poor representativeness of participants, and lack of opportunity for informed discussion prior to declaring priorities. There is some suggestion, however, that panels of citizens or patients, convened on an ongoing basis and provided with the opportunity to acquire relevant information and discuss its implications prior to making consensus recommendations, offer the most promising way forward.
Partnerships with Patients: The Pros and Cons of Shared Clinical Decision-Making
Authors: Coulter Angela
Published: February 2018

The traditional style of medical decision-making in which doctors take sole responsibility for treatment decisions is being challenged. Attempts are being made to promote shared decision-making in which patients are given the opportunity to express their values and preferences and to participate in decisions about their care. Critics of shared decision-making argue that most patients do not want to participate in decisions; that revealing the uncertainties inherent in medical care could be harmful; that it is not feasible to provide information about the potential risks and benefits of all treatment options; and that increasing patient involvement in decision-making will lead to greater demand for unnecessary, costly or harmful procedures which could undermine the equitable allocation of health care resources. This article examines the evidence for and against these claims. There is considerable evidence that patients want more information and greater involvement, although knowledge about the circumstances in which shared decision-making should be encouraged, and the effects of doing so, is sparse. There is an urgent need for more research into patients' information needs and preferences and for the development and evaluation of decision-support mechanisms to enable patients to become informed participants in treatment decisions.
Strategies for the Management of Hypercholesterolaemia: A Systematic Review of the Cost-Effectiveness Literature
Authors: Morris Stephen , McGuire Alistair , Caro Jaime , Pettitt Daniel
Published: February 2018

Objective:

To review research addressing the management of cholesterol in the prevention of coronary heart disease in order to assess the cost-effectiveness of such interventions.

Methods:

A systematic review of economic evaluations identified through searches of MEDLINE and the Social Sciences Citation Index revealed 38 studies addressing the cost-effectiveness of cholesterol management. They were distinguished according to screening approaches, dietary advice and drug treatment. Most studies were not associated directly with clinical trial results, but adopted economic modelling approaches.

Results:

Whilst there is general agreement among the majority of analyses, studies of cholesterol management concerned with screening strategies were extremely sensitive to changes in their assumptions; so much so that only a limited emphasis may be placed on specific cost-effectiveness ratios and the conclusions drawn from them. All studies considered direct costs, though many were limited to drug costs. The cost-effectiveness of primary prevention by cholesterol-lowering drugs is highly variable, depending on age at initiation of treatment and cardiovascular risk profile. Pharmacological intervention is least cost-effective in the young and the elderly. The cost-effectiveness of cholesterol-reducing agents improves when they are targeted at those at high risk. HMG-CoA reductase inhibitors are generally more effective and more cost-effective at reducing cholesterol-related coronary events than other medications.

Conclusion:

The methods and economic data upon which these studies are based need to be improved if robust policy conclusions are to be formulated.
Newcomers in a Global Industry: Challenges of a Norwegian Game Company
Authors: Jørgensen Kristine
Published: February 2018

This article presents results from a study of work practices in a Norwegian game development studio. Identifying key challenges faced by the company, the article argues that the combination of project management issues and a lack of human and financial resources led the company into an unfortunate situation where they were simultaneously working on two overlapping projects and thus were forced to cancel one of the projects. Further, the article also discusses how welfare measures related to cultural policy support system and work environment legislation may have impacted upon the process.
Friends With Benefits: Plausible Optimism and the Practice of Teabagging in Video Games
Authors: Myers Brian
Published: February 2018

Recent scholarship in gaming studies has challenged the field to investigate and critique the hard core gaming audience (stereotypically seen as straight, White, cis-gendered male gamers) in a way that does not reinforce either the perceived marginalization of gamers or broader social hierarchies of gender, sexuality, and class. This article demonstrates a way to acknowledge the complexity of this audience without dismissing its most virulent tendencies via practice theory and weak theory. Using data drawn from a qualitative survey of 393 self-identified first-person shooter video game players, this article looks at the specific practice of “teabagging” in online competitive gaming contexts. Ultimately, this article argues that drawing attention to the gaps and fissures that local gaming practices can produce in broader structures of gaming, sexuality, and class can help critical gaming scholars encourage and cultivate such practices as well as construct new, reparative alliances between different fields and communities.
Computer Game Fan Communities, Community Management, and Structures of Membership
Authors: Zimmerman Joshua J.
Published: February 2018

Community management is an important but relatively understudied facet of computer game development. This article begins filling this gap by examining how community managers in the computer game industry manage communities of players through the establishment of structures of membership: positions and practices designed to encourage membership hierarchies. Beginning with the construction of an analytical framework through which to understand different subcommunity activities, this article then examines structures of membership at every stage of Kim’s membership life cycle and, ultimately, how those structures help to attract, educate, and retain dedicated community members.
Neighborhood Contexts and Marijuana Use Among Urban Dwelling Emerging Adult Men
Authors: Taggart Tamara , Brown Andre L. , Kershaw Trace
Published: February 2018

Neighborhoods are key socio-environmental contexts for marijuana use during emerging adulthood. This study examined the relationships between neighborhood context, traditional masculine norms (status, toughness, and anti-femininity), and marijuana use among 119 majority African American emerging adult men in a small urban community. Poisson regression models were used to determine the associations between neighborhood problems, social cohesion, and marijuana use. Moderator effects were examined to determine if masculinities modified these associations. Neighborhood problems and social cohesion were positively associated with marijuana use. Men who had a lower endorsement of some traditional masculine norms had greater marijuana use compared to men with a higher endorsement of these norms. These findings have implications for intervention strategies and policies.
Understanding the Impact of Fibromyalgia on Men: Findings From a Nationwide Survey
Authors: Muraleetharan Daenuka , Fadich Ana , Stephenson Colin , Garney Whitney
Published: February 2018

Fibromyalgia (FM) is a serious condition that affects approximately four million people in the United States, and is underdiagnosed in men. The objective of this study was to understand this phenomenon by examining multiple impacts of fibromyalgia on men in regard to interactions in society and the U.S. health system. A qualitative survey was administered to 1,163 respondents both online and in-person in Tennessee, Virginia, Maryland, and Washington, DC. Thematic analyses of the survey responses suggest that men with FM have negative experiences with (1) physical and mental health, (2) quality of life, (3) relationships, and (4) careers as a result of FM. Interactions with health-care providers were deterred by (1) potential for misdiagnosis or dismissal of symptoms, (2) stigma of having a condition primarily affecting women, (3) differences in treatment of men and women with FM, and (4) need for health education resources. These findings dictate a need to improve communication between health-care providers and male FM patients.
Antimicrobial Pharmacotherapy Management of Urinary Tract Infections in Pediatric Patients
Authors: Lashkar Manar O. , Nahata Milap C.
Published: February 2018

Objective: To discuss the risk factors, microbial resistance rates, and pharmacotherapy, including antimicrobial choices and medication dosage regimens, for urinary tract infections (UTIs) in pediatric patients. Data Sources: A MEDLINE literature search (1985 to December 2017) was performed using the following keywords and associated medical subject headings: urinary tract infection, antimicrobial, treatment, and children. Study Selection and Data Extraction: Search was conducted to identify clinical trials, systematic reviews, and guidelines. Search was filtered to include studies with age range between birth and 18 years and published in English. Additional references were identified from selected review articles. Data Synthesis: In total, 27 studies investigating microbial resistance, 31 studies assessing antimicrobial efficacy, 34 studies describing prophylaxis, and 6 systematic reviews were included. The resistance patterns differed across age groups and affected the choice of empirical therapy. If pyelonephritis is suspected, empiric antimicrobials should have high urinary and sufficient parenchymal concentrations. Nitrofurantoin has low microbial resistance rates and can generally be used empirically for treating uncomplicated cystitis in children >1 month of age. Trimethoprim-sulfamethoxazole resistance has increased and should be avoided unless local susceptibility data are available. Certain patients with recurrent UTIs or renal abnormalities may require antimicrobial prophylaxis, which may be associated with adverse effects, such as intolerability or an increased risk of microbial resistance. Conclusion: The resistance pattern of uropathogens should be considered prior to initiating therapy. Controlled trials with large samples are needed to compare the treatment duration of various antimicrobial regimens and the specific role of prophylactic antimicrobials.
Prognostic value of baseline metabolic tumor volume in early-stage Hodgkin lymphoma in the standard arm of the H10 trial
Authors: Cottereau Anne-Ségolène , Versari Annibale , Loft Annika , Casasnovas Olivier , Bellei Monica , Ricci Romain , Bardet Stéphane , Castagnoli Antonio , Brice Pauline , Raemaekers John , Deau Bénédicte , Fortpied Catherine , Raveloarivahy Tiana , Van Zele Emelie , Chartier Loic , Vander Borght Thierry , Federico Massimo , Hutchings Martin , Ricardi Umberto , Andre Marc , Meignan Michel
Published: February 2018

Key Points

Baseline metabolic tumor volume is a strong prognostic factor in early-stage HL. Baseline metabolic tumor volume affects the early response to treatment and, combined with early PET, improves risk stratification.
B-cell targeting in chronic graft-versus-host disease
Authors: Zeiser Robert , Sarantopoulos Stefanie , Blazar Bruce R.
Published: February 2018

Over the last decade, our understanding of the pathophysiology of chronic graft-versus-host disease (cGVHD) has improved considerably. In this spotlight, we discuss emerging insights into the pathophysiology of cGVHD with a focus on B cells. First, we summarize supporting evidence derived from mouse and human studies. Next, novel cGVHD therapy approaches that target B cells will be covered to provide treating physicians with an overview of the rationale behind the emerging armamentarium against cGVHD.
Improving T-cell expansion and function for adoptive T-cell therapy using ex vivo treatment with PI3Kδ inhibitors and VIP antagonists
Authors: Petersen Christopher T. , Hassan Mojibade , Morris Anna B. , Jeffery Jasmin , Lee Kunhee , Jagirdar Neera , Staton Ashley D. , Raikar Sunil S. , Spencer Harold T. , Sulchek Todd , Flowers Christopher R. , Waller Edmund K.
Published: February 2018

Key Points

Number of prior chemotherapy cycles in cancer patients correlates with T-cell senescent phenotype and loss of CD27 and CD28 expression. Addition of PI3Kδ inhibitors and VIP antagonists increased ex vivo expansion, in vivo persistence, and anticancer cytotoxicity of T cells.
First trimester fetal size and prescribed asthma medication at 15 years of age
Authors: Turner Steve , Fielding Shona , Devereux Graham
Published: February 2018

There is increasing evidence that antenatal factors predispose to childhood asthma. We tested the hypothesis that reduced first trimester fetal size is associated with increased risk for asthma at 15 years of age.

Fetal size in the first and second trimester was ascertained by ultrasound scan. The primary outcome of being dispensed one or more asthma medications by the family doctor in the year before the 15th birthday was determined from routinely acquired dispensing data.

Dispensing data were available for 1699 (88% of the original cohort) participants at 15 years of age and questionnaire data for 750 (39%). Each reduction in z-score for first trimester size was associated with increased odds for dispensed asthma medication at 15 years of age (OR 1.26, 95% CI 1.03–1.54) and self-reported use of asthma medications (OR 1.55, 95% CI 1.16–2.08). Overall, first and second trimester size and forced expiratory volume in 1 s at ages 5, 10 and 15 years were reduced for those dispensed asthma medications compared with those not dispensed asthma medications (p=0.003).

Antenatal factors that are active by the first trimester may contribute to respiratory well-being throughout childhood. Dropout from a birth cohort study can overestimate of the magnitude of any true association.
Efficacy of web-based cognitive–behavioural therapy for chronic fatigue syndrome: randomised controlled trial
Authors: Janse A. , Worm-Smeitink M. , Bleijenberg G. , Donders R. , Knoop H.
Published: February 2018

Background

Face-to-face cognitive–behavioural therapy (CBT) leads to a reduction of fatigue in chronic fatigue syndrome (CFS).

Aims

To test the efficacy of internet-based CBT (iCBT) for adults with CFS.

Method

A total of 240 patients with CFS were randomised to either iCBT with protocol-driven therapist feedback or with therapist feedback on demand, or a waiting list. Primary outcome was fatigue severity assessed with the Checklist Individual Strength (Netherlands Trial Register: NTR4013).

Results

Compared with a waiting list, intention-to-treat (ITT) analysis showed a significant reduction of fatigue for both iCBT conditions (protocol-driven feedback: B = −8.3, 97.5% CI −12.7 to −3.9, P < 0.0001; feedback on demand: B = −7.2, 97.5% CI −11.3 to –3.1, P < 0.0001). No significant differences were found between both iCBT conditions on all outcome measures (P = 0.3–0.9). An exploratory analysis revealed that feedback-on-demand iCBT required less therapist time (mean 4 h 37 min) than iCBT with protocol-driven feedback (mean 6 h 9 min, P < 0.001) and also less than face-to-face CBT as reported in the literature.

Conclusions

Both iCBT conditions are efficacious and time efficient.

Declaration of interest

None.
Dysregulation of Kupffer Cells/Macrophages and Natural Killer T Cells in Steatohepatitis in LXRα Knockout Male Mice
Authors: Endo-Umeda Kaori , Nakashima Hiroyuki , Umeda Naoki , Seki Shuhji , Makishima Makoto
Published: February 2018

Liver X receptor (LXR) α expression is mainly localized to metabolic tissues, such as the liver, whereas LXRβ is ubiquitously expressed. LXRα is activated by oxysterols and plays an important role in the regulation of lipid metabolism in metabolic tissues. In macrophages, LXRs stimulate reverse cholesterol transport and regulate immune responses. Although a high-cholesterol diet induces severe steatohepatitis in LXRα-knockout (KO) mice, the underlying mechanisms linking lipid metabolism and immune responses remain largely unknown. In this study, we investigated the role of LXRα in the pathogenesis of steatohepatitis by assessing the effects of a high-fat and high-cholesterol diet (HFCD) on hepatic immune cell proportion and function as well as lipid metabolism in wild-type (WT) and LXRα-KO mice. HFCD feeding induced severe steatohepatitis in LXRα-KO mice compared with WT mice. These mice had higher cholesterol levels in the plasma and the liver and dysregulated expression of LXR target and proinflammatory genes in both whole liver samples and isolated hepatic mononuclear cells. Flow cytometry showed an increase in CD68+CD11b+ Kupffer cells/macrophages and a decrease in invariant natural killer T cells in the liver of HFCD-fed LXRα-KO mice. These mice were more susceptible to lipopolysaccharide-induced liver injury and resistant to inflammatory responses against α-galactosylceramide or concanavalin-A treatment. The findings provide evidence for activation of bone marrow–derived Kupffer cells/macrophages and dysfunction of invariant natural killer T cells in LXRα-KO mouse liver. These findings indicate that LXRα regulates hepatic immune function along with lipid metabolism and protects against the pathogenesis of nonalcoholic steatohepatitis.
Postnatal Changes in Testicular Position Are Associated With IGF-I and Function of Sertoli and Leydig Cells
Authors: Koskenniemi Jaakko J , Virtanen Helena E , Wohlfahrt-Veje Christine , Löyttyniemi Eliisa , Skakkebaek Niels E , Juul Anders , Andersson Anna-Maria , Main Katharina M , Toppari Jorma
Published: February 2018

Context

Despite clinical guidelines calling for repetitive examination of testicular position during childhood, little is known of normal changes in testicular position during childhood, let alone factors that control it.

Objective

To assess changes in and factors associated with testicular position during childhood.

Design

Testicular position (the distance from the pubic bone to the upper pole of the testes) at birth, 3 months, 18 months, 36 months, and 7 years and reproductive hormones at 3 months were measured.

Setting

Prenatally recruited, prospective longitudinal birth cohort.

Participants

A total of 2545 boys were recruited prenatally in a Danish-Finnish birth cohort and had a testicular position examination available. A subset of 680 Danish and 362 Finnish boys had serum reproductive hormone concentrations and insulin-like growth factor I (IGF-I) determined at 3 months.

Main Outcome Measures

Testicular distance to pubic bone (TDP), serum reproductive hormone, and IGF-I concentrations.

Results

TDP increased from birth to 3 months and decreased thereafter. Length, gestational age, weight for gestational age, and penile length were positively associated with larger TDP and thus lower testicular position in a linear mixed-effect model. Furthermore, IGF-I concentration, inhibin B/follicle-stimulating hormone ratio, and testosterone/luteinizing hormone ratio were all independently and positively associated with longer TDP.

Conclusions

We provide longitudinal data on postnatal changes in TDP. TDP is dynamic and associated with Leydig and Sertoli cell function as well as with IGF-I levels during the first months of life at mini-puberty of infancy. TDP may thus be a useful biomarker of postnatal testicular function.
In the Literature Lab
Authors: Pask Kevin
Published: February 2018

The most striking development in literary scholarship since the millennium is the increasing exploration of scientific models for literary research. This reflects an anxiety about the authority of humanistic research that has historical roots, some of them well described in the work of the social anthropologist Ernest Gellner. The “two cultures” debate of the early 1960s, centrally animated by C. P. Snow and F. R. Leavis, made the anxiety of the literary professoriat a matter of public debate that still inflects literary scholarship and theory. The rhetorical amplification of scientism, privileging scientific methodologies or partnership with scientific methodologies, in recent literary-critical scholarship is one result. The older formation of “humanities computing,” for example, has reemerged as the digital humanities, with claims to the status of interpretive methodology, particularly in the work of Franco Moretti. Such claims, however, are sometimes the repackaging of older methodologies.
In vivo imaging of emerging endocrine cells reveals a requirement for PI3K-regulated motility in pancreatic islet morphogenesis
Authors: Freudenblum Julia , Iglesias José A. , Hermann Martin , Walsen Tanja , Wilfinger Armin , Meyer Dirk , Kimmel Robin A.
Published: February 2018

The three-dimensional architecture of the pancreatic islet is critical for beta cell function, but the process of islet formation remains poorly understood due to the difficulties of imaging internal organs with cellular resolution. Within transparent zebrafish larvae, the developing pancreas is relatively superficial and thus amenable to live imaging approaches. We performed in vivo time lapse and longitudinal imaging studies to follow islet develoment, visualizing both naturally occuring islet cells and cells arising with an accelerated time course following an induction approach. These studies revealed previously unappreciated fine dynamic protrusions projecting between neighboring and distant endocrine cells. Using pharmacologic compound and toxin interference approaches, and single-cell analysis of morphology and cell dynamics, we determined that endocrine cell motility is regulated by PI3K and G-protein coupled receptor (GPCR) signaling. Linking cell dynamics to islet formation, perturbation of protrusion formation disrupted endocrine cell coalescence, and correlated with decreased islet cell differentiation. These studies identified novel cell behaviors contributing to islet morphogenesis, and suggest a model in which dynamic, exploratory filopodia establish cell-cell contacts which subsequently promote cell clustering.
Molecular barcoding of viral vectors enables mapping and optimization of mRNAtrans-splicing
Authors: Davidsson Marcus , Díaz-Fernández Paula , Torroba Marcos , Schwich Oliver D. , Aldrin-Kirk Patrick , Quintino Luis , Heuer Andreas , Wang Gang , Lundberg Cecilia , Björklund Tomas
Published: February 2018

Genome editing has proven to be highly potent in the generation of functional gene knockouts in dividing cells. In the CNS however, efficient technologies to repair sequences are yet to materialize. Reprogramming on the mRNA level is an attractive alternative as it provides means to perform in situ editing of coding sequences without nuclease dependency. Furthermore, de novo sequences can be inserted without the requirement of homologous recombination. Such reprogramming would enable efficient editing in quiescent cells (e.g., neurons) with an attractive safety profile for translational therapies. In this study, we applied a novel molecular-barcoded screening assay to investigate RNAtrans-splicing in mammalian neurons. Through three alternative screening systems in cell culture and in vivo, we demonstrate that factors determiningtrans-splicing are reproducible regardless of the screening system. With this screening, we have located the most permissivetrans-splicing sequences targeting an intron in the Synapsin I gene. Using viral vectors, we were able to splice full-length fluorophores into the mRNA while retaining very low off-target expression. Furthermore, this approach also showed evidence of functionality in the mouse striatum. However, in its current form, thetrans-splicing events are stochastic and the overall activity lower than would be required for therapies targeting loss-of-function mutations. Nevertheless, the herein described barcode-based screening assay provides a unique possibility to screen and map large libraries in single animals or cell assays with very high precision.
Οξύς υποφλοιοεπινεφριδισμος (αδισσώνια κρίση) στο σκύλο: αναφορά σε έξι περιστατικά
Authors: KASABALIS (Δ. ΚΑΣΑΜΠΑΛΗΣ) D. , SOUBASIS (Ν. ΣΟΥΜΠΑΣΗΣ) N. , PARDALI (Δ. ΠΑΡΔΑΛΗ) D. , SAVAS (Ι. ΣΑΒΒΑΣ) I. , PAVLIDOU (Κ. ΠΑΥΛΙΔΟΥ) K. , PETANIDES (Θ.Α. ΠΕΤΑΝΙΔΗΣ) T. Α. , PAPADIMITRIOU (Δ. ΠΑΠΑΔΗΜΗΤΡΙΟΥ) D. , VARLAMI (Β. ΒΑΡΛΑΜΗ) V. , KOUTINAS (Α. ΚΟΥΤΙΝΑΣ) A.
Published: February 2018

Medical records of six dogs admitted with acute hypoadrenocorticism were reviewed. All 6 animals were bradycardic and had prolonged capillary refilling time. Hypothermia was detected in 5/6 animals. Clinicopathological evaluation on admission revealed anemia (3/6 dogs), increased (2/6) and normal (2/6) lymphocyte and eosinophil counts, azotemia and hyperkalemia (6/6), hyponatremia, in 5/6 dogs in which sodium was measured with a sodium (Na) : potassium (K) ratio lower than 24, hypoglycemia (2/6) and hypercalcemia, hypocholosterolemia, increased serum alkaline phosphatase and alaninoaminotransferase activities, one dog each. Urine specific gravity was lower than 1025 in 4 dogs. Thoracic radiographs and abdominal ultrasonography disclosed microcardia (2/6), pleural effusion (2/6) and ascites (1/6). Two dogs (2/6), also, presented atrial standstill or atrioventricular block, detected on electrocardiograms. In all 6 animals emergency treatment included the use of intravenous normal saline and glucocorticoids (dexamethasone) immediately after the completion of an ACTH stimulation test with tetracosactide. Two dogs died, one during the 1st day and the other on the 4th day of hospitalization, the latter after the sudden appearance of severe hemorrhagic gastroenteritis. Hospitalization time in the remaining 4 dogs ranged from 3 to 10 days. Prolongation of hospitalization was associated with worsening of anemia, hypoalbuminemia, neurologic complications and non-responsive azotemia. Four dogs (4/6) were discharged on oral prednisolone and fluodrocortisone, but one died after a week for unknown reasons. Acute hypoadrenocorticism is a life threatening condition requiring emergency treatment for a successful outcome. Its inclusion in the differential diagnosis of canine emergencies, presented with acute weakness and gastrointestinal signs, is mandatory, but for its confirmation a complete laboratory and, most importantly, an ACTH stimulation test are always required.
Aujeszky's Disease (Pseudorabies). An old threat in current pig industry? Part I. Pathogenetic information and implications
Authors: PAPAGEORGIOU (Κ.Β. ΠΑΠΑΓΕΩΡΓΙΟΥ) K. V. , BURRIEL A. R. , FILIOUSSIS (Γ. ΦΙΛΙΟΥΣΗΣ) G. , PSYCHAS (Β. ΨΥΧΑΣ) V. , NAUWYNCK H. , KRITAS (Σ.Κ. ΚΡΗΤΑΣ) S.
Published: February 2018

Aujeszky's disease (AD) (or Pseudorabies) is an important viral disease of swine causing neurological signs in neonatal pigs, respiratory problems in fatteners and reproductive disorders in breeding stock. Glycoproteins and enzymes of the AD virus (ADV) and their interactions with the cellular components majorly determine its pathogenesis. After primary replication in the epithelia of the upper respiratory tract, ADV travels via the nerves to the central nervous system and via the blood to secondary replication sites (lymph nodes, lungs, uterus etc). Depending on the age of the affected swine, it can cause neonatal mortality due to neurological disease, respiratory disease in growing and adult pigs and reproductive disorders in breeding animals. One of the characteristic features of ADV is latency. In this paper, its major points on etiology, pathogenesis, clinical and post mortem findings and diagnosis are presented.
Feed Ban and BSE: the detection and identification of processed animal proteins in compound feeds
Authors: ZOIOPOULOS (Π. ΖΩΙΟΠΟΥΛΟΣ) P.
Published: February 2018

Reference is made initially to the incidence of BSE within the EU territory and the reasons of the appearance of the disease i.e. the use of meat and bone meal in ruminant diets. In turn, the evolution of Community legislation in the sector of marketing of feeds of animal origin is described. Furthermore, the banning of feeding of mammalian protein to ruminants and the extension of prohibition to further animal proteins such as from other vertebrates and how this banning affects the feeding of the various animal species is reviewed. Finally, the importance of detecting and identifying the presence and amount of processed animal proteins in compound feed as well as feed materials is stressed and methods such as feed microscopy, immunoassay techniques, PCR, NIR and HPLC are discussed.