bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Lake Wobegon Effect: Are All Cancer Patients above Average?
Authors: WOLF JACQUELINE H. , WOLF KEVIN S. 
Published: December 2013

ContextWhen elderly patients face a terminal illness such as lung cancer, most are unaware that what we term in this article “the Lake Wobegon effect” taints the treatment advice imparted to them by their oncologists. In framing treatment plans, cancer specialists tend to intimate that elderly patients are like the children living in Garrison Keillor's mythical Lake Wobegon: above average and thus likely to exceed expectations. In this article, we use the story of our mother's death from lung cancer to investigate the consequences of elderly people's inability to reconcile the grave reality of their illness with the overly optimistic predictions of their physicians.MethodsIn this narrative analysis, we examine the routine treatment of elderly, terminally ill cancer patients through alternating lenses: the lens of a historian of medicine who also teaches ethics to medical students and the lens of an actuary who is able to assess physicians’ claims for the outcome of medical treatments.FindingsWe recognize that a desire to instill hope in patients shapes physicians’ messages. We argue, however, that the automatic optimism conveyed to elderly, dying patients by cancer specialists prompts those patients to choose treatment that is ineffective and debilitating. Rather than primarily prolong life, treatments most notably diminish patients’ quality of life, weaken the ability of patients and their families to prepare for their deaths, and contribute significantly to the unsustainable costs of the U.S. health care system.ConclusionsThe case described in this article suggests how physicians can better help elderly, terminally ill patients make medical decisions that are less damaging to them and less costly to the health care system.
The effect of Internet distribution on brick‐and‐mortar sales
Authors: Pozzi Andrea 
Published: December 2013

AbstractI examine the introduction of an online shopping service by a large supermarket chain also operating a network of brick‐and‐mortar stores. The establishment of the Internet channel led to a 13 percent increase in overall revenues, with limited cannibalization of traditional sales. I study the mechanisms underlying this result, focusing on two areas. First, I demonstrate the importance of the reduction of customers' travel costs in the attraction of new business. Second, I provide some evidence that revenues increase more in markets where the chain faces more competitors, suggesting that the online channel can help divert business from rival supermarkets.
Congruence test of molecular clock calibration hypotheses based onBayes factor comparisons
Authors: Andújar Carmelo , Soria‐Carrasco Víctor , Serrano José , Gómez‐Zurita Jesús 
Published: December 2013

SummaryMolecular clock calibration is a crucial step for placing phylogenetic trees in the temporal framework required to test evolutionary hypotheses and estimate evolutionary rates. In general, most authors agree that the best approach is to incorporate multiple calibrations to avoid the risk of bias associated with a single dating source. However, the indiscriminate inclusion of as many calibration points as possible can lead to tree shape distortion and an overestimation of the variation in evolutionary rates among branches due to errors in the geological, paleontological or paleogeographic information used for dating.We present a test of congruence among calibration hypotheses to assist their filtering prior to molecular clock analysis, which we have calledBayesFactorClusterAnalysis (BFCA). This is a heuristic method based on the comparison of pairwise calibrations hypotheses byBayes factors that allows identifying sets of congruent calibrations.We have testedBFCAthrough simulation usingbeastandmcmctree programs and analysed a real case of multiple calibration hypotheses to date the evolution of the genusCarabus(Coleoptera:Carabidae).The analyses of simulated data showed the predictability of change inBayes factors when comparing alternative calibration hypotheses on a particular tree topology, and thus the suitability ofBFCAin identifying unreliable calibrations, especially in cases with limited variation in evolutionary rates among branches. The exclusion of inconsistent calibrations as identified byBFCAproduced significant changes in the estimation of divergence times and evolutionary rates in the genusCarabus, illustrating the importance of filtering calibrations before analyses.The method has been implemented in an open‐sourceRpackage calledbfcato simplify its application.
Aging is associated with increased regulatory T‐cell function
Authors: Garg Sanjay K. , Delaney Colin , Toubai Tomomi , Ghosh Amiya , Reddy Pavan , Banerjee Ruma , Yung Raymond 
Published: December 2013

SummaryRegulatory T‐cell (Treg, CD4+CD25+) dysfunction is suspected to play a key role in immune senescence and contributes to increased susceptibility to diseases with age by suppressing T‐cell responses. FoxP3 is a master regulator of Treg function, and its expression is under control of several epigenetically labile promoters and enhancers. Demethylation of CpG sites within these regions is associated with increased FoxP3 expression and development of a suppressive phenotype. We examined differences in FoxP3 expression between young (3–4 months) and aged (18–20 months) C57BL/6 mice. DNA from CD4+ T cells is hypomethylated in aged mice, which also exhibit increased Treg numbers and FoxP3 expression. Additionally, Treg from aged mice also have greater ability to suppress effector T‐cell (Teff) proliferation in vitro than Tregs from young mice. Tregs from aged mice exhibit greater redox remodeling–mediated suppression of Teff proliferation during coculture with DCs by decreasing extracellular cysteine availability to a greater extent than Tregs from young mice, creating an adverse environment for Teff proliferation. Tregs from aged mice produce higher IL‐10 levels and suppress CD86 expression on DCs more strongly than Tregs from young mice, suggesting decreased T‐cell activity. Taken together, these results reveal a potential mechanism of higher Treg‐mediated activity that may contribute to increased immune suppression with age.
Genetic association between NOD2 polymorphism and infection status by Mycobacterium avium ssp. paratuberculosis in German Holstein cattle
Authors: Küpper J. D. , Brandt H. R. , Erhardt G. 
Published: December 2013

SummaryThe aim of the study was the analysis of the nucleotide‐binding oligomerization domain containing 2 (NOD2, formerly CARD15) as a candidate gene for Mycobacterium avium ssp. paratuberculosis infection in cattle. Eleven SNPs in the NOD2 gene were identified, and finally, four SNPs were included in a case–control study using 324 German Holstein cows tested for paratuberculosis using fecal culture and ELISA. The SNP (GenBank) AY518738S04:g.521G>A in exon 4 showed a significant association between the fecal culture status of the animals and NOD2 allele variants. The other three SNPs showed no associations in German Holstein cows.
P‐Wave Abnormality Predicts Recurrence of Atrial Fibrillation after Electrical Cardioversion: A Prospective Study
Authors: Gonna Hanney , Gallagher Mark Michael , Guo Xiao Hua , Yap Yee Guan , Hnatkova Katerina , Camm A. John 
Published: December 2013

BackgroundMaintenance of atrial fibrillation (AF) is related to atrial electrical inhomogeneity and resultant chaotic reentry. Our aim was to test the hypothesis that abnormalities of P morphology on the surface electrocardiogram (ECG) predict recurrent AF following electrical cardioversion (ECV).MethodsA 12‐lead ECG was recorded after ECV for persistent AF in 77 patients (51 men, 65 ± 10 years) and repeated 1 month later. P‐wave duration was obtained in each lead using blinded on‐screen measurement. Maximum P‐wave duration (P‐max) was defined as the longest measurable P‐wave duration in any lead. P‐wave dispersion (PWd) was calculated as the maximum–minimum P‐wave duration.ResultsOne month after ECV, 29 (38%) patients maintained sinus rhythm. Compared with the sinus rhythm group, those with recurrent AF had significantly greater PWd (66 ± 19 vs 57 ± 16 ms, P = 0.024) and included more patients with P‐max ≥142 ms (65% vs 38%, P = 0.023). Using a cutoff of ≥62 ms for PWd and ≥142 ms for P‐max, both indices had similar predictive value (sensitivity 66.7 and 64.6%, specificity 58.6 and 62.1%, respectively). In multiple regression analysis, including established clinical predictors, P‐max ≥142 ms was the only independent predictor of AF recurrence (P = 0.025).ConclusionA prolonged P‐wave duration measured by 12‐lead ECG predicts recurrent AF within 1 month after ECV.
Fatigue effects on the electromechanical delay components during the relaxation phase after isometric contraction
Authors: Cè E. , Rampichini S. , Limonta E. , Esposito F. 
Published: December 2013

AbstractAimBy a combined electromyographic (EMG), mechanomyographic (MMG) and force (F) analysis, the electromechanical delay during muscle relaxation (R‐DelayTOT) was partitioned into electrochemical and mechanical components. The study aimed to evaluate the effects of fatigue on R‐DelayTOT components and to assess their intersession and interday reliability Intraclass correlation coefficient (ICC).MethodsDuring tetanic stimulations, EMG, MMG and F were recorded from the human gastrocnemius medialis muscle before and after fatigue. The latency between EMG and MMG ripple cessations (R‐Δt EMG‐MMGR, electrochemical R‐DelayTOT component); between MMG ripple cessation and F decay onset (R‐Δt MMGR‐F, first R‐DelayTOT mechanical component); and between F decay onset and maximum MMG negative peak (R‐Δt F‐MMGp‐p, second R‐DelayTOT mechanical component) was calculated.ResultsBefore fatigue, R‐Δt F‐MMGp‐p was the major contributor (61.9 ± 1.7 ms, 75%) to R‐DelayTOT (82.7 ± 1.0 ms), while R‐Δt EMG‐MMGR and R‐Δt MMGR‐F accounted for 16% (13.3 ± 1.2 ms) and 9% (7.5 ± 1.0 ms) respectively. After fatigue, R‐DelayTOT, R‐Δt EMG‐MMGR and R‐Δt MMGR‐F increased by 11, 41 and 67%, respectively (P < 0.05), whereas R‐Δt F‐MMGp‐p did not change. Consequently, the relative contribution of R‐Δt EMG‐MMGR, R‐Δt MMGR‐F and R‐Δt F‐MMGp‐p, to R‐DelayTOT changed to 20 ± 2, 12 ± 1 and 68 ± 2% respectively. Measurement reliability was always from high to very high (ICC 0.705–0.959).ConclusionFatigue altered the processes between neuromuscular activation cessation and force decay onset, but not the second mechanical component (cross‐bridges detachment rate and series elastic components release). This combined approach provided reliable measurement of the different R‐DelayTOT components and it may represent a valid tool to get more insights on muscle electromechanical behaviour.
Acting to Let Someone Die
Authors: McGee Andrew 
Published: December 2013

AbstractThis paper examines the recent prominent view in medical ethics that withdrawing life‐sustaining treatment (LST) is an act of killing. I trace this view to the rejection of the traditional claim that withdrawing LST is an omission rather than an act. Although that traditional claim is not as problematic as this recent prominent view suggests, my main claim is that even if we accepted that withdrawing LST should be classified as an act rather than as an omission, it could still be classified as letting die rather than killing. Even though omissions are contrasted with acts, letting die need not be, for one can let die by means of acts. The remainder of the paper is devoted to establishing this claim and addresses certain objections to it.
Design and usability assessment of a dialogue‐based cognitive tutoring system to model expert problem solving in research design
Authors: Hung Wei‐Chen , Smith Thomas J. , Smith M Cecil 
Published: December 2013

AbstractTechnology provides the means to create useful learning and practice environments for learners. Well‐designed cognitive tutor systems, for example, can provide appropriate learning environments that feature cognitive supports (ie, scaffolding) for students to increase their procedural knowledge. The purpose of this study was to conduct a series of usability tests of a dialogue‐based design framework for the presentation of domain knowledge and assess how it can be used to actively engage learners in learning about research methods. Three formal usability assessments and an instructor adoption assessment were conducted during the development of the tutoring system. Each usability assessment employed diverse data collection methods to ensure broad and in‐depth coverage of findings. The findings revealed that the dialogue metaphor enabled natural and participatory interactions between the system and users. The feedback prompts or hints and support resources provided opportunities for learning during the process of problem solving. Future research to extend the support of usability assessments is also discussed.
Clinical and Neuropathological Variability in Clinically Isolated Central Nervous System Whipple's Disease
Authors: Balasa Mircea , Gelpi Ellen , Rey MJ , Vila Jordi , Ramió‐Torrentà Lluís , Quiles Granado Ana Ma , Molina Latorre Ricard , Lepidi Hubert , Raoult Didier , Saiz Albert 
Published: December 2013

AbstractCentral nervous system Whipple's disease (CNS‐WD) with clinically isolated neurological involvement is a rare condition fatal without an early diagnosis. We aimed to present clinical and neuropathological features of three cases of pre‐ or post‐mortem polymerase chain reaction confirmed CNS‐WD with distinct clinical presentation, outcome and pathological findings. One patient had an acute onset with spinal and brainstem involvement and died without CNS‐WD diagnosis after 14 weeks. Neuropathology showed extensive inflammatory and necrotizing lesions with abundant foamy periodic‐acid‐Schiff (PAS)+ macrophages. The second patient had a subacute evolution with late CNS‐WD diagnosis and death occurring 18 months after onset despite antibiotic treatment. Brain examination showed inflammatory lesions in the brainstem, thalamus and cerebellum, and abundant foamy PAS+ macrophages. The third case was diagnosed within 4 weeks of onset and treated with an excellent response. He died after a disease‐free period of 24 months of unrelated causes. Neuropathology showed cystic residual lesions devoid of microorganisms without inflammatory reaction. CNS‐WD may have an acute or subacute course with variable response to treatment. Accordingly, subjacent lesions may be those of a severe acute necrotizing encephalitic process or subacute inflammatory lesions involving diencephalic, brainstem, cerebellar and spinal regions. Chronic, cavitary brain lesions may be sequelae of a successful treatment. Early diagnosis should allow appropriate treatment and improve prognosis.
Change practice now! Using atraumatic needles to prevent post lumbar puncture headache
Authors: Davis A. , Dobson R. , Kaninia S. , Espasandin M. , Berg A. , Giovannoni G. , Schmierer K. 
Published: December 2013

Background and purposeLumbar puncture (LP) is a key diagnostic procedure in medicine. Post lumbar puncture headache (PLPHA) is a well recognized complication of LP. Evidence suggests that using atraumatic needles for diagnostic LP (ATNLP) reduces risk of PLPHA. However, clinicians in Europe and the USA routinely use traumatic needles for diagnostic LP (TNLP). The occurrence of PLPHA following ATNLP and TNLP was compared in a clinical setting. Further, a survey was performed exploring use of ATNLP amongst UK neurologists.MethodsService development study. Patients were followed up 2 and 7 days after LP using blinded telephone assessment. A questionnaire was developed to assess use of ATNLP amongst UK neurologists. Frequency, onset, duration and severity of PLPHA were recorded as were use of analgesia, general practitioner consultations, hospital readmissions, days off work due to PLPHA and cost. Neurologists were asked about their familiarity with, and use of, ATNLP.ResultsOne hundred and nine participants attending the Royal London Hospital were included, and 74 attendees of the Association of British Neurologists 2012 conference completed an on‐site questionnaire. ATNLP reduced the rate of PLPHA (27.1% vs. 60.4%; P < 0.01). In those participants who developed PLPHA symptoms were short lived (mean 50 h vs. 94 h, P = 0.02) and less severe after ATNLP. Use of ATNLP led to significant cost savings. Only one in five UK neurologists regularly use ATNLP stating lack of training and availability of atraumatic needles as main reasons.ConclusionsATNLP significantly reduces the risk of PLPHA. Training is required 3 to facilitate a change from TNLP to ATNLP amongst clinicians.
Evaluation of the sedative, analgesic, clinicophysiological and haematological effects of intravenous detomidine, detomidine‐butorphanol, romifidine and romifidine‐butorphanol in standing donkeys
Authors: El‐Kammar M. H. , Gad S. B. 
Published: December 2013

SummaryThe aim of this investigation was to determine and evaluate the sedative, analgesic, clinicophysiological and haematological effects of intravenous (i.v.) injection of detomidine, detomidine‐butorphanol, romifidine and romifidine‐butorphanol. Six standing donkeys were used. Each donkey received 4 i.v. treatments and the order of treatment was randomised with a one‐week interval between each treatment. We found that i.v. injection of a combination of detomidine‐butorphanol or romifidine‐butorphanol produced potent neuroleptanalgesic effects thus providing better, safe and effective sedation with complete analgesia in standing donkeys compared with injection of detomidine or romifidine alone. The changes and reduction in pulse rate were within acceptable limits. The changes in clinicophysiological, haematological and biochemical values were mild and transient in these clinically healthy donkeys.
Regulation of α–endosulfine, an inhibitor of protein phosphatase 2A, by multisite phosphorylation
Authors: Mochida Satoru 
Published: December 2013

Progression into M phase requires inhibition of heterotrimeric PP2A containing the regulatory B55 subunit (PP2A–B55) as well as the activation of cyclin‐dependent kinase 1 (Cdk1). α–endosulfine (ENSA)/cyclic AMP‐regulated 19 kDa phosphoprotein (ARPP–19) family proteins phosphorylated at S67 by Greatwall kinase bind and inhibit PP2A–B55. This study shows that endogenous kinases phosphorylate not only S67 but also two additional sites in ENSA (T28 and S109) with different kinetics at different cell‐cycle stages in Xenopus laevis intact cells and cell‐free egg extracts. When assayed in vitro, these phosphorylations had qualitatively and/or quantitatively different effects on inhibition of PP2A–B55 by ENSA. Structural analyses revealed that the most‐conserved middle region of ENSA containing S67 physically interacts with PP2A–B55 at the interface of the B55 and C subunits, where the catalytic centre of PP2A is located. As non‐phosphorylated ENSA has an intrinsic potential for PP2A–B55 inhibition, these three phosphorylations differentially affect physical interaction of the middle region of ENSA with PP2A–B55. These results suggest that the two additional phosphorylation sites together with S67 allow ENSA to function as a ‘stepwise tuner’ for PP2A–B55, which may be regulated by multiple cellular signals, rather than a simple ‘on/off’ switch.
Environmental drivers of macroinvertebrate communities in high Arctic rivers (Svalbard)
Authors: Blaen Phillip J. , Brown Lee E. , Hannah David M. , Milner Alexander M. 
Published: December 2013

Summary

The impacts of climate‐induced environmental changes on freshwater biodiversity are not well understood in Arctic regions.
We quantified water source contributions (meltwater, ground water), environmental habitat conditions and benthic macroinvertebrate community dynamics in north‐west Svalbard. The aim was to use contemporary findings to infer how future environmental change may affect these Arctic river ecosystems.
Water source dynamics played an important role in influencing environmental habitat conditions; meltwater contributions to flow were related significantly to discharge, channel stability, electrical conductivity and pH.
Low regional benthic macroinvertebrate diversity relative to other Arctic regions was attributed to harsh winter conditions and biogeographical dispersal constraints associated with the Svalbard archipelago.
Generalised estimating equations and multivariate ordination models showed benthic macroinvertebrate diversity and abundance were influenced significantly by several environmental habitat variables. Rivers in non‐glacierised basins typically supported more diverse and abundant communities than those in glacierised basins, most likely as a consequence of the warmer water temperature and less‐disturbed habitat conditions associated with these systems.
Consequently, shifts in water source contributions driven by changes in climate may alter environmental habitat conditions in Svalbard rivers and could lead to an increase in abundance and diversity among some freshwater macroinvertebrate communities.
Habitat heterogeneity influences the response of microbial communities to severe low‐flow periods in alluvial wetlands
Authors: Foulquier Arnaud , Dehedin Arnaud , Piscart Christophe , Montuelle Bernard , Marmonier Pierre 
Published: December 2013

Summary

Microbial communities play a central role in the functioning of freshwater ecosystems, but the impact of severe low flow on microbial processes at the floodplain scale is largely unexplored, especially in terms of patterns in decline of water level. The differential responses of benthic and interstitial microbial communities are also unknown.

We explored the structural and functional responses of bacterial and fungal communities to severe low‐flow periods at the surface and deep in the sediment of three types of wetland, namely running water, upwelling zones and isolated pools.

The different wetland types exhibited distinct microbial communities but the low‐flow period induced homogenisation of community composition among wetland types. Despite a convergence in microbial community composition, the response of microbial processes differed among wetland types during the low‐flow period: a decrease in biomass and activity in running water and upwelling sites contrasted with an increase observed in isolated pools.

Microbial communities and processes deep in the sediment appeared less affected by the low‐flow period and wetland type, but were not insensitive. Homogenisation of community compositions at 50 cm depth was observed 1 month after the low‐flow period, suggesting drivers distinct from those at the surface. Our results demonstrate the predominant effect of environmental conditions on rates of microbial processes as opposed to community composition.

Wetland heterogeneity, in terms of modalities of water level decrease, seems to be important for the maintenance of microbial processes at the floodplain scale in the context of increasing frequency and severity of low‐flow periods.
Distinguishing autotrophic and heterotrophic respiration based on diel oxygen change curves: revisiting Dr. Faustus
Authors: Kosten Sarian , Demars Benoît O. L. , Moss Brian 
Published: December 2013

Summary

In his paper ‘Climate change, nutrient pollution and the bargain of Dr. Faustus’, Moss (Freshwater Biology, 55, 2010, 175) described the interacting and mutually reinforcing effects of climate change and nutrient pollution on aquatic ecosystems.

Among other things, Moss (Freshwater Biology, 55, 2010, 175) proposed a simple method for determining autotrophic and heterotrophic respiration rates (Ra and Rh) based on the diel oxygen change technique. Here, we show that one of the assumptions on which the method is based is flawed and that Ra and Rh cannot be derived mathematically from diel oxygen change curves.