bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Inflammation in Acute Intracerebral Hemorrhage with PK11195 PET and Dynamic Contrast‐Enhanced MRI
Authors: Abid Kamran A. , Sobowale Oluwaseun A. , Parkes Laura M. , Naish Josephine , Parker Geoff J.M. , du Plessis Daniel , Brough David , Barrington Jack , Allan Stuart M. , Hinz Rainer , Parry‐Jones Adrian R.
Published: October 2017

BACKGROUND AND PURPOSE

Studies in animal models suggest that inflammation is a major contributor to secondary injury after intracerebral hemorrhage (ICH). Direct, noninvasive monitoring of inflammation in the human brain after ICH will facilitate early‐phase development of anti‐inflammatory treatments. We sought to investigate the feasibility of multimodality brain imaging in subacute ICH.

METHODS

Acute ICH patients were recruited to undergo multiparametric MRI (including dynamic contrast‐enhanced measurement of blood‐brain barrier transfer constant (Ktrans) and PET with [11C]‐(R)‐PK11195). [11C]‐(R)‐PK11195 binds to the translocator protein 18 kDa (TSPO), which is rapidly upregulated in activated microglia. Circulating inflammatory markers were measured at the time of PET.

RESULTS

Five patients were recruited to this feasibility study with imaging between 5 and 16 days after onset. Etiologies included hypertension‐related small vessel disease, cerebral amyloid angiopathy (CAA), cavernoma, and arteriovenous malformation (AVM). [11C]‐(R)‐PK11195 binding was low in all hematomas and 2 (patient 2 [probable CAA] and 4 [AVM]) cases showed widespread increase in binding in the perihematomal region versus contralateral. All had increased Ktrans in the perihematomal region (mean difference = 2.2 × 10−3 minute−1; SD = 1.6 × 10−3 minute−1) versus contralateral. Two cases (patients 1 [cavernoma] and 4 [AVM]) had delayed surgery (3 and 12 months post‐onset, respectively) with biopsies showing intense microglial activation in perilesional tissue.

CONCLUSIONS

Our study demonstrates for the first time the feasibility of performing complex multimodality brain imaging for noninvasive monitoring of neuroinflammation for this severe stroke subtype.
Validating Nonlinear Registration to Improve Subtraction Images for Lesion Detection and Quantification in Multiple Sclerosis
Authors: Kotari Vikas , Salha Racha , Wang Dana , Wood Emily , Salvetti Marco , Ristori Giovanni , Tang Larry , Bagnato Francesca , Ikonomidou Vasiliki N.
Published: October 2017

BACKGROUND AND PURPOSE

To propose and validate nonlinear registration techniques for generating subtraction images because of their ability to reduce artifacts and improve lesion detection and lesion volume quantification.

METHODS

Postcontrast T1‐weighted spin echo and T2‐weighted dual echo images were acquired for 20 patients with relapsing‐remitting multiple sclerosis (RRMS) on a monthly basis for a year (14 women, average age 33.6 ± 6.9). The T2‐weighted images from the first scan were used as a baseline for each patient. The images from the last scan were registered to the baseline image. Four different registration algorithms used for evaluation included; linear, halfway linear, nonlinear, and nonlinear halfway. Subtraction images were generated after brain extraction, intensity normalization, and Gaussian blurring. Lesion activity changes along with identified artifacts were scored on all four techniques by two independent observers. Additionally, quantitative analysis of the algorithms was performed by estimating the volume changes of simulated lesions and real lesions. For real lesion volume change analysis, five subjects were selected randomly. Subtraction images were generated between all the 11 time points and the baseline image using linear and nonlinear registration for the five subjects.

RESULTS

Lesion activity detection resulted in similar performance among the four registration techniques. Lesion volume measurements on subtraction images using nonlinear registration were closer to lesion volume on T2‐weighted images. A statistically significant difference was observed among the four registration techniques while evaluating yin‐yang artifacts. Pairwise comparisons showed that nonlinear registration results in the least amount of yin‐yang artifacts, which are significantly different.

CONCLUSIONS

Nonlinear registration for generation of subtraction images has been demonstrated to be a promising new technique as it shows improvement in lesion activity change detection. This approach decreases the number of artifacts in subtraction images. With improved lesion volume estimates and reduced artifacts, nonlinear registration may lead to discarding less subject data and an improvement in the statistical power of subtraction imaging studies.
Family Influence and R&D Spending in Dutch Manufacturing SMEs: The Role of Identity and Socioemotional Decision Considerations
Authors: Brinkerink Jasper , Bammens Yannick
Published: October 2017

Prior research has revealed a negative association between family influence and R&D spending. The dominant explanation for this association centers on the role of socioemotional considerations in decision‐making. These socioemotional decision considerations are argued to play a more prominent role among family firms and to lower their R&D spending intensity. However, to date, this negative explanatory mechanism has not been empirically verified. Moreover, a deeper analysis of the literature suggests that some family‐induced socioemotional considerations may actually stimulate R&D investments. In this study, four socioemotional decision considerations are delineated—namely, concern for current control, for extended preservation, for organizational reputation, and for organizational values and traditions—of which the first two are anchored in a family's nurturer role identity and the latter two in a family's organizational identification. It is hypothesized that those socioemotional considerations derived from a family's nurturer role identity constrain R&D spending, while those derived from the family's organizational identification boost R&D spending. The empirical study concentrates on the setting of privately held manufacturing SMEs, and using survey data on 365 such companies in the Netherlands, a structural equation model is estimated. The analyses reveal several interesting results: (1) the overall association between family firm status and R&D spending indeed turns out to be negative, and this negative effect is fully explained by family firms' preoccupation with extended preservation; (2) concerns for organizational reputation and for organizational values and traditions partly compensate the negative effect of the extended preservation mechanism. Key academic and practical implications of these findings are discussed.
Highway driving safety the day after using sleep medication: the direction of lapses and excursions out‐of‐lane in drowsy drivers
Authors: Verster Joris C. , Mooren Loes , Bervoets Adriana C. , Roth Thomas
Published: October 2017

The primary outcome measure of the on‐road driving test is the Standard Deviation of Lateral Position. However, other outcome measures, such as lapses and excursions out‐of‐lane, also need to be considered as they may be related to crash risk. The aim of this study was to determine the direction of lapses and excursions out‐of‐lane (i.e. towards/into the adjacent traffic lane or towards/into the road shoulder). In total, data from 240 driving tests were re‐analysed, and 628 lapses and 401 excursions out‐of‐lane were identified. The analyses revealed that lapses were made equally frequently over left (49.4%) and over right (43.3%). In contrast, excursions out‐of‐lane were almost exclusively directed over right into the (safer) road shoulder (97.3%). These findings suggest that drivers are unaware of having lapses, whereas excursions out‐of‐lane are events where the driver is aware of loss of vehicle control.
Environment and dispersal influence changes in species composition at different scales in woody plants of the Western Ghats, India
Authors: Page Navendu V. , Shanker Kartik
Published: October 2017

Question

What are the relative roles of environmental and spatial factors in influencing variation in species composition of tropical woody plants at different spatial scales?

Location

Tropical evergreen forests, Western Ghats, South India.

Methods

Using a plot‐based species inventory spanning the entire latitudinal extent (1,200 km) of the Western Ghats’ wet evergreen forests, we collected primary data on spatial variation in species composition of woody plants. Each plot was characterized by a set of environmental descriptors consisting of topographic, edaphic and climatic variables, while eigenvector‐based spatial variables and plot coordinates were used as spatial descriptors. We used ordination‐based as well as distance‐based variation partitioning techniques to partition the variation in species composition into components uniquely and jointly explained by environmental and spatial factors.

Results

The compositional similarity of woody plants largely showed a linear decline with log‐geographic distance. However, this relationship was spatially structured. After controlling for the differences in environment, compositional similarity was found to be strongly associated with geographic distance only at the smallest spatial scale. Variation partitioning analysis revealed that environmental variables explained a much larger proportion of variation in species composition overall compared to spatial variables. Among environmental variables, climatic variables emerged as the most important predictors of variation in species composition at regional and landscape scales.

Conclusions

Strong association between compositional similarity and geographic distance at local scales indicates the influence of dispersal limitation, while niche differentiation seems to be a more important driver of variation in species composition at larger spatial scales. Overall, our results provide evidence for scale‐dependent shifts in the relative importance of factors that are responsible for variation in species composition.
Empirical Approaches to Measuring the Intelligibility of Different Varieties of English in Predicting Listener Comprehension
Authors: Kang Okim , Thomson Ron I. , Moran Meghan
Published: October 2017

This study compared five research‐based intelligibility measures as they were applied to six varieties of English. The objective was to determine which approach to measuring intelligibility would be most reliable for predicting listener comprehension, as measured through a listening comprehension test similar to the Test of English as a Foreign Language. The speakers included 18 English users representing six distinct varieties. These speakers’ speech was evaluated by 60 listeners, users of the same English varieties who completed the listening comprehension test as well as five intelligibility tasks, all recorded by the speakers. The five measures of intelligibility included responses to true/false statements, scalar ratings of speech, perception of nonsense sentences, perception of filtered sentences, and transcription of speech; these measures were compared in terms of their relationship to listening comprehension scores using linear mixed‐effects models. Results showed that the measure of intelligibility based on listeners’ responses to nonsense sentences was the strongest predictor of the listening comprehension scores.

Open Practices

This article has been awarded an Open Materials badge. Study materials are publicly accessible in the IRIS digital repository at http://www.iris-database.org. Learn more about the Open Practices badges from the Center for Open Science: https://osf.io/tvyxz/wiki.
Combining GP73 with liver stiffness measurements: A proof‐of‐concept for non‐invasive fibrosis assessment in antiviral‐naïve HBV patients
Authors: Weiskirchen Ralf , Tacke Frank
Published: October 2017

See Article on Page 1612
Variable Tl, Pb, and Cd concentrations and isotope compositions of enstatite and ordinary chondrites—Evidence for volatile element mobilization and decay of extinct 205Pb
Authors: Palk Emeliana , Andreasen Rasmus , Rehkämper Mark , Stunt Alison , Kreissig Katharina , Coles Barry , Schönbächler Maria , Smith Caroline
Published: October 2017

New Tl, Pb, and Cd concentration and Tl, Pb isotope data are presented for enstatite as well as L‐ and LL‐type ordinary chondrites, with additional Cd stable isotope results for the former. All three chondrite suites have Tl and Cd contents that vary by more than 1–2 orders of magnitude but Pb concentrations are more uniform, as a result of terrestrial Pb contamination. Model calculations based on Pb isotope compositions indicate that for more than half of the samples, more than 50% of the measured Pb contents are due to addition of modern terrestrial Pb. In part, this is responsible for the relatively young and imprecise Pb‐Pb ages determined for EH, L, and LL chondrites, which are hence only of limited chronological utility. In contrast, four particularly pristine EL chondrites define a precise Pb‐Pb cooling age of 4559 ± 6 Ma. The enstatite chondrites (ECs) have highly variable ε114/110Cd of between about +3 and +70 due to stable isotope fractionation from thermal and shock metamorphism. Furthermore, nearly all enstatite meteorites display ε205Tl values from −3.3 to +0.8, while a single anomalous sample is highly fractionated in both Tl and Cd isotopes. The majority of the ECs thereby define a correlation of ε205Tl with ε114/110Cd, which suggests that at least some of the Tl isotope variability reflects stable isotope fractionation rather than radiogenic ingrowth of 205Tl from 205Pb decay. Considering L chondrites, most ε205Tl values range between −4 and +1, while two outliers with ε205Tl ≤ −10 are indicative of stable isotope fractionation. Considering only those L chondrites which are least likely to feature Pb contamination or stable Tl isotope effects, the results are in accord with the former presence of live 205Pb on the parent body, with an initial 205Pb/204Pb = (1.5 ± 1.4) × 10−4, which suggests late equilibration of the Pb‐Tl system 26–113 Ma after carbonaceous chondrites (CCs). The LL chondrites display highly variable ε205Tl values from −12.5 to +14.9, also indicative of stable isotope effects. However, the data for three pristine LL3/LL4 chondrites display an excellent correlation between ε205Tl and 204Pb/203Tl. This defines an initial 205Pb/204Pb of (1.4 ± 0.3) × 10−4, equivalent to a 205Pb‐205Tl cooling age of 55 + 12/−24 Ma (31–67 Ma) after CCs.
Exploring barriers and enablers for scaling up a community‐based grain bank intervention for improved infant and young child feeding in Ethiopia: A qualitative process evaluation
Authors: Sako Binta , Leerlooijer Joanne N. , Lelisa Azeb , Hailemariam Abebe , Brouwer Inge D. , Tucker Brown Amal , Osendarp Saskia J. M.
Published: October 2017

Child malnutrition remains high in Ethiopia, and inadequate complementary feeding is a contributing factor. In this context, a community‐based intervention was designed to provide locally made complementary food for children 6–23 months, using a bartering system, in four Ethiopian regions. After a pilot phase, the intervention was scaled up from 8 to 180 localities. We conducted a process evaluation to determine enablers and barriers for the scaling up of this intervention. Eight study sites were selected to perform 52 key informant interviews and 31 focus group discussions with purposely selected informants. For analysis, we used a framework describing six elements of successful scaling up: socio‐political context, attributes of the intervention, attributes of the implementers, appropriate delivery strategy, the adopting community, and use of research to inform the scale‐up process. A strong political will, alignment of the intervention with national priorities, and integration with the health care system were instrumental in the scaling up. The participatory approach in decision‐making reinforced ownership at community level, and training about complementary feeding motivated mothers and women's groups to participate. However, the management of the complex intervention, limited human resources, and lack of incentives for female volunteers proved challenging. In the bartering model, the barter rate was accepted, but the bartering was hindered by unavailability of cereals and limited financial and material resources to contribute, threatening the project's sustainability. Scaling up strategies for nutrition interventions require sufficient time, thorough planning, and assessment of the community's capacity to contribute human, financial, and material resources.
Use of cell surface protein typing for genotyping of azole‐resistant and ‐susceptible Aspergillus fumigatus isolates in Iran
Authors: Falahatinejad Mahsa , Vaezi Afsane , Fakhim Hamed , Abastabar Mahdi , Shokohi Tahereh , Zahedi Nina , Ansari Saham , Meis Jacques F. , Badali Hamid
Published: October 2017

Aspergillus fumigatus is the leading cause of mortality in severely immunocompromised individuals. Understanding pathogen dispersion and relatedness is essential for determining the epidemiology of nosocomial infections. Therefore, the aim of this study was to investigate the diversity and putative origins of clinical and environmental azole‐susceptible and ‐resistant A. fumigatus isolates from Iran. In all, 79 isolates, including 64 azole‐susceptible and 15 ‐resistant isolates, were genotyped using the cell surface protein (CSP) gene. Seven distinct repeat types (r01, r02, r03, r04, r05, r06 and r07) and 11 different CSP variants (t01, t02, t03, t04A, t06A, t06B, t08, t10, t18A, t18B and t22) were observed. Interestingly, t06B, t18A and t18B were exclusively present in azole‐resistant isolates. The Simpson's index of diversity (D) was calculated at 0.78. Resistant isolates were genetically less diverse than azole‐susceptible isolates. However, azole‐resistant A. fumigatus without TR34/L98H were more diverse than with TR34/L98H. The limited CSP type diversity of the TR34/L98H isolates versus azole‐susceptible isolates suggests that repeated independent emergence of the TR34/L98H mechanism is unlikely. It has been suggested that CSP types might have a common ancestor that developed locally and subsequently migrated worldwide.
Role of dietary phosphate restriction in chronic kidney disease
Authors: Elder Grahame J , Malik Avya , Lambert Kelly
Published: October 2017

Aim

Patients with progressive chronic kidney disease (CKD) develop positive phosphate balance that is associated with increased cardiovascular risk and mortality. Modification of dietary phosphate is a commonly used strategy to improve outcomes but is complicated by the need for adequate dietary protein. Surprisingly, the evidence for patient‐level benefits from phosphate restriction is tenuous, and the justification for using any phosphate binder for pre‐dialysis patients is questionable.

Methods

The evidence for dietary phosphate modification was reviewed, along with the possible role of a smart phone application (app) that provides information on phosphate, sodium, potassium and nutrients in over 50 000 Australian foods. A pilot study of healthy participants assigned to dietetic advice and standard diet sheets, or dietetic advice, diet sheets and use of the smart phone app was performed.

Results

Following baseline studies, 25 participants commenced the sodium and phosphate restricted diet. After 2 weeks, both groups showed non‐significant trends to reduction in urinary phosphate and sodium. App users referred to information on the app more frequently than the control group participants referred to written instructions, found referring to the app more convenient, felt they learned more new information, were more motivated to maintain the diet and were more likely to recommend their information source to family or friends (all P < 0.05).

Conclusions

Maintaining phosphate balance remains an important goal of CKD management, although diets incorporating very low phosphate and protein contents may worsen patient outcomes. For selected patients, a smart phone app may improve dietary acceptance and compliance.
Amyotrophic lateral sclerosis and parkinsonism‐dementia complex of the Hohara focus of the Kii Peninsula: A multiple proteinopathy?
Authors: Mimuro Maya , Yoshida Mari , Kuzuhara Shigeki , Kokubo Yasumasa
Published: October 2017

The high incidence of amyotrophic lateral sclerosis (ALS) and parkinsonism‐dementia complex (PDC) has been previously known in the Kii Peninsula of Japan and in Guam. Recently, the accumulation of various proteins, such as tau, trans‐activation response DNA binding protein 43 kDa (TDP‐43), and alpha‐synuclein (αSyn), was reported in the brains of patients with ALS/PDC in Guam. To confirm whether similar findings are present in Kii ALS/PDC, we neuropathologically examined the brains and spinal cords of 18 patients with ALS/PDC (clinical diagnoses: eight ALS and 10 PDC) in Hohara Village, which is the eastern focus of Kii ALS. The average age at death was 71.6 years, and 16 patients (88.9%) had a family history of ALS/PDC. Autopsy specimens were immunohistochemically examined with antibodies against four major proteins. Neurofibrillary tangles, including ghost tangles, and tau‐positive astrocytes were distributed widely in all of the brains examined, and TDP‐43‐positive neuronal cytoplasmic inclusions were observed mainly in the limbic system. Synuclein pathology was present in 14 patients (77.8%). These patients were classified into three pathological subtypes according to the most prominent proteinopathy: the tauopathy‐dominant type, the TDP‐43 proteinopathy‐dominant type, and the synucleinopathy‐dominant type. Five patients with severe tau deposition showed clinical features of atypical parkinsonism and dementia with or without motor neuron disease. Eight patients were predominated by phosphorylated TDP‐43 inclusions and clinically showed ALS, and five patients were predominated by synuclein pathology and clinically showed signs of PDC. Based on the common characteristic tau pathology, three subtypes seemed to be pathologically continuous on a spectrum of a single disease. Thus, we conclude that ALS/PDC in the Hohara focus of the Kii Peninsula is a single disease characterized neuropathologically by a multiple proteinopathy, even though the clinical manifestations of the three subtypes differed from each other. It remains unclear whether the coexistence of the three proteinopathies was incidental or pathogenetically related.
Learning from the past: reflections on recently completed myasthenia gravis trials
Authors: Benatar Michael , Howard James F. , Barohn Richard , Wolfe Gil I. , Cutter Gary
Published: October 2017

Recently competed clinical trials of therapeutics for myasthenia gravis have varied widely in design, but also perhaps in less explicit ways. We explore ways in which these design characteristics may have influenced recruitment and results, as well as the implications for forthcoming studies. Trial eligibility criteria may inadvertently select for incident versus prevalent cases or patients with relatively mild versus more severe disease. Trial enrichment with patients who have relatively mild disease may limit the sensitivity of the trial to detect a therapeutic effect. Enrichment for patients with more severe disease may introduce confounds caused by regression toward the mean. Overly narrow eligibility may limit the generalizability of results. An exclusive focus on incident cases may hamper recruitment, as may many other factors, such as access to the experimental therapeutic treatment outside of the trial or following completion of the double‐blind treatment period. We illustrate how other design characteristics (e.g., treatment duration, strategy for steroid tapering, selection of the primary outcome, and principal analytic approach) may affect the sensitivity of a trial to demonstrate therapeutic effects. Finally, we consider the importance of placebo effects, being careful to differentiate these from therapeutic effects observed in the placebo group, and discuss how the use of combined outcome measures may minimize placebo effects.
A diagnosis and treatment gap for thiamine deficiency disorders in sub‐Saharan Africa?
Authors: Adamolekun Bola , Hiffler Laurent
Published: October 2017

Staple diets that are deficient in thiamine can result in low body thiamine levels, which may be subclinical or may manifest as a thiamine‐deficiency syndrome. In many communities in the developing countries of Africa, the staple diets of polished rice or processed cassava are deficient in thiamine, and thus the communities are at high risk for marginal or frank thiamine deficiency unless their diets are supplemented by other sources of thiamine, such as protein meals and vegetables. African communities with large numbers of individuals in low socioeconomic strata are more likely to subsist on a monotonous diet of rice or cassava with minimal or no protein supplementation and are therefore particularly at risk of thiamine‐deficiency disorders. Indeed, there is evidence of widespread biochemical thiamine deficiency from community‐based studies in Africa. The protean manifestations of thiamine deficiency disorders in the developing countries of Africa are presented in this paper. We present evidence supporting the contention that there is a diagnosis and treatment gap for thiamine‐deficiency disorders in Africa. We discuss research and clinical options for bridging the putative diagnosis and treatment gap for thiamine‐deficiency disorders in the developing countries of Africa.
Utility of preoperative Holter monitoring in children undergoing extracardiac conduit Fontan operation
Authors: Sasaki Jun , Lopez Michael M. , Baysa Sherrie J. , Kanter Ronald J. , Rossi Anthony F.
Published: October 2017

Background

In patients undergoing extracardiac conduit Fontan (ECF) who require postoperative pacing, epicardial leads are usually required because of anatomical constraints. If indicated, these could be conveniently placed at the time of ECF. We have routinely performed ambulatory 24‐hour Holter monitoring before ECF to determine the presence or absence of preoperative sinus node dysfunction, in an attempt to avoid repeat sternotomy at a later time.

Methods

We performed a retrospective study of all patients undergoing ECF from January 2000 to December 2015.

Results

Two hundred sixteen patients met inclusion criteria. Patients were separated into two groups, those with preoperative Holter monitoring (PHM, n = 150) and those without (No‐PHM, n = 66). Ten patients (4.6%) underwent permanent pacemaker implantation at the time of ECF (eight patients [5.3%] in PHM vs two patients [3.0%] in No‐PHM, P = 0.46). There were seven (3.2%) patients who underwent pacemaker implantation after ECF requiring repeat sternotomy (four patients [2.7%] in PHM vs three patients [4.5%] in No‐PHM, P = 0.47). Fourteen (6.5%) patients underwent permanent epicardial lead placement without a pulse generator at the time of ECF. None from this group underwent pacemaker implantation to date (median follow‐up of 5.7 years). The overall incidence of pacemaker implantation was 9.3% (20 patients).

Conclusions

In our series, arrhythmia disturbances requiring pacing after ECF occurred in just over 9% of patients. While PHM in those patients may help predict which patients might require postoperative pacing, this approach did not result in a significant decrease in those patients requiring repeat sternotomy for pacemaker implantation.
Nurse‐driven analgesia and sedation in pediatric patients with univentricular hearts requiring extracorporeal life support after first‐stage palliation surgery: A pilot study
Authors: Michel Jörg , Hofbeck Michael , Gerbig Ines , Icheva Vanya , Heimberg Ellen , Jost Walter , Schlensak Christian , Kumpf Matthias , Blumenstock Gunnar , Neunhoeffer Felix
Published: October 2017

Background

Few data are available regarding requirements of sedation and analgesia in children during extracorporeal life support.

Aims

The aim of this study was to evaluate if children with functionally univentricular hearts on extracorporeal life support after first‐stage palliation surgery have higher requirement of analgesics and sedatives compared with children without extracorporeal life support using a goal‐directed nurse‐driven analgesia and sedation protocol.

Methods

This prospective observational matched case‐control pilot study was conducted at a cardiac pediatric intensive care unit of a tertiary referral center. Seventeen patients with functionally univentricular hearts including hypoplastic left heart syndrome who were on extracorporeal life support after first‐stage palliation surgery were enrolled from July 2012 to January 2017. Seventeen matched patients served as controls. Doses of morphine, midazolam, clonidine, and muscle relaxants as well as sedation scores (COMFORT behavior scale and the nurse interpretation of sedation scale) were assessed according to a nurse‐driven protocol every 8 hours up to 120 hours after first‐stage palliation surgery.

Results

Sedation scores were equal in the extracorporeal life support group and in the control group at most points in time. There was no significant difference in cumulative doses of morphine and midazolam. However, children of the extracorporeal life support group received higher doses of midazolam and morphine at some points in time.

Conclusion

A nurse‐driven protocol for analgesia and sedation of children with extracorporeal life support is feasible. Patients with extracorporeal life support do not need deeper sedation levels and have not higher cumulative sedation requirements than children without extracorporeal life support.
Interpreting the Effectiveness of Opioids and Pregabalin for Pain Severity, Pain Interference, and Fatigue in Fibromyalgia Patients
Authors: Davis Fred , Gostine Mark , Roberts Bradley A. , Risko Rebecca , Cappelleri Joseph C. , Sadosky Alesia
Published: October 2017

Objective

To evaluate the effectiveness of opioids and/or pregabalin on patient‐reported outcomes among fibromyalgia (FM) patients based on levels of improvement.

Methods

A total of 1,421 FM patients were identified, with 3,082 observational periods of opioids with or without pregabalin use between April 2008 and February 2015. Patients were categorized by opioids, and pregabalin with and without opioids; opioids were designated by morphine equivalent dose (MED) of ≤ 20 (low MED), > 20 to < 100 (moderate MED), ≥ 100 (high MED), and pregabalin doses of ≤ 150 mg, 151 to 300 mg, and 301 to 450 mg. Proportions of patients meeting clinically relevant thresholds of ≥ 30% and ≥ 50% improvement for pain interference (ability to enjoy life; activity; mood; relationships; sleep), pain severity, and fatigue were compared among treatments, and area under the curve (AUC) for improvement and worsening of effects was determined, enabling ranking of treatments. Further analysis compared pregabalin doses.

Results

Pregabalin without opioids resulted in the highest proportions of patients with ≥ 30% improvement on all pain items and pain interference with “ability to enjoy life,” “activity” “mood,” and “sleep.” For the ≥ 50% threshold, pregabalin alone was highest for all pain interference items and for “average pain” and “worst pain.” Pregabalin was consistently lowest across thresholds for fatigue, but showed better results combined with moderate MED opioids. Pregabalin doses recommended for treatment of FM (151 to 450 mg) generally resulted in the highest proportion of patients achieving thresholds relative to opioids. The AUC results were consistent with thresholds; pregabalin without opioids resulted in the greatest benefits with regard to improvement, with the highest ranking for overall improvement and overall effects.

Conclusion

Pregabalin without opioids provided the most favorable outcomes overall based on ≥ 30% and ≥ 50% improvement thresholds and AUC, with support for moderate MED opioids + pregabalin in patients suffering from fatigue. While most patients took less than recommended pregabalin doses, higher doses may lead to improved outcomes.
Phenological match drives pollen‐mediated gene flow in a temporally dimorphic tree
Authors: Gleiser G. , Chybicki I. J. , González‐Martínez S. C. , Aizen M. A.
Published: October 2017

Variation in flowering phenology is common in natural populations, and is expected to be, together with inter‐mate distance, an important driver of effective pollen dispersal. In populations composed of plants with temporally separated sexual phases (i.e. dichogamous or heterodichogamous populations), pollen‐mediated gene flow is assumed to reflect phenological overlap between complementary sexual phases. In this study, we conducted paternity analyses to test this hypothesis in the temporally dimorphic treeAcer opalus.

We performed spatially explicit analyses based on categorical and fractional paternity assignment, and included tree size, pair‐wise genetic relatedness and morph type as additional predictors. Because differences between morphs in flowering phenology may also influence pollination distances, we modelled separate pollen dispersal kernels for the two morphs.

Extended phenological overlap between male and female phases (mainly associated with inter‐morph crosses) resulted in higher siring success after accounting for the effects of genetic relatedness, morph type and tree size, while reduced phenological overlap (mainly associated with intra‐morph crosses) resulted in longer pollination distances achieved. Siring success also increased in larger trees.

Mating patterns could not be predicted by phenology alone. However, as heterogeneity in flowering phenology was the single morph‐specific predictor of siring success, it is expected to be key in maintaining the temporal dimorphism inA. opalus, by promoting not only a prevalent pattern of inter‐morph mating, but also long‐distance pollination resulting from intra‐morph mating events.
Biogeography and diversification of Holarctic water striders: Cenozoic temperature variation, habitat shifting and multiple intercontinental dispersals
Authors: YE ZHEN , ZHEN YAHUI , DAMGAARD JAKOB , CHEN PINGPING , ZHU LIN , ZHENG CHENGUANG , BU WENJUN
Published: October 2017

It is now rare to find a semi‐aquatic organism group with which to vigorously test whether their diversification model and distribution pattern are closely related to the Cenozoic temperature variation. This hypothesis is explored for water striders of the generaAquariusSchellenberg,GerrisFabricius andLimnoporusStål, which comprise a monophyletic clade with primarily Holarctic distribution. We sample almost 90% of the currently recognizedAquarius,GerrisandLimnoporusspecies. Five DNA fragments from 62 species are used to reconstruct a phylogram. Divergence time is estimated using Bayesian relaxed‐clock method and three fossil calibrations. We investigate diversification dynamics, biogeography and ancestral state reconstruction by using maximum‐likelihood, Bayesian and parsimony approaches. Our results showed that the crown of the three genera originated and underwent an initial diversification in Asia at 72 Ma (HPD: 59–86 Ma) in the Late Cretaceous, subsequently expanding into other regions via dispersal. The Bering Land Bridge was the major migration route between Eurasia and North America but was interrupted before the early Oligocene (34 Ma). Ancestors most likely used lentic habitats, and a minimum of two independent shifts to lotic habitats occurred in the initial diversification. Cenozoic temperature variation regulated the evolutionary history of Holarctic water striders of the generaAquarius,GerrisandLimnoporus. Temperature warming during Stage I (52–66 Ma) was associated with the disappearance of shallow lentic habitats; this phenomenon forced certain lentic lineages to colonize new lotic habitats and promoted the diversification of lineages. Temperature cooling during Stage II (after 34 Ma) was associated with the fragmentation of water habitats of the ‘mixed‐mesophytic’ belt, resulting in the extinction of historical taxa and influencing close lineages that shaped the present disjunct Eurasian–North American distribution.
Sequence‐based typing identification of the novel HLA‐C*07:565 variant in a Chinese family
Authors: Wang J. , Zhang Y. , Li Q. , Ru K. , Wang X.
Published: October 2017

HLA‐C*07:565 differs from HLA‐C*07:02:01:01 (400C‐>T, exon 3, L110F).
Disagreeing with Confidence
Authors: Besong Brian
Published: October 2017

Does having an initially high level of justified confidence in a belief vindicate remaining steadfast in the face of disagreement? According to one prominent view in the literature, namely Jennifer Lackey's justificationist position, the answer is yes so long as one also has personal information that provides a symmetry‐breaker. In this article, I raise a problem for the justificationist view. On the most straightforward reading of the justificationist position, personal informationalwaysprovides a symmetry‐breaker in a peer dispute over a belief in which one has high justified confidence. However, this position is implausibly strong because it renders epistemically permissible a dogmatic attitude in a relevant set of peer disagreements. Alternatively, weaker readings of the view fail to provide a perspicuous account of when high justified confidence matters in a disagreement.
Treatment of self‐poisoning at a tertiary‐level hospital in Bangladesh: cost to patients and government
Authors: Verma Vasundhara , Paul Sujat , Ghose Aniruddha , Eddleston Michael , Konradsen Flemming
Published: October 2017

Objectives

Approximately 10 000 people die from suicide annually in Bangladesh, many from pesticide poisoning. We aimed to estimate financial costs to patients and health services of treating patients with self‐poisoning.

Methods

Data on direct costs to families, sources of funds for treatment and family wealth were collected prospectively over a one‐month period in 2016 at the tertiary Chittagong Medical College Hospital, Bangladesh. Aggregate operational costs to the government were calculated using annual budget, bed occupancy and length‐of‐stay data.

Results

Agrochemicals were the most common substances ingested (58.8%). Median duration of stay and of illness was 2 and 5 days, respectively. Median total cost to patients was conservatively estimated at US$ 98.40, highest in agrochemical poisoning (US$ 179.50), with the greatest cost due to medicines and equipment. Misdiagnosis as organophosphorus poisoning in 17.0% of agrochemical cases resulted in increased cost to patients. Only 51.9% of patients had indicators of wealth; 78.1% borrowed money to cover costs. Conservatively estimated median healthcare costs (US$ 21.30 per patient) were markedly lower than costs to patients.

Conclusions

Cost to patients of treating a case of agrochemical poisoning was approximately three times the cost of one month's essential items basket. Incorrect diagnosis at admission costs families substantial sums of money and increased length of stay; it costs the national government an estimated US$ 80 428.80 annually. Widespread access to a list of pesticides used in self‐poisoning plus greater focus on training doctors to better manage different forms of agrochemical poisoning should reduce the financial burden to patients and healthcare systems.
The management of vulval itching caused by benign vulval dermatoses
Authors: Nunns David , Simpson Rosalind , Watson Andrew , Murphy Ruth
Published: October 2017

Key content

This article will cover key points in patient assessment, vulval examination and treatment of vulval disease, specifically dermatological conditions.

Often, simple measures can benefit the patient (e.g. use of emollients). However, many women have complex disease with more than one condition, so careful assessment and individualised management is essential.

Some gynaecologists have unmet training needs in the assessment and management of vulval skin disease. It is important to assess patients and then refer difficult cases and non‐responders to a vulval service for a multidisciplinary opinion.

Learning objectives

To increase skills in patient assessment, vulval examination and treatment of common vulval diseases.

To improve clinical outcomes for women by increasing basic and intermediate knowledge and skills of vulval disease according to the national evidence base.

Ethical issues

Clinicians managing vulval disease must be sensitive and willing to ask women about sexual problems associated with their disease.

All clinicians, regardless of experience or level of seniority, should have an understanding of the relevant conditions underlying these symptoms.
Donor‐specific individuality of red blood cell performance during storage is partly a function of serum uric acid levels
Authors: Tzounakas Vassilis L. , Karadimas Dimitrios G. , Anastasiadi Alkmini T. , Georgatzakou Hara T. , Kazepidou Eleftheria , Moschovas Dimitris , Velentzas Athanassios D. , Kriebardis Anastasios G. , Zafeiropoulos Nikolaos E. , Avgeropoulos Apostolos , Lekka Marilena , Stamoulis Konstantinos E. , Papassideri Issidora S. , Antonelou Marianna H.
Published: October 2017

BACKGROUND

Previous investigations in leukoreduced units of red blood cells (RBCs) in mannitol additive solution revealed the close association of uric acid (UA) levels in vivo with the susceptibility of RBCs to storage lesion markers. In this study, we examined whether UA has a similar correlation with the capability of RBCs to cope with the oxidative provocations of storage under different conditions, namely, in CPDA‐1 and in the absence of leukoreduction.

STUDY DESIGN AND METHODS

The UA‐dependent antioxidant capacity of the supernatant was measured in nonleukoreduced units of RBCs in CPDA (n = 47). The possible effect of UA variability on the storage lesion profile was assessed by monitoring several physiologic properties of RBCs and supernatant, including cell shape, reactive oxygen species, and size distribution of extracellular vesicles, in units exhibiting the lowest or highest levels of UA activity (n = 16) among donors, throughout the storage period.

RESULTS

In stored RBC units, the UA‐dependent antioxidant activity of the supernatant declined as a function of storage duration but always in strong relation to the UA levels in fresh blood. Contrary to units of poor‐UA activity, RBCs with the highest levels of UA activity exhibited better profile of calcium‐ and oxidative stress–driven modifications, including a significant decrease in the percentages of spherocytes and of 100‐ to 300‐nm‐sized vesicles, typically associated with the exovesiculation of stored RBCs.

CONCLUSION

The antioxidant activity of UA is associated with donor‐specific differences in the performance of RBCs under storage in nonleukoreduced CPDA units.
Comparison of albumin, colloid osmotic pressure, von Willebrand factor, and coagulation factors in canine cryopoor plasma, cryoprecipitate, and fresh frozen plasma
Authors: Culler Christine A. , Iazbik Cristina , Guillaumin Julien
Published: October 2017

Objective

To compare albumin concentrations, coagulation factors activity, and colloid osmotic pressure (COP) of cryoprecipitate (CRYO) and cryopoor plasma (CPP) to that of source fresh frozen plasma (FFP).

Design

Prospective in vitro study.

Setting

University teaching hospital.

Animals

Ten healthy, non‐Greyhound dogs enrolled in an academic teaching hospital blood donor program.

Interventions

Fresh blood was obtained from canine blood donors and separated into FFP and packed red blood cells. The source FFP was further separated into CRYO and CPP. Albumin and fibrinogen concentrations, COP, activities of coagulation factors II, V, VII, VIII, IX, X, and von Willebrand factor (vWf) were assessed for each FFP, CRYO, and CPP.

Measurements and Main Results

The mean albumin concentration and COP in CPP were significantly higher compared with those found in FFP, with 31.7 g/L (±6) in CPP compared to 28.9 g/L (±0.5) in FFP (P< 0.001) and 14.5 mm Hg (±0.7) in CPP compared to 12.7 mm Hg (±0.3) in FFP (P= 0.03), respectively. CRYO had significantly higher concentrations of fibrinogen (median 3.46 g/L, 95% CI 2.65–4.27), and higher activities of factor VIII (mean activity 427.0%, ±95.4) and vWf (mean activity 504.7%, ±41.39) as compared to the other products. The activities of vitamin K dependent factors II, VII, and X were similar in CPP compared to FFP, although factor IX activity was lower in CPP. There was no significant difference in factor II or VII activities between the 3 products.

Conclusions

The mean albumin concentration and COP were highest in CPP, suggesting that CPP may be a potential alternative to FFP for oncotic support and albumin replacement. CRYO contained higher activities of vWf and factor VIII than other products and could be used to treat vWf deficiency and hemophilia A. As vitamin K dependent coagulation factors II, VII, and X in CPP were similar to FFP, CPP may be an option for replacement of most of vitamin K dependent factors.
Reductions in margin length after excision of grade II mast cell tumors and grade I and II soft tissue sarcomas in dogs
Authors: Milovancev Milan , Townsend Katy L. , Bracha Shay , Gorman Elena , Curran Kaitlin , Russell Duncan S.
Published: October 2017

Objective

Quantify changes in the circumferential lengths of surgical margins of resected canine mast cell tumors (MCT) and soft tissue sarcomas (STS) between the time of collection and histopathology.

Study design

Prospective, hypothesis‐driven, clinical study.

Sample population

Two hundred and thirty‐seven margins from 69 excised tumors (50 MCT and 19 STS) in 51 client‐owned dogs.

Methods

The lengths of surgical margins were recorded (eg, cranial, caudal, dorsal, and ventral) for each tumor at 5 time points: intraoperatively (in vivo), immediately after excision (ex vivo), after formalin fixation (postfixation), once mounted on glass slides (subgross), and as histologically tumor‐free margins (HTFMs).

Results

Compared to in vivo dimensions, the length of surgical margins at each processing step (ie, ex vivo, postfixation, subgross, and HTFM) was reduced by a median of 3.0, 5.0, 6.0, and 8.8 mm for MCT; 2.5, 2.0, 5.0, and 5.0 mm for STS. All processing steps resulted in significant reductions among MCT samples (P < .0001), except between postfixation vs subgross, and for STS samples (P < .0001), except between ex vivo vs postfixation and subgross vs HTFM. The maximum reduction in the total length of margins (from in vivo to HTFM) was 29.6 and 24.2 mm for MCT and STS, respectively.

Conclusion

Surgical margin length reductions occur due to a combination of physical factors (eg, tissue elasticity, myofibril contraction, and histologic processing) and biological factors (eg, microscopic tumor infiltration into the grossly normal surgical margin).

Clinical significance

These data provide information relevant to evidence‐based surgical planning and may influence patient morbidity in the most commonly encountered cutaneous malignancies of dogs.