bluuebunny/crossref_metadata_2025 huggingface dataset:
Response of Mung Bean (Vigna radiata (L.) R. Wilczek) to an Increasing Natural Temperature Gradient under Different Crop Management Systems
Authors: Malaviarachchi M. A. P. W. K. , De Costa W. A. J. M. , Kumara J. B. D. A. P. , Suriyagoda L. D. B. , Fonseka R. M.
Published: April 2015

Increasing temperatures pose a significant threat to crop production in the tropics. A field experiment was conducted with mung bean at three locations in Sri Lanka representing an increasing temperature gradient (24.4–30.1 °C) during two consecutive seasons to (i) determine the response of mung bean to increasing temperature and (ii) test a selected set of crop management practices aimed at decreasing essential inputs such as water, synthetic pesticides and inorganic nitrogen fertilizer. The control treatment (T1) consisted of standard crop management including irrigation, chemical crop protection and inorganic fertilizer application. Adaptation system 1 (T2) included mulching with rice straw at 8 t ha−1 with 30 % less irrigation and crop protection and nutrient management as in T1. Adaptation system 2 (T3) included crop protection using a pretested integrated pest management package with water and nutrient management as in T2. In adaptation system 3 (T4), 25 % of the crop's nitrogen requirement was given as organic manure (compost) at 0.8 t ha−1 while 75 % was given as inorganic fertilizer with water management and crop protection as in T3. Durations of both pre‐ and post‐flowering phases were reduced with increasing temperature. In the warmer (25.4–30.1 °C) yala season, seed yield (Y) of T1 decreased with increasing temperature at 366 kg ha−1 °C−1. However, in maha season, Y did not show a significant relationship across the narrower temperature gradient from 24.4 to 25.8 °C. Pooling the data from both seasons showed a second‐order polynomial response with an optimum temperature of 26.5 °C. In addition to shortened durations, reduced crop growth rates and reduced pod numbers per plant were responsible for yield reductions at higher temperatures. In yala, yields of all adaptation systems at all locations were on par with yields of the respective controls. Furthermore, yala yields of T2 and T3 were less sensitive than T1 to increasing temperatures (265 and 288 kg ha−1 °C−1). In maha, T3 and T4 had greater yields than the control at the relatively cooler site while having lower yields than the control at the warmer site. Maha yields of T2 were on par with the control at both temperature regimes. While demonstrating the significant temperature sensitivity of mung bean yields, results of the present work showed that components of the tested adaptation systems could be promoted among smallholder farmers in Asia, especially in view of their long‐term environmental benefits and contributions to sustainable agriculture in a warmer and drier future climate.
Informal Support and Burden among Parents of Adults with Intellectual and/or Developmental Disabilities
Authors: Robinson Suzanne , Weiss Jonathan A. , Lunsky Yona , Ouellette‐Kuntz Hélène
Published: April 2015

Background

Parents often play a lifelong role in supporting their sons and daughters with intellectual and/or developmental disabilities (IDD). There is a need to better understand parent resources, particularly when the individual with IDD has behaviour problems, as the latter has consistently been linked to parental burden.

Methods

The current study aimed to investigate the relationship between the behaviour support needs of 212 adults with IDD and parental burden, and whether perceived helpfulness of informal supports moderated this relationship. The helpfulness of individual sources of informal support was also explored.

Results

Informal support was negatively related to burden, although it did not act as a moderator. Individual sources varied in terms of how they were related to burden, but none acted as moderators.

Conclusions

Although informal social support appears to be important to parents and may help alleviate burden, it does not appear to act as a moderator as anticipated.
Does fragmentation of wetlands affect gene flow in sympatric Acrocephalus warblers with different migration strategies?
Authors: Ceresa Francesco , Belda Eduardo J. , Kvist Laura , Rguibi‐Idrissi Hamid , Monrós Juan S.
Published: April 2015

Wetlands are naturally patchy habitats, but patchiness has been accentuated by the extensive wetlands loss due to human activities. In such a fragmented habitat, dispersal ability is especially important to maintain gene flow between populations. Here we studied population structure, genetic diversity and demographic history of Iberian and North African populations of two wetland passerines, the Eurasian reed warbler Acrocephalus scirpaceus and the moustached warbler Acrocephalus melanopogon. These species are closely related and sympatric in our study sites, but the reed warbler is a widespread long‐distance migrant while the moustached warbler's breeding range is patchier and it is resident or migrates over short distances. Using microsatellite and mtDNA data, we found higher differentiation in moustached than in reed warblers, indicating higher dispersal capability of the latter species. Our results also suggest that the sea limits dispersal in the moustached warbler. However, we found evidence of gene flow between the study sites in both species, indicating a capability to compensate for habitat fragmentation. In most cases, the gene flow was restricted, possibly because of the large distances between study sites (from ca 290 to 960 km) or breeding site fidelity. The reed warbler had higher haplotype diversity, likely due to dispersal from different populations, past admixture event and a larger population size. We found also signs of postglacial population growth for both species and evidence of a recent colonization or re‐colonization of the Mallorca Island by the moustached warbler.
Re‐colonization by common eiders Somateria mollissima in the Aleutian Archipelago following removal of introduced arctic foxes Vulpes lagopus
Authors: Petersen Margaret R. , Byrd G. Vernon , Sonsthagen Sarah A. , Sexson Matthew G.
Published: April 2015

Islands provide refuges for populations of many species where they find safety from predators, but the introduction of predators frequently results in elimination or dramatic reductions in island‐dwelling organisms. When predators are removed, re‐colonization for some species occurs naturally, and inter‐island phylogeographic relationships and current movement patterns can illuminate processes of colonization. We studied a case of re‐colonization of common eiders Somateria mollissima following removal of introduced arctic foxes Vulpes lagopus in the Aleutian Archipelago, Alaska. We expected common eiders to resume nesting on islands cleared of foxes and to re‐colonize from nearby islets, islands, and island groups. We thus expected common eiders to show limited genetic structure indicative of extensive mixing among island populations. Satellite telemetry was used to record current movement patterns of female common eiders from six islands across three island groups. We collected genetic data from these and other nesting common eiders at 14 microsatellite loci and the mitochondrial DNA control region to examine population genetic structure, historical fluctuations in population demography, and gene flow. Our results suggest recent interchange among islands. Analysis of microsatellite data supports satellite telemetry data of increased dispersal of common eiders to nearby areas and little between island groups. Although evidence from mtDNA is suggestive of female dispersal among island groups, gene flow is insufficient to account for recolonization and rapid population growth. Instead, near‐by remnant populations of common eiders contributed substantially to population expansion, without which re‐colonization would have likely occurred at a much lower rate. Genetic and morphometric data of common eiders within one island group two and three decades after re‐colonization suggests reduced movement of eiders among islands and little movement between island groups after populations were re‐established. We predict that re‐colonization of an island group where all common eiders are extirpated could take decades.
Ambulatory Blood Pressure Monitoring–Derived Short‐Term Blood Pressure Variability in Primary Aldosteronism
Authors: Grillo Andrea , Bernardi Stella , Rebellato Andrea , Fabris Bruno , Bardelli Moreno , Burrello Jacopo , Rabbia Franco , Veglio Franco , Fallo Francesco , Carretta Renzo
Published: April 2015

The aim of this study was to investigate the short‐term blood pressure (BP) variability (BPV) derived from ambulatory blood pressure monitoring (ABPM) in patients with primary aldosteronism (PA), either idiopathic hyperaldosteronism (IHA) or aldosterone‐producing adenoma (APA), in comparison with patients with essential hypertension (EH) and normotensive (NT) controls. Thirty patients with PA (16 with IHA and 14 with APA), 30 patients with EH, and 30 NT controls, matched for sex, age, body mass index, and antihypertensive therapy, were studied. The standard deviation (SD) of 24‐hour, daytime, and nighttime BP; 24‐hour weighted SD of BP; and 24‐hour BP average real variability were not different between patients with PA and those with EH (P=not significant). All BPV indices were higher in patients with PA, either IHA or APA subtypes, and patients with EH, compared with NT controls (P<.001 to P<.05). ABPM‐derived short‐term BPV is increased in patients with PA, and it may represent an additional cardiovascular risk factor in this disease. The role of aldosterone excess in BPV has to be clarified.
Physician perspectives in the management of psoriasis and psoriatic arthritis: results from the population‐based Multinational Assessment of Psoriasis and Psoriatic Arthritis survey
Authors: van de Kerkhof P.C.M. , Reich K. , Kavanaugh A. , Bachelez H. , Barker J. , Girolomoni G. , Langley R.G. , Paul C.F. , Puig L. , Lebwohl M.G.
Published: April 2015

Background

Available literature on psoriasis and psoriatic arthritis (PsA) demonstrates a tremendous burden of disease and suggests underdiagnosis and undertreatment.

Objective

To obtain real‐world physician perspectives on the impact of psoriasis and PsA and its treatment on patients' daily lives, including perceptions of, and satisfaction with, current therapies.

Methods

The Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) surveyed dermatologists (n = 391) and rheumatologists (n = 390) in North America (Canada and the United States) and Europe (France, Germany, Italy, Spain and United Kingdom).

Results

Dermatologists classified 20.3% and 25.7% of their patients as having severe psoriasis and severe PsA respectively; rheumatologists indicated that 48.4% of their PsA patients had active disease. Of the psoriasis patients complaining of joint pain, only 33.0% had a diagnosis of PsA. An impact on daily activities or social/emotional well‐being was recognized by 57.2% to 79.3% of physicians. In patients with moderate‐to‐severe psoriasis, dermatologists reported 74.9% were receiving topical therapy, 19.5% conventional oral therapy and 19.6% biologics. Dermatologists and rheumatologists reported similar rates of topical (≈45%) and biologic (≈30%) therapy utilization for their PsA patients; conventional oral therapy was more often prescribed by rheumatologists (63.4%) vs. dermatologists (35.2%). Reasons for not initiating or maintaining systemic therapies were related to concerns about long‐term safety, tolerability, efficacy and costs (biologics).

Conclusion

Physicians in North America and Europe caring for patients with psoriasis and PsA acknowledge unmet treatment needs, largely concerning long‐term safety/tolerability and efficacy of currently available therapies; evidence suggests underdiagnosis of PsA and undertreatment of psoriasis among dermatologists.
New kid on the block? Community nurses’ experiences of caring for sick children at home
Authors: Samuelson Sarah , Willén Charlotta , Bratt Ewa‐Lena
Published: April 2015

Aims and objectives

To investigate the experiences of Swedish community nurses in caring for sick children at home, as this is a growing population of patients in community care.

Background

There is international consensus that sick children should receive care in their homes as far as possible. Home health care allows the family to stay together while the child is undergoing treatment and thus reduces strain on the family. However, it can also be demanding for parents to take on increased responsibilities for their sick child. Children as a patient group is a relatively new phenomenon in community home health care in Sweden and represents a small part of the community nurse responsibilities, making it difficult to accumulate experience.

Design

A qualitative descriptive design.

Methods

In‐depth interviews with twelve nurses in community health care. Qualitative content analysis was used.

Results

‘Feeling confident in order to instil confidence’ was key in nurses’ experiences. Two main themes emerged: ‘Building a trusting relationship with the family’ and ‘Feeling confident in the role as caregiver’. Nurses aimed at creating a trusting nursing relationship and working closely with parents. The nurses’ feeling of confidence in their role as caregivers depended on the support they received and the knowledge they had.

Conclusion

Many community nurses felt unconfident about caring for children at home but experienced it as manageable when peer support and a distinct collaboration with the paediatric clinic/hospital were present. The ongoing shift from hospital to home care urges paediatric clinics/hospitals and community health care to develop formal policies of transmural collaboration to train and support home nurses to deliver adequate care to sick children and their families at home and safeguard good outcomes.

Relevance to clinical practice

The implication of the study may contribute to efforts being made to extend and improve cooperation between paediatric clinics/hospitals and community health care.
The enantioselective population pharmacokinetics of intravenous ketorolac in children using a stereoselective assay suitable for microanalysis
Authors: Mohammed Baba S , Engelhardt Thomas , Hawwa Ahmed F , Cameron Garry A , McLay James S
Published: April 2015

Objective

To describe the effect of age and body size on enantiomer selective pharmacokinetic (PK) of intravenous ketorolac in children using a microanalytical assay.

Methods

Blood samples were obtained at 0, 15 and 30 min and at 1, 2, 4, 6, 8 and 12 h after a weight-dependent dose of ketorolac. Enantiomer concentration was measured using a liquid chromatography tandem mass spectrometry method. Non-linear mixed-effect modelling was used to assess PK parameters.

Key findings

Data from 11 children (1.7–15.6 years, weight 10.7–67.4 kg) were best described by a two-compartment model for R(+), S(−) and racemic ketorolac. Only weight (WT) significantly improved the goodness of fit. The final population models were CL = 1.5 × (WT/46)0.75, V1 = 8.2 × (WT/46), Q = 3.4 × (WT/46)0.75, V2 = 7.9 × (WT/46), CL = 2.98 × (WT/46), V1 = 13.2 × (WT/46), Q = 2.8 × (WT/46)0.75, V2 = 51.5 × (WT/46), and CL = 1.1 × (WT/46)0.75, V1 = 4.9 × (WT/46), Q = 1.7 × (WT/46)0.75 and V2 = 6.3 × (WT/46)for R(+), S(−) and racemic ketorolac.

Conclusions

Only body weight influenced the PK parameters for R(+) and S(−) ketorolac. Using allometric size scaling significantly affected the clearances (CL, Q) and volumes of distribution (V1, V2).
Pharmacological and neuroprotective profile of an essential oil derived from leaves of A
loysia citrodora Palau
Authors: Abuhamdah Sawsan , Abuhamdah Rushdie , Howes Melanie-Jayne R , Al-Olimat Suleiman , Ennaceur Abdel , Chazot Paul L
Published: April 2015

Objectives

The Jordanian ‘Melissa’, (Aloysia citrodora) has been poorly studied both pharmacologically and in the clinic. Essential oils (EO) derived from leaves of A. citrodora were obtained by hydrodistillation, analysed by gas chromatography-mass spectrometry (GC-MS) and were investigated for a range of neurobiological and pharmacological properties, as a basis for potential future use in drug discovery.

Methods

A selection of central nervous system (CNS) receptor-binding profiles was carried out. Antioxidant activity and ferrous iron-chelating assays were adopted, and the neuroprotective properties of A. citrodora EO assessed using hydrogen peroxide-induced and β-amyloid-induced neurotoxicity with the CAD (Cath.-a-differentiated) neuroblastoma cell line.

Key findings

The major chemical components detected in the A. citrodora EOs, derived from dried and fresh leaves, included limonene, geranial, neral, 1, 8-cineole, curcumene, spathulenol and caryophyllene oxide, respectively. A. citrodora leaf EO inhibited [3H] nicotine binding to well washed rat forebrain membranes, and increased iron-chelation in vitro. A. citrodora EO displays effective antioxidant, radical-scavenging activities and significant protective properties vs both hydrogen peroxide- and β-amyloid-induced neurotoxicity.

Conclusions

A . citrodora EO displays a range of pharmacological properties worthy of further investigation to isolate the compounds responsible for the observed neuroactivities, to further analyse their mode of action and determine their clinical potential in neurodegenerative diseases.
Crystallizing the Definition of Underactive Bladder Syndrome, a Common but Under‐recognized Clinical Entity
Authors: CHAPPLE Christopher R. , OSMAN Nadir I.
Published: April 2015

Detrusor underactivity (DU) is an important contributor to lower urinary tract symptoms (LUTS). While DU has been defined in the literature in urodynamic terms, current definitions lack specific parameters. In addition, the clinical syndrome associated with and manifesting itself as DU, underactive bladder (UAB), has not been well defined in the literature. In the absence of a precise definition of UAB, it is difficult to appreciate the true nature and burden of this condition. We review the evidence regarding the epidemiology, pathogenesis, diagnosis, and treatment of DU and UAB and discuss the challenges in gathering data in the absence of precise definitions. DU may be idiopathic or caused by ageing, medications, or a number of causes of neurogenic, myogenic, or iatrogenic origin. Treatments are largely palliative due to a lack of curative options, and include watchful waiting, catheterization, medications, and surgical interventions. In light of the evidence available in the literature, we propose that a new symptom‐based definition of UAB syndrome should be developed as a first step in furthering more standardized research. Further discussion on this proposed definition to reach expert consensus will enable researchers to gather more robust data, allowing greater insights into DU and UAB diagnosis and treatment.
Role of Arabidopsis AtPI4Kγ3, a type II phosphoinositide 4‐kinase, in abiotic stress responses and floral transition
Authors: Akhter Salina , Uddin Mohammad N. , Jeong In S. , Kim Dae W. , Liu Xiao‐Min , Bahk Jeong D.
Published: April 2015

Phosphoinositides (PIs) are essential metabolites which are generated by various lipid kinases and rapidly respond to a variety of environmental stimuli in eukaryotes. One of the precursors of important regulatory PIs, phosphatidylinositol (PtdIn) 4‐phosphate, is synthesized by PtdIns 4‐kinases (PI4K). Despite its wide distribution in eukaryotes, its role in plants remains largely unknown. Here, we show that the activity of AtPI4Kγ3 gene, an Arabidopsis (Arabidopsis thaliana) type II PtdIn 4‐kinase, is regulated by DNA demethylation and some abiotic stresses. AtPI4Kγ3 is targeted to the nucleus and selectively bounds to a few PtdIns. It possessed autophosphorylation activity but unexpectedly had no detectable lipid kinase activity. Overexpression of AtPI4Kγ3 revealed enhanced tolerance to high salinity or ABA along with inducible expression of a host of stress‐responsive genes and an optimal accumulation of reactive oxygen species. Furthermore, overexpressed AtPI4Kγ3 augmented the salt tolerance of bzip60 mutants. The ubiquitin‐like domain of AtPI4Kγ3 is demonstrated to be essential for salt stress tolerance. Besides, AtPI4Kγ3‐overexpressed plants showed a late‐flowering phenotype, which was caused by the regulation of some flowering pathway integrators. In all, our results indicate that AtPI4Kγ3 is necessary for reinforcement of plant response to abiotic stresses and delay of the floral transition.
Longitudinal stability of medication adherence among adolescent solid organ transplant recipients
Authors: Loiselle Kristin A. , Gutierrez‐Colina Ana M. , Eaton Cyd K. , Simons Laura E. , Devine Katie A. , Mee Laura L. , Blount Ronald L.
Published: April 2015

Solid organ transplantation requires ongoing adherence to immunosuppressants and other medications. Although adolescence is a risk factor for poor medication‐taking, little is known about the patterns of adherence within individuals over time. This study aimed to examine the stability of adherence over time using three different assessment techniques. Sixty‐six AYA transplant recipients and/or their caregiver completed interviews of adherence at baseline and at least one yr later. Serum immunosuppressant assay levels were collected via medical chart review. Non‐adherence percentages based on AYA report, caregiver report, and bioassay did not differ from Time 1 to Time 2. However, correlations for these measures across time were non‐significant. Further, the majority of AYAs shifted to a different adherence category from Time 1 to Time 2. Overall, these results demonstrate individual variability in non‐adherence over the course of adolescence and young adulthood and highlight the importance of frequent assessment across time for solid organ transplant recipients.
In‐orbit geometric calibration and validation of ZY‐3 three‐line cameras based on CCD‐detector look angles
Authors: Cao Jinshan , Yuan Xiuxiao , Gong Jianya
Published: April 2015

A simple and feasible orientation method for the three‐line cameras of the ZiYuan‐3 (ZY‐3) satellite is introduced. The method calibrates the CCD‐detector look angles in the attitude determination reference (ADR) coordinate system rather than modifying the laboratory‐calibrated orientation parameters, which are not necessary for the geometric calibration. Additionally, the unknown parameters of the model are virtually uncorrelated. Experimental results show that the direct georeferencing accuracy of ZY‐3 nadir images have been improved from the kilometre level to better than 9 m in planimetry, and that of the forward‐and‐backward stereopair was also raised to better than 18 m in plan and 4 m in height. After a bundle adjustment using four ground control points, a higher accuracy of about 3·4 m in plan and 1·6 m in height was achieved.
Using dynamics of forced expiration to identify COPD where conventional criteria for the FEV1/FVC ratio do not match
Authors: Topalovic Marko , Exadaktylos Vasileios , Decramer Marc , Berckmans Daniel , Troosters Thierry , Janssens Wim
Published: April 2015

Background and objective

The definition of chronic obstructive pulmonary disease (COPD) based on a fixed forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio or on the lower limits of FEV1/FVC of a healthy reference population is the subject of continuous debate. We explored whether dynamics of forced expiratory flow decline on spirometry can identify subjects with and without COPD when the two key diagnostic criteria are discordant.

Methods

Four hundred twenty‐three individuals with a history of ≥15 pack‐years smoking had pulmonary function measurements conducted. A second‐order input–output model was used to describe the dynamics of the forced expiration. The capability of the model parameters to predict presence of disease was explored with a support vector machine classifier. In the discordant individuals, newly classified subjects were validated by other pulmonary function tests.

Results

In the non‐discordant subjects (n = 370), the second‐order model was able to confirm a diagnosis of COPD in 95% of subjects (n = 351). In the discordant individuals (n = 53), the classification by dynamic flow analysis found 28 patients to be healthy whereas 25 patients were still classified as COPD. Hyperinflation, increased airways resistance and reduced dynamic volumes were observed in the newly identified COPD group of discordant subjects. When using non‐spirometry‐based pulmonary function criteria as a standard for correct diagnoses in the individual discordant subjects, the model allocated 68% (n = 36) of the discordant to a correct diagnosis.

Conclusions

Expiratory flow dynamics can detect airflow limitation and indicate the presence of COPD. In discordant subjects, our methodology allows a better identification of subjects with or without characteristics of COPD.
Cyst‐based measurements for assessing lymphangioleiomyomatosis in computed tomography
Authors: Lo P. , Brown M. S. , Kim H. , Kim H. , Argula R. , Strange C. , Goldin J. G.
Published: April 2015

Purpose:

To investigate the efficacy of a new family of measurements made on individual pulmonary cysts extracted from computed tomography (CT) for assessing the severity of lymphangioleiomyomatosis (LAM).

Methods:

CT images were analyzed using thresholding to identify a cystic region of interest from chest CT of LAM patients. Individual cysts were then extracted from the cystic region by the watershed algorithm, which separates individual cysts based on subtle edges within the cystic regions. A family of measurements were then computed, which quantify the amount, distribution, and boundary appearance of the cysts. Sequential floating feature selection was used to select a small subset of features for quantification of the severity of LAM. Adjusted R2 from multiple linear regression and R2 from linear regression against measurements from spirometry were used to compare the performance of our proposed measurements with currently used density based CT measurements in the literature, namely, the relative area measure and the D measure.

Results:

Volumetric CT data, performed at total lung capacity and residual volume, from a total of 49 subjects enrolled in the MILES trial were used in our study. Our proposed measures had adjusted R2 ranging from 0.42 to 0.59 when regressing against the spirometry measures, with p < 0.05. For previously used density based CT measurements in the literature, the best R2 was 0.46 (for only one instance), with the majority being lower than 0.3 or p > 0.05.

Conclusions:

The proposed family of CT‐based cyst measurements have better correlation with spirometric measures than previously used density based CT measurements. They show potential as a sensitive tool for quantitatively assessing the severity of LAM.
The performance of normal‐tissue complication probability models in the presence of confounding factors
Authors: Onjukka Eva , Baker Colin , Nahum Alan
Published: April 2015

Purpose:

This work explores different methods for accounting for patient‐specific factors in normal‐tissue complication probability (NTCP) modeling, and compares the performance of models using pseudoclinical datasets for “lung” and “rectum” complications.

Methods:

Datasets consisting of dose distributions and resulting normal‐tissue complications were simulated, letting varying levels of confounding factors (i.e., nondosimetric factors) influence the outcome. The simulated confounding factors were patient radiosensitivity and health status. Seven empirical NTCP models were fitted to each dataset; this is analogous to fitting alternative models to datasets from different populations, treated with the same technique. The performance of these models was compared using the area under the ROC curve (AUC) and the impact of confounding factors on the model performance was studied. The patient‐specific factors were then accounted for by (1) stratification and (2) two ways of modifying the traditional NTCP models to include these factors.

Results:

Confounding factors had a greater impact on model performance than the choice of model. All models performed similarly well on the rectum datasets (except the maximum dose model), while critical‐volume type models were slightly better than the mean dose‐, the Lyman–Kutcher–Burman‐, and the relative seriality models for lung. This difference was more apparent without confounding factors in the dataset. The two alternative functions including patient‐specific factors used in this work (one logistic and one cumulative normal function) were found to be equivalent, and more efficient than stratifying datasets according to patient‐specific factors and fitting models to subgroups individually. For datasets including confounding factors, the performance improved greatly when using models accounting for these; AUC increased from around 0.7 to close to unity.

Conclusions:

This work shows that identifying confounding factors, and developing methods to quantify them, is more important than the choice of NTCP model. Most dose–volume histogram (DVH)‐based NTCP models can be generalized to include confounding factors.
Estimating the viscosity of a highly viscous liquid droplet through the relaxation time of a dry spot
Authors: Sellier M. , Grayson J. W. , Renbaum-Wolff L. , Song M. , Bertram A. K.
Published: April 2015

We discuss in this paper a technique which enables the estimation of the viscosity of microscopic droplets, with application to particles suspended in the atmosphere. The principle of this technique is to deposit a droplet of material approximately 30–100 μm in diameter on a substrate and poke it with a sharp needle hence generating a hole. The amount of sample needed to perform such measurement allows the viscosity of small sample volumes (less than a microliter), such as those generated from atmospheric sampling, to be determined. We show here that the time required for the droplet to relax to its equilibrium shape can be related to the viscosity. We hereby present two mathematical models based on the lubrication approximation which are able to capture the droplet relaxation dynamics. One model is fully transient and resolves the dynamics of the wetting front using a disjoining pressure approach. The other is quasistatic and requires a relationship between the contact line velocity and the contact angle. Comparing the computed relaxation time to that measured experimentally enables the approximate evaluation of the viscosity. The mathematical models are first tested against data from the literature for the closure of a hole in a continuous thin film and then demonstrated for droplets of the polybutene oil N450000 (trade name Cannon Standard Oil), a high-viscosity standard, which serve as a benchmark sample since it is precisely characterized. We also present here viscosity estimates for droplets consisting of secondary organic material and water which are present over forested region yet remain very poorly understood for a lack of adequate characterization technique.
Dating the Moon-forming impact event with asteroidal meteorites
Authors: Bottke W. F. , Vokrouhlický D. , Marchi S. , Swindle T. , Scott E. R. D. , Weirich J. R. , Levison H.
Published: April 2015

Traces of collisions within collisions

The Moon is widely accepted to have been created by the collision of a Mars-sized body with Earth. However, information about exactly when this event occurred is still welcome. To find out more, Bottke
et al.
compared models and the meteorite record with estimates of impact heating. When ejecta was thrown off during the main collision, high-velocity kilometer-sized fragments hit and heated main-belt asteroids. Evidence of such collisions emerges when pieces of those asteroids turn up as meteorites on Earth. The model and empirical record converge on 4.48 billion years ago, confirming previous estimates reached by different approaches.

Science
, this issue p.
321
Anthropogenic environmental changes affect ecosystem stability via biodiversity
Authors: Hautier Yann , Tilman David , Isbell Forest , Seabloom Eric W. , Borer Elizabeth T. , Reich Peter B.
Published: April 2015

Biodiversity protects grassland stability

How biodiversity interacts with ecosystem stability and productivity is key to understanding the impacts of environmental changes on ecosystem functions. In a series of decade-long experiments in temperate grassland, Hautier
et al.
manipulated nitrogen, water, carbon dioxide, herbivory, and fire. In all cases, plant species diversity was important for preserving ecosystem function during environmental change. Hence, the preservation and restoration of biodiversity buffer ecosystems against anthropogenic assault.

Science
, this issue p.
336
Identification and isolation of a dermal lineage with intrinsic fibrogenic potential
Authors: Rinkevich Yuval , Walmsley Graham G. , Hu Michael S. , Maan Zeshaan N. , Newman Aaron M. , Drukker Micha , Januszyk Michael , Krampitz Geoffrey W. , Gurtner Geoffrey C. , Lorenz H. Peter , Weissman Irving L. , Longaker Michael T.
Published: April 2015

Fibroblasts in fibrosis

Excess fibrous connective tissue, similar to scarring, forms during the repair of injuries. Fibroblasts are known to be involved, but their role is poorly characterized. Rinkevich
et al.
identify two lineages of dermal fibroblasts in the dorsal skin of mice (see the Perspective by Sennett and Rendl). A fibrogenic lineage, defined by embryonic expression of
Engrailed-1
, plays a central role in dermal development, wound healing, radiation-induced fibrosis, and cancer stroma formation. Targeted inhibition of this lineage results in reduced melanoma growth and scar formation, with no effect on the structural integrity of the healed skin, thus indicating therapeutic approaches for treating fibrotic disease.

Science
, this issue
10.1126/science.aaa2151
; see also p.
284
Response to Comment on “Local reorganization of xanthophores fine-tunes and colors the striped pattern of zebrafish”
Authors: Singh Ajeet Pratap , Frohnhöfer Hans-Georg , Irion Uwe , Nüsslein-Volhard Christiane
Published: April 2015

Watanabe and Kondo question our conclusion that the current Turing-type model of color patterning in zebrafish requires modification. In addition to xanthophores and melanophores, iridophores are essential for stripe formation in the body, although not in the fins. A model of predictive value should accommodate the in vivo dynamics and interactions of all three chromatophore types in body stripe formation.
Population Structure of Klebsiella pneumoniae Causing Bloodstream Infections at a New York City Tertiary Care Hospital: Diversification of Multidrug-Resistant Isolates
Authors: Gomez-Simmonds Angela , Greenman Michelle , Sullivan Sean B. , Tanner Joshua P. , Sowash Madeleine G. , Whittier Susan , Uhlemann Anne-Catrin
Published: April 2015

Despite the growing importance of carbapenem-resistant
Klebsiella pneumoniae
(CRKP), the clonal relationships between CRKP and antibiotic-susceptible isolates remain unclear. We compared the genetic diversity and clinical features of CRKP, third-generation and/or fourth-generation cephalosporin-resistant (Ceph-R)
K. pneumoniae
, and susceptible
K. pneumoniae
isolates causing bloodstream infections at a tertiary care hospital in New York City between January 2012 and July 2013. Drug susceptibilities were determined with the Vitek 2 system. Isolates underwent multilocus sequence typing and PCR sequencing of the
wzi
and
bla
KPC
genes. Clinical and microbiological data were extracted from patient records and correlated with molecular data. Among 223 patients, we identified 272 isolates. Of these, 194 were susceptible, 30 Ceph-R, and 48 CRKP, belonging to 144 sequence types (STs). Susceptible (127 STs) and Ceph-R (20 STs) isolates were highly diverse. ST258 dominated CRKP strains (12 STs, with 63% ST258). There was minimal overlap in STs between resistance groups. The
bla
KPC-3
gene (30%) was restricted to ST258/
wzi
154, whereas
bla
KPC-2
(70%) was observed for several
wzi
allele types. CRKP infections occurred more frequently among solid organ transplant (31%) and dialysis (17%) patients. Mortality rates were high overall (28%) and highest among CRKP-infected patients (59%). In multivariable analyses, advanced age, comorbidities, and disease severity were significant predictors of 30-day mortality rates, whereas the
K. pneumoniae
susceptibility phenotype was not. Among CRKP infections, we observed a borderline significant association of increased mortality rates with ST258 and the
wzi
154 allele. Although the clonal spread of ST258 continues to contribute substantially to the dissemination of CRKP, non-ST258 strains appear to be evolving. Further investigations into the mechanisms promoting CRKP diversification and the effects of clonal backgrounds on outcomes are warranted.
Herpes Simplex Virus 1 US3 Phosphorylates Cellular KIF3A To Downregulate CD1d Expression
Authors: Xiong Ran , Rao Ping , Kim Seil , Li Michelle , Wen Xiangshu , Yuan Weiming
Published: April 2015

Herpes simplex virus 1 (HSV-1) causes one of the most prevalent herpesviral infections in humans and is the leading etiological agent of viral encephalitis and eye infections. Our understanding of how HSV-1 interacts with the host at the cellular and organismal levels is still limited. We and others previously reported that, upon infection, HSV-1 rapidly and efficiently downregulates CD1d cell surface expression and suppresses the function of NKT cells, a group of innate T cells with critical immunoregulatory function. The viral protein kinase US3 plays a major role in this immune evasion mechanism, and its kinase activity is required for this function. In this study, we investigated the cellular substrate(s) phosphorylated by US3 and how it mediates US3 suppression of CD1d recycling. We identified the type II kinesin motor protein KIF3A as a critical kinesin factor in the cell surface expression of CD1d. Interestingly, KIF3A is phosphorylated by US3 both
in vitro
and in infected cells. Mass spectrometry analysis of purified KIF3A showed that it is phosphorylated predominantly at serine 687 by US3. Ablation of this phosphorylation abolished US3-mediated downregulation of CD1d expression, suggesting that phosphorylation of KIF3A is the primary mechanism of HSV-1 suppression of CD1d expression by US3 protein. Understanding of the precise mechanism of viral modulation of CD1d expression will help to develop more efficient vaccines in the future to boost host NKT cell-mediated immune responses against herpesviruses.

IMPORTANCE
Herpes simplex virus 1 (HSV-1) is among the most common human pathogens. Little is known regarding the exact mechanism by which this virus evades the human immune system, particularly the innate immune system. We previously reported that HSV-1 employs its protein kinase US3 to modulate the expression of the key antigen-presenting molecule CD1d to evade the antiviral function of NKT cells. Here we identified the key cellular motor protein KIF3A as a cellular substrate phosphorylated by US3, and this phosphorylation event mediates US3-induced immune evasion.
Timing Is Everything: Coordinated Control of Host Shutoff by Influenza A Virus NS1 and PA-X Proteins
Authors: Khaperskyy Denys A. , McCormick Craig
Published: April 2015

Like all viruses, influenza viruses (IAVs) use host translation machinery to decode viral mRNAs. IAVs ensure efficient translation of viral mRNAs through host shutoff, a process whereby viral proteins limit the accumulation of host proteins through subversion of their biogenesis. Despite its small genome, the virus deploys multiple host shutoff mechanisms at different stages of infection, thereby ensuring successful replication while limiting the communication of host antiviral responses. In this Gem, we review recent data on IAV host shutoff proteins, frame the outstanding questions in the field, and propose a temporally coordinated model of IAV host shutoff.
Dynasore Disrupts Trafficking of Herpes Simplex Virus Proteins
Authors: Mues Mascha B. , Cheshenko Natalia , Wilson Duncan W. , Gunther-Cummins Leslie , Herold Betsy C.
Published: April 2015

Dynasore, a small-molecule inhibitor of the GTPase activity of dynamin, inhibits the entry of several viruses, including herpes simplex virus (HSV), but its impact on other steps in the viral life cycle has not been delineated. The current study was designed to test the hypothesis that dynamin is required for viral protein trafficking and thus has pleiotropic inhibitory effects on HSV infection. Dynasore inhibited HSV-1 and HSV-2 infection of human epithelial and neuronal cells, including primary genital tract cells and human fetal neurons and astrocytes. Similar results were obtained when cells were transfected with a plasmid expressing dominant negative dynamin. Kinetic studies demonstrated that dynasore reduced the number of viral capsids reaching the nuclear pore if added at the time of viral entry and that, when added as late as 8 h postentry, dynasore blocked the transport of newly synthesized viral proteins from the nucleus to the cytosol. Proximity ligation assays demonstrated that treatment with dynasore prevented the colocalization of VP5 and dynamin. This resulted in a reduction in the number of viral capsids isolated from sucrose gradients. Fewer capsids were observed by electron microscopy in dynasore-treated cells than in control-treated cells. There were also reductions in infectious progeny released into culture supernatants and in cell-to-cell spread. Together, these findings suggest that targeting dynamin-HSV interactions may provide a new strategy for HSV treatment and prevention.

IMPORTANCE
HSV infections remain a global health problem associated with significant morbidity, particularly in neonates and immunocompromised hosts, highlighting the need for novel approaches to treatment and prevention. The current studies indicate that dynamin plays a role in multiple steps in the viral life cycle and provides a new target for antiviral therapy. Dynasore, a small-molecule inhibitor of dynamin, has pleiotropic effects on HSV-1 and HSV-2 infection and impedes viral entry, trafficking of viral proteins, and capsid formation.
Penile and generalised calciphylaxis in peritoneal dialysis
Authors: Sarkis Edmond
Published: April 2015

This is a rare case of penile and generalised calciphylaxis. We describe the case of a patient admitted to our hospital for septic shock and necrotic skin findings, end-stage renal disease on peritoneal dialysis. Skin findings turned out to be calciphyactic lesions. The patient was taken to the operating room for penile debridement and started on antibiotics. He was treated with sodium thiosulfate and switched to haemodialysis. Calciphylaxis is a rare disease in which the treatment is basically supportive. Further studies are needed to identify the risk factors, mechanisms of disease and treatment modalities.
American-Indian diabetes mortality in the Great Plains Region 2002–2010
Authors: Kelley Allyson , Giroux Jennifer , Schulz Mark , Aronson Bob , Wallace Debra , Bell Ronny , Morrison Sharon
Published: April 2015

Objective

To compare American-Indian and Caucasian mortality rates from diabetes among tribal Contract Health Service Delivery Areas (CHSDAs) in the Great Plains Region (GPR) and describe the disparities observed.

Research design and methods

Mortality data from the National Center for Vital Statistics and Seer*STAT were used to identify diabetes as the underlying cause of death for each decedent in the GPR from 2002 to 2010. Mortality data were abstracted and aggregated for American-Indians and Caucasians for 25 reservation CHSDAs in the GPR. Rate ratios (RR) with 95% CIs were used and SEER*Stat V.8.0.4 software calculated age-adjusted diabetes mortality rates.

Results

Age-adjusted mortality rates for American-Indians were significantly higher than those for Caucasians during the 8-year period. In the GPR, American-Indians were 3.44 times more likely to die from diabetes than Caucasians. South Dakota had the highest RR (5.47 times that of Caucasians), and Iowa had the lowest RR, (1.1). Reservation CHSDA RR ranged from 1.78 to 10.25.

Conclusions

American-Indians in the GPR have higher diabetes mortality rates than Caucasians in the GPR. Mortality rates among American-Indians persist despite special programs and initiatives aimed at reducing diabetes in these populations. Effective and immediate efforts are needed to address premature diabetes mortality among American-Indians in the GPR.
Urine lipoarabinomannan to monitor antituberculosis therapy response and predict mortality in an HIV-endemic region: a prospective cohort study
Authors: Drain Paul K , Gounder Lilishia , Grobler Anneke , Sahid Faieza , Bassett Ingrid V , Moosa Mahomed-Yunus S
Published: April 2015

Objective

To determine if urinary lipoarabinomannan (LAM) may serve as a biomarker to monitor antituberculosis (TB) therapy response, and whether LAM results before and after treatment are predictive of patient outcomes.

Design

Prospective cohort.

Setting

Outpatient referral clinic and tertiary hospital in South Africa.

Participants

Adults (≥18 years) with ≥2 TB-related symptoms (cough, fever, weight loss, night sweats) for ≥2 weeks being initiated on anti-TB therapy.

Interventions

On enrolment, we obtained urine and nebulised sputum specimens, offered HIV testing and started participants on anti-TB therapy for ≥6 months. We collected urine samples after the 2-month intensive treatment phase and at the completion of anti-TB therapy. Positive LAM results were graded from 1 (low) to 5 (high). Participants were followed for >3 years.

Outcome measures

The primary outcome was change in urine LAM results during anti-TB therapy. The secondary outcome was all-cause mortality.

Results

Among 90 participants, 57 (63%) had culture-confirmed pulmonary TB. Among the 88 participants tested, 82 (93%) were HIV-infected with median CD4 168/mm3(IQR 89–256/mm3). During anti-TB therapy, the percentage of LAM-positive participants decreased from baseline to 2 months (32% to 16%), and from baseline to 6-months (32% to 10%) (p values <0.005). In multivariate longitudinal analyses, urine LAM positivity and grade decreased among those with culture-confirmed pulmonary TB (p<0.0001), and had no change in sputum culture-negative participants. At the 2-month visit, participants with positive laboratory-based LAM or rapid LAM with ≥2+ grade had a significantly greater risk of mortality. In analyses adjusted for age, sex, baseline Karnofsky score and HIV status, participants with a rapid LAM ≥2+ grade after 2 months of anti-TB therapy had a 5.6-fold (95% CI 1.2 to 25.2) greater risk of mortality.

Conclusions

Rapid urine LAM testing may be a valuable tool to monitor anti-TB therapy response and to assess prognosis of patients being treated for pulmonary TB in HIV-endemic regions.