bluuebunny/crossref_metadata_2025 huggingface dataset:
Resourceful Sensemaking: Overcoming Barriers between Marketing and Design in NPD
Authors: Beverland Michael B. , Micheli Pietro , Farrelly Francis J.
Published: February 2016

New product development (NPD) success depends on the capacity of different functions to effectively collaborate. In particular, while recent studies have highlighted the importance of marketing and design working together, research suggests this relationship is often fraught with conflict due to different “thought worlds.” However, empirical research also identifies that the solution lies not in reducing the psychological distance between the two functions, but in the sensemaking practices used by designers and marketers to expand each other's understanding of the potential NPD solution. This process is known as resourceful sensemaking, and it refers to practitioners’ capacity to transform knowledge with the aim of expanding each other's horizons to ensure better team outcomes. Drawing on 71 interviews with designers and marketers in Australia and New Zealand, we examine how each function strategically deploys knowledge of the other to improve NPD outcomes. Building on the sensemaking literature, we demonstrate that while still drawing on different thought worlds, the inputs of both designers and marketers are necessary for effective NPD. We also identify that both are capable of creating a common framework of meaning through three resourceful sensemaking practices: exposing, co‐opting, and repurposing. Moreover, we identify the need for resourceful sensemaking that results in horizon‐expanding discourse among those involved in NPD. These practices are found to enable marketers and designers to expand the range of considerations and inputs into NPD; help organizations reconcile either/or dualisms; and lead them to identify unmet consumer needs, which result in the creation of innovative products. This paper thereby advances understanding of interfunctional coordination in NPD, integration of design into NPD, and sensemaking more broadly.
Percentage of REM sleep is associated with overnight change in leptin
Authors: Olson Christy A. , Hamilton Nancy A. , Somers Virend K.
Published: February 2016

Sleep contributes importantly to energy homeostasis, and may impact hormones regulating appetite, such as leptin, an adipocyte‐derived hormone. There is increasing evidence that sleep duration, and reduced rapid eye movement sleep, are linked to obesity. Leptin has central neural effects beyond modulation of appetite alone. As sleep is not a unifrom process, interactions between leptin and sleep stages including rapid eye movement sleep may play a role in the relationship between sleep and obesity. This study examined the relationship between serum leptin and rapid eye movement sleep in a sample of healthy adults. Participants were 58 healthy adults who underwent polysomnography. Leptin was measured before and after sleep. It was hypothesized that a lower percentage of rapid eye movement sleep would be related to lower leptin levels during sleep. The relationship between percentage of rapid eye movement sleep and leptin was analysed using hierarchical linear regression. An increased percentage of rapid eye movement sleep was related to a greater reduction in leptin during sleep even when controlling for age, gender, percent body fat and total sleep time. A greater percentage of rapid eye movement sleep was accompanied by more marked reductions in leptin. Studies examining the effects of selective rapid eye movement sleep deprivation on leptin levels, and hence on energy homeostasis in humans, are needed.
Sampling effort required to recover the main gradients in marine benthic species composition
Authors: van Son Thijs Christiaan , Halvorsen Rune , Bakke Torgeir
Published: February 2016

Marine benthic surveys and monitoring programs may have several goals. When the aim of such studies is to reveal and describe gradients in species composition, the gain in ecological insight achieved by the study depends on how well the spatial variability of species’ occurrence and abundance within the study area is covered by the sampling design. The common practice in such programs is to collect four or five grab samples from each visited site to capture the site's species composition. The rationale for this practice is based on the aim of capturing a large proportion of species at a specific site (i.e. point). We argue that this practice has been established without taking Iterative approaches into account, such as decreasing the sampling effort at each site and instead increase the number of sites visited. The collection and processing of data from marine sediment ecosystems are time‐consuming and, thus, expensive. Therefore, finding the optimal trade‐off between the number of sites visited and the number of samples per site is important. We examined this trade‐off by exploring how reduction of sampling effort per site affects the stability and recovery of gradients in species composition of marine benthic macrofauna. Our full data set consisted of four grab samples from each of 28 sites from the inner part of the Oslofjord, SE Norway. Procrustes analysis and calculation of Kendall's rank correlation coefficients showed that the main gradient in species composition extracted by detrended correspondence analysis of data sets with reduced per‐site sampling effort closely resembled the main gradient extracted for the full data set. Our results therefore suggest that marine benthic surveys that aim to identify the main gradient structure of species composition and relate this structure to main environmental complex gradients are likely to benefit from reducing the sampling effort at each site and, instead, increasing the number of visited sites. We argue that coverage of both the variation in species composition and the environment in the study area will then be improved. Monitoring programs with other aims than to identify the main gradients in species composition may also benefit from the adoption of a many‐sites, one‐sample sampling strategy. This may be particularly true if additional sampled sites are based on a stratified sampling strategy that ensures that the spatial variability in the study area is accounted for.
Efficiency of calcein tagging on juveniles of the sea urchins Diadema africanum and Paracentrotus lividus
Authors: Rodríguez Adriana , Hernández José Carlos , Clemente Sabrina
Published: February 2016

We evaluated the effectiveness of chemical tagging with the fluorescent marker calcein for two key species of herbivorous sea urchins, Diadema africanum and Paracentrotus lividus, to facilitate medium‐ and long‐term ecological experiments. In total, 98 juveniles of D. africanum and 98 P. lividus were tagged with this fluorescent marker, with 12 combinations of different tagging techniques (chemical bath or injection), concentrations of calcein (2, 10 and 20 mg · l−1), and soaking times (2, 4 and 24 h). Respective control treatments were conducted by means of seawater injection and bathing. The success of tagging was assessed after a month of feeding individuals ad libitum with the algae Dictyota sp. Sea urchins were dissected and their Aristotle's lanterns cleaned with 10% sodium hypochlorite to examine these structures under UV light using a binocular microscope. Each species was evaluated in terms of survival, percentage of tagged individuals and intensity of the resulting tag. The results showed that the method of soaking individuals of both species for 24 h in concentrations of calcein of 10 and 20 mg · l−1 gave the highest percentage survival (100%) and the resulting tags were clearly visible.
Type IV traffic ATPase TrwD as molecular target to inhibit bacterial conjugation
Authors: Ripoll‐Rozada Jorge , García‐Cazorla Yolanda , Getino María , Machón Cristina , Sanabria‐Ríos David , de la Cruz Fernando , Cabezón Elena , Arechaga Ignacio
Published: February 2016

Bacterial conjugation is the main mechanism responsible for the dissemination of antibiotic resistance genes. Hence, the search for specific conjugation inhibitors is paramount in the fight against the spread of these genes. In this pursuit, unsaturated fatty acids have been found to specifically inhibit bacterial conjugation. Despite the growing interest on these compounds, their mode of action and their specific target remain unknown. Here, we identified TrwD, a Type IV secretion traffic ATPase, as the molecular target for fatty acid‐mediated inhibition of conjugation. Moreover, 2‐alkynoic fatty acids, which are also potent inhibitors of bacterial conjugation, are also powerful inhibitors of the ATPase activity of TrwD. Characterization of the kinetic parameters of ATPase inhibition has led us to identify the catalytic mechanism by which fatty acids exert their activity. These results open a new avenue for the rational design of inhibitors of bacterial conjugation in the fight against the dissemination of antibiotic resistance genes.
Acyldepsipeptide antibiotics kill mycobacteria by preventing the physiological functions of the ClpP1P2 protease
Authors: Famulla Kirsten , Sass Peter , Malik Imran , Akopian Tatos , Kandror Olga , Alber Marina , Hinzen Berthold , Ruebsamen‐Schaeff Helga , Kalscheuer Rainer , Goldberg Alfred L. , Brötz‐Oesterhelt Heike
Published: February 2016

The Clp protease complex in Mycobacterium tuberculosis is unusual in its composition, functional importance and activation mechanism. Whilst most bacterial species contain a single ClpP protein that is dispensable for normal growth, mycobacteria have two ClpPs, ClpP1 and ClpP2, which are essential for viability and together form the ClpP1P2 tetradecamer. Acyldepsipeptide antibiotics of the ADEP class inhibit the growth of Gram‐positive firmicutes by activating ClpP and causing unregulated protein degradation. Here we show that, in contrast, mycobacteria are killed by ADEP through inhibition of ClpP function. Although ADEPs can stimulate purified M. tuberculosis ClpP1P2 to degrade larger peptides and unstructured proteins, this effect is weaker than for ClpP from other bacteria and depends on the presence of an additional activating factor (e.g. the dipeptide benzyloxycarbonyl‐leucyl‐leucine in vitro) to form the active ClpP1P2 tetradecamer. The cell division protein FtsZ, which is a particularly sensitive target for ADEP‐activated ClpP in firmicutes, is not degraded in mycobacteria. Depletion of the ClpP1P2 level in a conditional Mycobacterium bovis BCG mutant enhanced killing by ADEP unlike in other bacteria. In summary, ADEPs kill mycobacteria by preventing interaction of ClpP1P2 with the regulatory ATPases, ClpX or ClpC1, thus inhibiting essential ATP‐dependent protein degradation.
Monitoring population‐level responses of marine mammals to human activities
Authors: Fleishman Erica , Costa Daniel P. , Harwood John , Kraus Scott , Moretti David , New Leslie F. , Schick Robert S. , Schwarz Lisa K. , Simmons Samantha E. , Thomas Len , Wells Randall S.
Published: February 2016

We provide guidance for monitoring whether human activities affect the physiology or behavior of marine mammals and, if so, whether those effects may lead to changes in survival and reproduction at the population level. We suggest that four elements be included in designing and implementing such a monitoring program. The first is development of a theory of change: a set of mechanistic hypotheses that outline why a given activity might be expected to have one or more measurable effects on individuals and populations, and ideally the magnitude, timing, and duration of the effects. The second element, definition of biologically meaningful effect sizes, ultimately facilitates the development of a monitoring program that can detect those magnitudes of effect with the desired levels of precision. The third element, selection of response variables for monitoring, allows inference to whether observed changes in the status of individuals or populations are attributable to a given activity. Visual observations, passive acoustic and tagging instruments, and direct physical measurements all can provide data that facilitate quantitative hypothesis testing. The fourth element is specification of the temporal sequence of monitoring. These elements also can be used to inform monitoring of the responses of other taxonomic groups to human activities.
Specificity of mannan antigen and anti‐mannan antibody screening in patients with haematological malignancies at risk for fungal infection
Authors: Duettmann Wiebke , Koidl Christoph , Krause Robert , Lackner Gertrude , Woelfler Albert , Hoenigl Martin
Published: February 2016

Combination of mannan antigen and anti‐mannan antibody (Mn/A‐Mn) testing has been reported a useful and specific strategy for diagnosis of invasive Candida infections (ICIs). We evaluated Mn/A‐Mn as a screening tool in patients with haematological malignancies. This clinical prospective study was performed at the Division of Hematology, Medical University Graz, Austria between July and December 2012. Patients at risk for fungal infection were included into the study and twice weekly screened by Mn/A‐Mn testing, yielding 650 samples. Of overall 67 patients 66 had no evidence for ICI. From those, 153/640 serum samples (23.9%) were positive for mannan Ab, and nine (1.4%) for Ag. Most false positive Ab results were observed among 375 samples from patients without haematopoietic stem cell transplantation (34.9% resulted positive). Combined specificity of Mn/A‐Mn was 74.8%. Of 10 samples obtained in the single patient with candidemia, five were positive for mannan Ag (from the day of diagnosis up to 40 days after detection of candidemia) and none for Ab. In conclusion, mannan Ab screening yielded a high number of false positive results. While mannan Ag was found to be highly specific and may have potential for diagnostic driven testing, mannan Ab testing cannot be recommended based on our study results.
Methionine restriction beyond life‐span extension
Authors: Ables Gene P. , Hens Julie R. , Nichenametla Sailendra N.
Published: February 2016

Dietary methionine restriction (MR) extends life span across species via various intracellular regulatory mechanisms. In rodents, MR induces resistance against adiposity, improves hepatic glucose metabolism, preserves cardiac function, and reduces body size, all of which can affect the onset of age‐related diseases. Recent studies have shown that MR‐affected biomarkers, such as fibroblast growth factor 21, adiponectin, leptin, cystathionine β synthase, and insulin‐like growth factor 1, can potentially alter physiology. The beneficial effects of MR could be explained in part by its ability to reduce mitochondrial oxidative stress. Studies have revealed that MR can reduce reactive oxygen species that damage cells and promote cancer progression. It has been demonstrated that either MR or the targeting of specific genes in the methionine cycle could induce cell apoptosis while decreasing proliferation in several cancer models. The complete mechanism underlying the actions of MR on the cell cycle during cancer has not been fully elucidated. Epigenetic mechanisms, such as methylation and noncoding RNAs, are also possible downstream effectors of MR; future studies should help to elucidate some of these mechanisms. Despite evidence that changes in dietary methionine can affect epigenetics, it remains unknown whether epigenetics is a mechanism in MR. This review summarizes research on MR and its involvement in metabolism, cancer, and epigenetics.
The influence of herbivores on primary producers can vary spatially and interact with disturbance
Authors: Carnell Paul E. , Keough Michael J.
Published: February 2016

Identifying the major drivers of ecosystem change remains a central area of ecological research. Although top–down drivers of change have received particular focus, we still have little understanding of how consistently these factors control an ecosystem's shift in both directions, between different ecosystem states. Using a crossed experiment in a shallow embayment in southeastern Australia, we investigated the roles of disturbance (kelp removal) and sea urchin herbivory (via increased density) to determine their contributions to shifts away from a kelp‐dominated community. In a second experiment, done in urchin barren areas at two sites, we tested whether reductions in ambient sea urchin densities allowed an algal shift in the reverse direction. In both experiments, we observed that high densities of sea urchins could negatively influence kelp and macroalgal abundance. However, in the kelp bed, a moderate or severe disturbance resulted in a comparable algal response, irrespective of urchin density. The influence of sea urchins also varied dramatically between the two urchin barren sites. Here, reducing urchin densities resulted in algal recovery at one site, but at the other site, substantial colonisation of barren areas by canopy‐forming brown algae and Ulvales occurred across all (low, medium, and high) urchin density treatments. Our findings illustrate multiple pathways of urchin barren creation and algal recovery, and reveal that shifts both to and from an urchin barren state can occur irrespective of herbivore pressure. These alternate pathways can operate over short spatial distances or with different regimes of disturbance.
Allergy protection by cowshed bacteria – recent findings and future prospects
Authors: Kauth Marion , Heine Holger
Published: February 2016

Since the first publication in 1999, numerous epidemiologic studies provided strong evidence that frequent contact to a traditional farm environment in early life protects children from the development of allergic airway diseases. These consistent findings prompted enormous efforts to identify and characterize the potential causative factors and the underlying immunologic mechanisms in experimental studies. The cumulating evidence for the role of the cowshed‐associated bacterial flora led to enhanced efforts not only to identify the relevant species but also to examine their specific immunomodulatory capacity, the bacterial components involved, and particularly the cellular and molecular mechanisms of their interaction with the immune system. We review here the methods applied to identify relevant bacterial species, the species which emerged thereof, and the similarities and differences in their mode of action as revealed so far. We further consider the impact of the current knowledge on worthwhile clinical application and reflect on the required next steps to foster the translation of the encouraging scientific progress which has been made in recent years.
Successful Graded Mirror Therapy in a Patient with Chronic Deafferentation Pain in Whom Traditional Mirror Therapy was Ineffective: A Case Report
Authors: Mibu Akira , Nishigami Tomohiko , Tanaka Katsuyoshi , Osumi Michihiro , Tanabe Akihito
Published: February 2016

A 43‐year‐old man had deafferentation pain in his right upper extremity secondary to brachial plexus avulsion from a traffic accident 23 years previously. On our initial examination, he had severe tingling pain with numbness in the right fingers rated 10 on the numerical rating scale. The body perception of the affected third and fourth fingers was distorted in the flexed position. Although he performed traditional mirror therapy (TMT) for 4 weeks in the same methods as seen in previous studies, he could not obtain willed motor imagery and pain‐alleviation effect. Therefore, we modified the task of TMT: Graded mirror therapy (GMT). GMT consisted of five stages: (1) observation of the mirror reflection of the unaffected side without imagining any movements of the affected side; (2) observation of the mirror reflection of the third and fourth fingers changing shape gradually adjusted from a flexed position to a extended position; (3) observation of the mirror reflection of passive movement; (4) motor imagery of affected fingers with observation of the mirror reflection (similar to TMT); (5) motor imagery of affected fingers without mirror. Each task was performed for 3 to 4 weeks. As a result, pain intensity during mirror therapy gradually decreased and finally disappeared. The body perception of the affected fingers also improved, and he could imagine the movement of the fingers with or without mirror. We suggested that GMT starting from the observation task without motor imagery may effectively decrease deafferentation pain compared to TMT.
Effect of Perioperative Intravenous Lidocaine Infusion on Acute and Chronic Pain after Breast Surgery: A Meta‐Analysis of Randomized Controlled Trials
Authors: Chang Yuan‐Ching , Liu Chien‐Liang , Liu Tsang‐Pai , Yang Po‐Sheng , Chen Ming‐Jen , Cheng Shih‐Ping
Published: February 2016

Objectives

Intravenous lidocaine infusion has been shown to reduce postoperative pain among patients undergoing abdominal surgery. This study aimed to evaluate the effects of perioperative lidocaine administration in breast surgery.

Methods

A meta‐analysis of randomized controlled trials comparing lidocaine infusion vs. placebo/routine treatment was performed. Standardized mean difference (SMD) or risk ratio (RR) with 95% confidence intervals (CIs) was calculated from pooled data. Random‐effects models were used, and heterogeneity was assessed.

Results

A total of 4 reports (3 primary studies and 1 extension) with 84 patients randomized to the lidocaine group and 83 patients randomized to the control group were included. There was no difference in pain scores at rest or during activity between the 2 groups from postoperative 2 hours to 3 days. At postoperative 72 hours, the lidocaine group had fewer analgesics consumed (SMD, −0.479; 95% CI, −0.914 to −0.043; P = 0.031). Chronic pain was assessed 3 to 6 months after breast surgery in 51 patients of the lidocaine group and 46 patients of the control group. Patients in the lidocaine group had significantly lower risk for the development of chronic pain (RR, 0.332; 95% CI, 0.141 to 0.781; P = 0.012).

Conclusion

The results indicate no significant benefits of intravenous lidocaine infusion in terms of acute postoperative pain. Although lidocaine seems to attenuate the risk of chronic pain after breast surgery, there is insufficient evidence to conclude that lidocaine infusion is of proved benefit because the results were based on a limited number of small trials.
New Insight into the Water‐Soluble Chlorophyll‐Binding Protein from Lepidium virginicum
Authors: Kell Adam , Bednarczyk Dominika , Acharya Khem , Chen Jinhai , Noy Dror , Jankowiak Ryszard
Published: February 2016

This study describes new recombinant water‐soluble chlorophyll (Chl)‐binding proteins (WSCP) from Lepidium virginicum (LvWSCP). This complex binds four Chls (i.e. two dimers of Chls) per protein tetramer. We show that absorption, emission, hole‐burned (HB) spectra and the shape of the zero‐phonon hole (ZPH) action spectrum are consistent with the presence of uncorrelated excitation energy transfer between two Chl dimers. Thus, there is no need to include slow protein relaxation within the lowest excited state (as suggested in a previous analysis of cauliflower WSCP [Schmitt, F.‐J. et al. (2008) J. Phys. Chem. B, 112, 13951; Pieper, J. et al. (2011) J. Phys. Chem. B, 115, 4053]) in order to explain the large shift observed between the maxima of the ZPH action and emission spectra. Experimental evidence is provided which shows that electron exchange between lowest energy Chls and the protein may occur, i.e. electrons can be trapped at low temperature by nearby aromatic amino acids. The latter explains the shape of nonresonant HB spectra (i.e. the absence of antihole), demonstrating that the hole‐burning process in LvWSCP is largely photochemical in nature, though a small contribution from nonphotochemical hole burning (in resonant holes) is also observed.
A Regional Decision Support Scheme for Pest Risk Analysis in Southeast Asia
Authors: Soliman T. , MacLeod A. , Mumford J. D. , Nghiem T. P. L. , Tan H. T. W. , Papworth S. K. , Corlett R. T. , Carrasco L. R.
Published: February 2016

A key justification to support plant health regulations is the ability of quarantine services to conduct pest risk analyses (PRA). Despite the supranational nature of biological invasions and the close proximity and connectivity of Southeast Asian countries, PRAs are conducted at the national level. Furthermore, some countries have limited experience in the development of PRAs, which may result in inadequate phytosanitary responses that put their plant resources at risk to pests vectored via international trade. We review existing decision support schemes for PRAs and, following international standards for phytosanitary measures, propose new methods that adapt existing practices to suit the unique characteristics of Southeast Asia. Using a formal written expert elicitation survey, a panel of regional scientific experts was asked to identify and rate unique traits of Southeast Asia with respect to PRA. Subsequently, an expert elicitation workshop with plant protection officials was conducted to verify the potential applicability of the developed methods. Rich biodiversity, shortage of trained personnel, social vulnerability, tropical climate, agriculture‐dependent economies, high rates of land‐use change, and difficulties in implementing risk management options were identified as challenging Southeast Asian traits. The developed methods emphasize local Southeast Asian conditions and could help support authorities responsible for carrying out PRAs within the region. These methods could also facilitate the creation of other PRA schemes in low‐ and middle‐income tropical countries.
A General Framework for Updating Belief Distributions
Authors: Bissiri P. G. , Holmes C. C. , Walker S. G.
Published: February 2016

We propose a framework for general Bayesian inference. We argue that a valid update of a prior belief distribution to a posterior can be made for parameters which are connected to observations through a loss function rather than the traditional likelihood function, which is recovered as a special case. Modern application areas make it increasingly challenging for Bayesians to attempt to model the true data-generating mechanism. For instance, when the object of interest is low dimensional, such as a mean or median, it is cumbersome to have to achieve this via a complete model for the whole data distribution. More importantly, there are settings where the parameter of interest does not directly index a family of density functions and thus the Bayesian approach to learning about such parameters is currently regarded as problematic. Our framework uses loss functions to connect information in the data to functionals of interest. The updating of beliefs then follows from a decision theoretic approach involving cumulative loss functions. Importantly, the procedure coincides with Bayesian updating when a true likelihood is known yet provides coherent subjective inference in much more general settings. Connections to other inference frameworks are highlighted.
Walking down ‘Via Dolorosa’ from primary health care to the specialty pain clinic – patient and professional perceptions of inequity in rehabilitation of chronic pain
Authors: Lehti Arja , Fjellman‐Wiklund Anncristine , Stålnacke Britt‐Marie , Hammarström Anne , Wiklund Maria
Published: February 2016

Objective

To analyse patient and professional perceptions about (in)equity of care and rehabilitation of chronic pain patients from primary health care to assessment at a specialty rehabilitation clinic.

Setting and methods

This qualitative study consists one focus group interview with eight general practitioners who refer patients to pain rehabilitation clinics, 10 individual interviews with patients who were assessed at a pain rehabilitation clinic and seven interviews with professionals participating in multimodal assessment teams at a pain rehabilitation clinic. Interview analysis was conducted by the grounded theory method.

Results

The core category Via Dolorosa, the way of suffering and pain, captured how gender and sociocultural context may contribute to advantages and disadvantages during patient journeys from primary health care to a pain rehabilitation clinic. Patients and professionals perceived pain as a low‐ranking illness, and women and men used different gendered strategies to legitimise the pain and to be taken seriously. Being ‘a proper patient ready to change’ and having ‘likeness’ between patients and professionals were viewed as advantageous in rehabilitation of pain patients. Patients with higher educational levels were perceived as easier to interact with and had better access to health care. Professional thoughts about gender norms influenced the rehabilitation options. The rehabilitation programme was seen by several professionals to be better suited for women than men, which could lead to unequal care.

Conclusion

From an equity and gender perspective, our study highlights the complexity in rehabilitation of chronic pain patients – both from patient and professional perspectives. Awareness of gendered and the biased preconceptions and norms is crucial when professionals struggle to offer equitable health care and rehabilitation.
A novel allele, HLA‐B*55:70 was identified in a Chinese cord blood donor
Authors: Wang W. , Chen N.‐Y. , Dong L.‐N. , He J. , Zhu F.‐M.
Published: February 2016

HLA‐B*55:70 has one base substitution at position 199 C>T in exon 2 compared to HLA‐B*55:02:01.
Significances of red cell bound immunoglobulin G as detected by flow cytometry in patients with Coombs‐negative immune hemolysis
Authors: Thedsawad A. , Taka O. , Wanachiwanawin W.
Published: February 2016

Objectives

This study was to investigate the use of flow cytometry for detection and quantitation of red blood cells (RBC) bound IgG in immune hemolysis of patients with autoimmune hemolytic anaemia (AIHA) and systematic lupus erythematosus (SLE).

Background

Two to ten percent of patients with warm‐autoimmune hemolytic anaemia (WAIHA) exhibit a negative direct Coombs test. Flow cytometry has been applied to detect RBC bound IgG with high accuracy, reproducibility and sensitivity.

Methods

In this study 45 and 75 patients with AIHA and SLE, respectively were evaluated for RBC bound IgG by direct Coombs test and flow cytometry.

Results

Seventy‐one percent (32/45) and 31% (23/75) of patients with AIHA and SLE respectively, had laboratory evidence of hemolysis. A positive flow cytometry, as defined by mean fluorescent intensity (MFI) values >0·21 and IgG molecules >28, was found in 4 of 32 (12·5%) and 4 of 23 (17·4%) patients with AIHA and SLE who had hemolysis with a negative direct Coombs test. There were very strong and strong correlations between the strength of direct Coombs test with MFI values and IgG molecules in patients with AIHA and SLE, respectively.

Conclusion

Flow cytometry can be applied in the diagnosis of Coombs‐negative hemolytic anaemia in patients with AIHA and SLE.
Bone marrow donor‐related variables associated with harvest outcome inHLA‐haploidentical transplantation with postinfusion cyclophosphamide
Authors: Rimondo A. , Bramanti S. , Crocchiolo R. , Giordano L. , Sarina B. , Morabito L. , Perotti C. , Timofeeva I. , Capizzuto R. , Santoro A. , Castagna L.
Published: February 2016

Background and objectives

Several transplantation outcomes have been shown to be associated with the infused bone marrow cell dose/kg of the recipient's body weight. The donor bone marrow density is directly related to the infused cell dose. The aim of the present study was to identify donor‐related variables that are associated with high donor bone marrow density.

Materials and methods

We retrospectively analysed the predictive factors of high marrow density in 65 consecutiveHLA‐haploidentical bone marrow donors harvested at our centre between 2009 and 2013.

Results

Body mass index (BMI) and peripheral white blood cell (WBC) count were directly associated with bone marrow density (regression coefficientβ= 5·33 andβ= 2·93, respectively;P< 0·01). The likelihood of obtaining a collection with a high density was first predicted usingBMI(BMI≥30, mean density = 25·8TNC/ml × 106). Second, donors with aBMI<30 were split into two groups according to peripheralWBCcount (WBC<8 × 103/mm3: mean density = 18·4TNC/ml × 106;WBC≥8 × 103/mm3: mean density = 23·1TNC/ml × 106). We also observed that the density of the first collected bag directly correlated with the overall density (R2= 0·69,P< 0·01).

Conclusion

The donor‐related featuresBMIandWBCcount affect the cell quantity obtainable with the harvest and should be taken into account when choosing the donor.
The impact of donor characteristics on the immune cell composition of second allografts in Chinese people
Authors: Chen L. , Chang Y‐J. , Xu L‐P. , Huang X‐J.
Published: February 2016

Background

The association of the donor characteristics with the immune cell composition in second allografts remains poorly understood. In this study, we investigated retrospectively the effects of the donor characteristics on the immune cell composition in second allografts.

Study design and methods

The immune cell composition in second allografts of granulocyte colony‐stimulating factor (G‐CSF) mobilized peripheral blood harvests from 100 healthy donors (male, 47, female, 53; median age, 39 years old) who underwent a second‐time donation were correlated with their donor characteristics.

Results

The median counts ofCD3+T cells,CD4+T cells,CD8+T cells,CD3+CD4−CD8−T cells and monocytes in allografts were 150·17 × 106/kg, 82·57 × 106/kg, 48·02 × 106/kg and 24·97 × 106/kg, respectively. Multivariate analysis showed that the number of lymphocytes and platelets pre‐first collection of G‐CSFmobilized blood (FM) was strongly associated with the number of total lymphocytes (for lymphocytes,P= 0·003; for platelets,P= 0·012),CD3+T cells (for lymphocytes,P= 0·009; for platelets,P= 0·004) andCD3+CD4+T cells (for lymphocytes,P= 0·035; for platelets,P= 0·004) in the second allograft. The donor'sBMIwas negatively related to the number ofCD3+T cells (P= 0·022) andCD3+CD4+T cells (P= 0·026) in the second allograft. The donor weight was negatively associated with the number ofCD3+CD4−CD8−T cells (P= 0·015) in the second allograft, while the pre‐FMwhite blood cell count showed a positive correlation (P= 0·009).

Conclusion

The results demonstrate the impact of the donor characteristics, including pre‐FMplatelet count and lymphocyte count, donorBMIand weight, on the immune cell composition in the second allograft.
Prediction of time‐dependent local scour around bridge piers
Authors: Choi Sung‐Uk , Choi Byungwoong
Published: February 2016

Most formulas for predicting the scour depth around bridge piers result in over‐predictions. This is partly due to ignoring the fact that the local scour is a time‐dependent process. Formulas that take into account time‐dependent local scour around bridge piers have been developed in the past. However, these formulas predict the scour process well, but only when applied to datasets from which they were constructed. Motivated by this, the present study proposes a relationship for time‐dependent local scour using dimensional analysis and nonlinear regression. Similarly, another relationship for the time to equilibrium is also developed. The findings indicate that the proposed relationship predicts time‐dependent local scour better than existing formulas. The proposed relationships are applicable to local scour around cylindrical bridge piers. It is assumed that the bed sediment is uniform and the bedform effect is minor and can be ignored.
Positive plant–soil feedbacks of the invasive Impatiens glandulifera and their effects on above‐ground microbial communities
Authors: Pattison Z , Rumble H , Tanner R A , Jin L , Gange A C
Published: February 2016

Impatiens glandulifera is one of the most widespread invasive plant species in the UK. Although aspects of its biology are known, there is little information about its association with microbial communities, both above ground and below ground. Furthermore, it is unknown whether this species exhibits any form of plant–soil feedback (PSF), commonly seen in other invasive weeds. We conducted a PSF experiment, in which plants of I. glandulifera were grown in soil that supported the species and compared with plants grown in a control soil from the same locality. Soil nutrients were measured, and the soil and foliar microbial communities were assessed. Impatiens glandulifera grew larger and faster in conditioned soil compared with the control. Higher levels of phosphate were also found in conditioned soils. Arbuscular mycorrhizal fungal (AMF) colonisation was lower in conditioned soils, suggesting that I. glandulifera may rapidly alter AMF communities in invaded areas. PSFs had a significant effect on the foliar endophyte community, with clear separation of species between conditioned and control soils. These results show that I. glandulifera displayed a positive PSF and the PSF mechanism extended beyond the soil microbial community to affect foliar endophytes. The observed increase in endophytes in plants grown in conditioned soil could enhance resistance to herbivory, thus further accentuating the invasive properties of this species.
Diverse roles for ionotropic glutamate receptors on inhibitory interneurons in developing and adult brain
Authors: Akgül Gülcan , McBain Chris J.
Published: February 2016

Glutamate receptor‐mediated recruitment of GABAergic inhibitory interneurons is a critical determinant of network processing. Early studies observed that many, but not all, interneuron glutamatergic synapses contain AMPA receptors that are GluA2‐subunit lacking and Ca2+ permeable, making them distinct from AMPA receptors at most principal cell synapses. Subsequent studies demonstrated considerable alignment of synaptic AMPA and NMDA receptor subunit composition within specific subtypes of interneurons, suggesting that both receptor expression profiles are developmentally and functionally linked. Indeed glutamate receptor expression profiles are largely predicted by the embryonic origins of cortical interneurons within the medial and caudal ganglionic eminences of the developing telencephalon. Distinct complements of AMPA and NMDA receptors within different interneuron subpopulations contribute to the differential recruitment of functionally divergent interneuron subtypes by common afferent inputs for appropriate feed‐forward and feedback inhibitory drive and network entrainment. In contrast, the lesser‐studied kainate receptors, which are often present at both pre‐ and postsynaptic sites, appear to follow an independent developmental expression profile. Loss of specific ionotropic glutamate receptor (iGluR) subunits during interneuron development has dramatic consequences for both cellular and network function, often precipitating circuit inhibition–excitation imbalances and in some cases lethality. Here we briefly review recent findings highlighting the roles of iGluRs in interneuron development.

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Lysosomal cystine accumulation promotes mitochondrial depolarization and induction of redox‐sensitive genes in human kidney proximal tubular cells
Authors: Sumayao Rodolfo , McEvoy Bernadette , Newsholme Philip , McMorrow Tara
Published: February 2016

Key points

Cystine is a disulphide amino acid that is normally generated in the lysosomes by the breakdown of cystine‐containing proteins.

Previously, we demonstrated that lysosomal cystine accumulation in kidney proximal tubular epithelial cells (PTECs) dramatically reduced glutathione (GSH) levels, which may result in the disruption of cellular redox balance.

In the present study, we show that lysosomal cystine accumulation following CTNS gene silencing in kidney PTECs resulted in elevated intracellular reactive oxygen species production, reduced antioxidant capacity, induction of redox‐sensitive proteins, altered mitochondrial integrity and augmented cell death.

These alterations may represent different facets of a unique cascade leading to tubular dysfunction initiated by lysosomal cystine accumulation and may present a clear disadvantage for cystinotic PTECs in vivo.

Cystine depletion by cysteamine afforded cytoprotection in CTNS knockdown cells by reducing oxidative stress, normalizing intracellular GSH and ATP content, and preserving cell viability.

Cystine is a disulphide amino acid that is normally generated within the lysosomes through lysosomal‐based protein degradation and via extracellular uptake of free cystine. In the autosomal recessive disorder, cystinosis, a defect in the CTNS gene results in excessive lysosomal accumulation of cystine, with early kidney failure a hallmark of the disease. Previously, we demonstrated that silencing of the CTNS gene in kidney proximal tubular epithelial cells (PTECs) resulted in an increase in intracellular cystine concentration coupled with a dramatic reduction in the total GSH content. Because of the crucial role of GSH in maintaining the redox status and viability of kidney PTECs, we assessed the effects of CTNS knockdown‐induced lysosomal cystine accumulation on intracellular reactive oxygen species (ROS) production, activity of classical redox‐sensitive genes, mitochondrial integrity and cell viability. Our results showed that lysosomal cystine accumulation increased ROS production and solicitation to oxidative stress (OS). This was associated with the induction of classical redox‐sensitive proteins, NF‐κB, NRF2, HSP32 and HSP70. Cystine‐loaded PTECs also displayed depolarized mitochondria, reduced ATP content and augmented apoptosis. Treatment of CTNS knockdown PTECs with the cystine‐depleting agent cysteamine resulted in the normalization of OS index, increased GSH and ATP content, and preservation of cell viability. Taken together, the alterations observed in cystinotic cells may represent different facets of a cascade leading to tubular dysfunction and, in combination with cysteamine therapy, may offer a novel link for the attenuation of renal injury and preservation of functions of other organs affected in cystinosis.
Mitigating the Stress Corrosion Cracking of Zircaloy-4 Fuel Sheathing: Siloxane Coatings Revisited
Authors: Ferrier Graham A. , Farahani Mohsen , Metzler Joseph , Chan Paul K. , Corcoran Emily C.
Published: February 2016

For more than 50 years, a thin (3–20 μm) graphite coating has played an important role in limiting the stress corrosion cracking (SCC) of Zircaloy-4 fuel sheathing in CANDU® nuclear reactors. Siloxane coatings, which were examined alongside graphite coatings in the early 1970s, demonstrated even better tolerance against power-ramp-induced SCC and exhibited better wear resistance than graphite coatings. Although siloxane technology developed significantly in the 1980s/1990s, siloxane coatings remain unused in CANDU reactors, because graphite is relatively inexpensive and performs well in-service. However, advanced CANDU designs will accommodate average burnups, exceeding the threshold tolerable by the graphite coating (450  MWh/kgHE). In addition, siloxane coatings may find applicability in pressurized and boiling water reactors, wherein the burnups are inherently larger than those in CANDU reactors. Consequently, a commercially available siloxane coating is evaluated by its present-day chemistry, wear resistance, and performance in hot, stressful, and corrosive environments. After subjecting slotted Zircaloy-4 rings to iodine concentrations exceeding the estimated in-reactor concentration (1  mg/cm3), mechanical deflection tests and scanning electron microscopy (SEM) show that the siloxane coating outperforms the graphite coating in preserving the mechanical integrity of the rings. Furthermore, the baked siloxane coating survived a 50-day exposure to thermal neutron flux ((2.5±0.1)×1011  n/cm2 s) in the SLOWPOKE-2 nuclear reactor at the Royal Military College of Canada.
Iodine Benchmarks in the SARNET Network of Excellence
Authors: Haste Tim , Di Giuli Mirco , Weber Gunter , Weber Sebastian
Published: February 2016

Accurate calculation of iodine behavior in the containment is very important in determining the potential radioactive release to the environment in light water reactor severe accidents (SAs). Of particular significance is the behavior of gas phase iodine, particularly organic iodine, which is difficult to remove by filtration, e.g., in containment venting systems. Iodine behavior is closely linked with the containment thermal hydraulics, which have a major influence on the distribution of iodine throughout the containment atmosphere and sump. In the European 7th Framework SARNET project, European Commission (EC) cofunded from 2007 to 2013, SA modeling code capability was assessed through two integral benchmarks. In the first, the basis was the German THAI Iod-11/12 tests, where molecular iodine transport with atmospheric flows and iodine interactions with steel surfaces were emphasized. In the second, data from the international Phébus FPT3 test were used, where all aspects of SAs were studied from core degradation, fission product (FP) release, circuit transport/deposition, and containment behavior using realistic FP sources. Thermal hydraulics in the containment were simpler, being well-mixed, and radiolytic interactions of iodine, e.g., with painted surfaces, were studied. These interactions may be an important source of organic iodine in the containment atmosphere. The two benchmarks are thus complementary. In the FPT3 exercise, the calculations could predict the containment thermal hydraulic conditions fairly well. For the more detailed data from THAI, differences were noted for atmospheric flows and relative humidities, outside experimental uncertainties, affecting iodine behavior. The FPT3 iodine results themselves showed a spread in calculated results outside data uncertainties, indicating the need for model improvements in this area, e.g., for radiolytic interaction of iodine with paint. Experimental programs to generate the necessary data needed for code improvement have been recently completed, e.g., in the OECD/THAI, THAI2, BIP, and BIP2 projects, or are in progress, in OECD/STEM and EC/PASSAM. When model improvements have been made, repeat benchmarks are planned to check progress toward code convergence with experimental data, e.g., under the aegis of the new NUGENIA association of which SARNET now forms a part.
Geoacoustic inversion in shallow tropical waters for a silty and sandy seabed
Authors: M. C. Sanjana , G. Latha , Potty G. R.
Published: February 2016

Seabed parameters are inverted from ambient noise measurements at two shallow tropical environments with dissimilar seabed characteristics, a silty and a sandy seabed, using an approach that matches the measured and modeled complex vertical coherence. Coherence is modeled using the Green's function output from the model oases, along with theoretical formulation, for a range independent environment. Genetic algorithm is used to search the model parameter space consisting of sound speed, density, and attenuation in the sediment layers and half-space. Reasonable estimates have been obtained for the silty site, whereas the sandy site gave relatively poor parameter estimates due to reflective seabed and shipping interference.