bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical utility of next‐generation sequencing in the diagnosis of hereditary haemolytic anaemias
Authors: Agarwal Archana M. , Nussenzveig Roberto H. , Reading Noel S. , Patel Jay L. , Sangle Nikhil , Salama Mohamed E. , Prchal Josef T. , Perkins Sherrie L , Yaish Hassan M. , Christensen Robert D.
Published: June 2016

Hereditary haemolytic anaemias are genetically and phenotypically heterogeneous disorders characterized by increased red cell destruction, with consequences ranging from innocuous to severe life‐threatening anaemia. Diagnostic laboratories endeavour to assist clinicians reach the exact patient diagnosis by using tests principally based on morphological and biochemical techniques. However, these routine studies may be inconclusive, particularly in newborn infants and when transfusions have recently been administered. Large numbers and size of the potentially involved genes also impose a practical challenge for molecular diagnosis using routine sequencing approaches. To overcome these diagnostic shortcomings, we have utilized next‐generation sequencing to provide a high‐throughput, highly sensitive assay. We developed a panel interrogating 28 genes encoding cytoskeletal proteins and enzymes with sequencing coverage of the coding regions, splice site junctions, deep intronic and regulatory regions. We then evaluated 19 samples, including infants with unexplained extreme hyperbilirubinaemia and patients with transfusion‐dependent haemolytic anaemia. Where possible, inheritance patterns of pathogenic mutations were determined by sequencing of immediate relatives. We conclude that this next‐generation sequencing panel could be a cost‐effective approach to molecular diagnosis of hereditary haemolytic anaemia, especially when the family history is uninformative or when routine laboratory testing fails to identify the causative haemolytic process.
VLA‐4 blockade by natalizumab inhibits sickle reticulocyte and leucocyte adhesion during simulated blood flow
Authors: White Jennell , Krishnamoorthy Sriram , Gupta Dipti , Lancelot Moira , Moore Nancy , Sarnaik Sharada , Hobbs William E. , Light David R. , Hines Patrick
Published: June 2016

Very Late Antigen‐4 (VLA‐4, α4β1‐integrin, ITGA4) orchestrates cell‐cell and cell‐endothelium adhesion. Given the proposed role of VLA‐4 in sickle cell disease (SCD) pathophysiology, we evaluated the ability of the VLA‐4 blocking antibody natalizumab to inhibit SCD blood cell adhesion. Natalizumab recognized surface VLA‐4 on leucocytes and reticulocytes in whole blood from SCD subjects. SCD reticulocytes were positive for VLA‐4, while VLA‐4 staining of non‐SCD reticulocytes was undetectable. Titrations with natalizumab revealed the presence of saturable levels of VLA‐4 on both SCD reticulocytes and leucocytes similar to healthy subject leucocytes. Under physiological flow conditions, the adhesion of SCD whole blood cells and isolated SCD leucocytes to immobilized vascular cell adhesion molecule 1 (VCAM‐1) was blocked by natalizumab in a dose‐dependent manner, which correlated with cell surface receptor binding. Natalizumab also inhibited >50% of whole blood cell binding to TNF‐α activated human umbilical vein endothelial cell monolayers under physiological flow at clinically relevant concentrations (10 to 100 μg/ml). This indicates that VLA‐4 is the dominant receptor that drives SCD reticulocyte and mononuclear cell adhesion to VCAM‐1 and that the VLA‐4 adhesion to VCAM‐1 is a significant contributor to SCD blood cell adhesion to endothelium. Thus, VLA‐4 blockade may be beneficial in sickle cell disease.
Managing Controversies in the Fuzzy Front End
Authors: Christiansen John K. , Gasparin Marta
Published: June 2016

This research investigates the controversies that emerge in the fuzzy front end (FFE) and how they are closed so the innovation process can move on. The fuzzy front has been characterized in the literature as a very critical phase, but controversies in the FFE have not been studied before. The analysis investigates the microprocesses around the controversies that emerge during the fuzzy front end of four products. Five different types of controversies are identified: profit, production, design, brand and customers/market. Each controversy represents a threat, but also an opportunity to search for new solutions in the unpredictable non‐linear processes. The study uses an ethnographic approach using qualitative data from interviews, company documents, external communication and marketing material, minutes of meetings, informal conversations and observations. The analysis of four FFE processes demonstrates how the fuzzy front requires managers to deal with controversies that emerge from many different places and involve both human and non‐human actors. Closing the controversies requires managers to take account of the situation, identify the problem that needs to be addressed, and initiate a search for solutions. Management is actively involved in this process, in many different ways. Among the implications from this analysis is that the managers' role in the FFE is multifaceted and each controversy seems to require different skills and competencies.
A Twin Factor Mixture Modeling Approach to Childhood Temperament: Differential Heritability
Authors: Scott Brandon G. , Lemery‐Chalfant Kathryn , Clifford Sierra , Tein Jenn‐Yun , Stoll Ryan , Goldsmith H.Hill
Published: June 2016

Twin factor mixture modeling was used to identify temperament profiles while simultaneously estimating a latent factor model for each profile with a sample of 787 twin pairs (Mage = 7.4 years,SD = .84; 49% female; 88.3% Caucasian), using mother‐ and father‐reported temperament. A four‐profile, one‐factor model fit the data well. Profiles included “regulated, typical reactive,” “well‐regulated, positive reactive,” “regulated, surgent,” and “dysregulated, negative reactive.” All profiles were heritable, with lower heritability and shared environment also contributing to membership in the “regulated, typical reactive” and “dysregulated, negative reactive” profiles.
The ongoing challenge of discrepant growth hormone and insulin‐like growth factor I results in the evaluation of treated acromegalic patients: a systematic review and meta‐analysis
Authors: Kanakis G.A. , Chrisoulidou A. , Bargiota A. , Efstathiadou Z.A. , Papanastasiou L. , Theodoropoulou A. , Tigas S.K. , Vassiliadi D.A. , Tsagarakis S. , Alevizaki M.
Published: June 2016

Objective

Growth hormone (GH) and insulin‐like growth factor I (IGF‐I) are the principal biomarkers used to assess disease activity in acromegaly, and any discrepancy between them renders interpretation of results inconclusive. Purpose of this study was to assess the frequency of this discrepancy and identify parameters that might affect its occurrence.

Design

A systematic review of MEDLINE and Scopus was performed (1987–2013) followed by a meta‐analysis to address the frequency of discrepant results between GH and IGF‐I levels. Meta‐regression and subgroup analyses were performed assessing the effects of the year of publication, the different types of GH testing and GH assays used, as well as the impact of treatment with somatostatin analogues (SSAs) on the occurrence of this discrepancy.

Results

The analysis retrieved 39 eligible studies totalling 7071 patients. The pooled discordance rate between GH and IGF‐I was 25·7% (95% CI: 22·3–29·4), and the predominant format was that of elevated IGF‐I with normal GH levels (15·3%, 95% CI: 12·5–18·7). No significant correlation between the discordance rate and the year of publication was shown; whereas, the use of ultrasensitive GH assays resulted in higher discordance rates (30·7%, 95% CI: 25·9–35·9 vs 19·8%, 95% CI: 14·1–27·2, P = 0·04) as did treatment with SSAs (32·5%, 95% CI: 27·8–37·4) vs (21·6%, 95% CI: 17·8–25·6, P = 0·001).

Conclusions

Discrepancy between GH and IGF‐I results is encountered in a quarter of treated patients with acromegaly, especially when using ultrasensitive GH assays or in patients receiving SSAs, a fact that the clinician should take into consideration when making clinical decisions.
Treatment of hyperthyroidism with antithyroid drugs corrects mild neutropenia in Graves' disease
Authors: Aggarwal N. , Tee S. A. , Saqib W. , Fretwell T. , Summerfield G.P. , Razvi S.
Published: June 2016

Context

Neutropenia secondary to antithyroid drug (ATD) therapy in Graves' disease (GD) is well recognized. However, the effect of hyperthyroidism, prior to and after ATD therapy, on neutrophil counts in patients with GD is unclear.

Objective

To study the prevalence of neutropenia in newly diagnosed untreated GD and the effect of ATD on the neutrophil count.

Design

Prospective study from August 2010 to December 2014.

Setting

Endocrinology outpatient clinic in a single centre.

Patients

Consecutive patients (n = 206) with newly diagnosed GD.

Intervention

ATD therapy.

Main outcome measures

Prevalence and factors predicting neutropenia (<2 × 109/l) and change in neutrophil counts following ATD.

Results

At diagnosis, 29 (14·1%) of GD individuals had neutropenia. Non‐Caucasians [odds ratio (95% CI) of 4·06 (1·14–14·45), P = 0·03] and patients with higher serum thyroid hormone levels [OR 1·07 (1·02–1·13), P = 0·002 for serum FT3] were the only independent predictors of neutropenia. All patients with neutropenia had normalized blood neutrophil levels after achieving euthyroidism with ATD therapy. In patients in whom data were available posteuthyroidism (n = 149), change in neutrophil count after achieving euthyroidism was independently related to reduction in thyroid hormone levels (P < 0·01).

Conclusions

GD is associated with neutropenia in one in seven patients at diagnosis, especially in non‐Caucasians and those with higher serum thyroid hormone levels. Neutrophil counts increase with treatment with ATD and are related to reduction in thyroid hormone concentrations. It is therefore important to check neutrophil levels in newly diagnosed patients with GD prior to commencing ATD therapy as otherwise low levels may incorrectly be attributed to ATD therapy.
Interventions to improve supervised contact visits between children in out of home care and their parents: a systematic review
Authors: Bullen Tracey , Taplin Stephanie , McArthur Morag , Humphreys Cathy , Kertesz Margaret
Published: June 2016

Although the importance of contact between children in care and their parents, when safe, is accepted, there is limited research about supervised face‐to‐face contact. There is no literature that has systematically critiqued how supervised contact can be best delivered. The aim of this systematic review was to evaluate the evidence for interventions aimed at improving the quality of contact visits between parents and their children who are in out‐of‐home care. Twelve studies were included in this review. Each study was graded and assigned scores according to the presence or absence of each of seven criteria. The studies demonstrated key similarities in the types of interventions provided, although delivery varied across group, individual and educational interventions. Parents reported improved capacity to manage their emotions and parents' satisfaction with the programmes was high. Although there was a lack of large scale, methodologically rigorous studies with long‐term follow‐up, some promising findings were identified: the literature indicates individual family support and group programmes have the potential to improve parent–child relationships and the quality of contact visits. This review suggests that future studies build on current evidence by addressing their methodological limitations and evaluating interventions that can be tailored to meet the needs of individual families.
“Emplotted Narratives” and Structured “Behavioral Observations” Supporting the Diagnosis of Willis‐Ekbom Disease/Restless Legs Syndrome in Children with Neurodevelopmental Conditions
Authors: Ipsiroglu Osman S. , Beyzaei Nadia , Berger Mai , Wagner Alexandra L. , Dhalla Sophia , Garden Jennifer , Stockler Sylvia
Published: June 2016

Background

Willis‐Ekbom disease/restless legs syndrome (WED/RLS) seems to be a frequent cause of intractable chronic insomnia (ICI) but is under‐recognized in children/adolescents with neurodevelopmental conditions (NDCs), as many patients do not have the ability to express the underlying “urge‐to‐move”. In light of this, we aim to develop a protocol for behavioral observations supporting the diagnosis of WED/RLS.

Methods

We investigated 26 pediatric patients (age 1–16 years, median 8) with NDCs, ICI and evidence of familial WED/RLS employing (1) “emplotted narratives” for description of the various “urge‐to‐move” presentations and (2) self‐description and “behavioral observations” during a “suggested clinical immobilization test” (SCIT).

Results

Parental narratives reflected typical WED/RLS‐related “urge‐to‐move” symptoms during day‐, bed‐, and nighttime in all patients. Fifteen out of 26 patients could describe the “urge‐to‐move” during the SCIT. Ten out of 26 patients, unable to describe their symptoms due to cognitive disabilities, showed patterns of “relieving‐movements” upon observation. Sensory processing abnormalities were reported in all patients, with tactile sensitivities (26/26) (including shifted pain threshold) as the most common sensory domain.

Conclusion

“Emplotted narratives” and structured “behavioral observations” support recognition of familial WED/RLS associated movement patterns and provide a useful tool for the diagnosis of WED/RLS in children with NDCs in a clinical office setting.
Transplantation from haploidentical donor is not inferior to that from identical sibling donor for patients with chronic myeloid leukemia in blast crisis or chronic phase from blast crisis
Authors: Ma Yan‐Ru , Huang Xiao‐Jun , Xu Zheng‐Li , Liu Kai‐Yan , Chen Huan , Zhang Xiao‐Hui , Han Wei , Chen Yu‐Hong , Wang Feng‐Rong , Wang Jing‐Zhi , Wang Yu , Chen Yao , Yan Chen‐Hua , Xu Lan‐Ping
Published: June 2016

Objectives

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for chronic myeloid leukemia (CML) patients in blast crisis (BC), and haploidentical donors (HID) are immediately available for most patients. We compared the outcomes of HID transplantation with those of matched related donor (MRD) transplantation in a cohort study.

Patients and Methods

A total of 90 consecutive patients who received allogeneic HSCT because of CML‐BC were investigated retrospectively. A total of 67 patients underwent transplantation from HID and 23 from MRD. Survival outcomes were compared between the two cohorts.

Results

Of the 90 patients, 86 patients were engrafted. Three‐year overall survival (OS) and relapse‐free survival (RFS) were comparable between HID and MRD recipients (OS: 60.0% vs 55.3%, respectively, P=.580; RFS: 51.1% vs 47.8%, respectively, P=.512). Three‐year incidences of transplant‐related mortality (TRM) and relapse did not differ between HID and MRD recipients (relapse: 21.0% vs 26.1%, respectively, P=.626; TRM: 27.9% vs 26.1%, respectively, P=.937). In multivariate analyses, previous chemotherapy history and not achieving CHR before HSCT are independent adverse predictors of OS.

Conclusions

For CML‐blast crisis or chronic phase from blast crisis patients, HID transplantation achieves comparable survival to MRD transplantation. HID donors can be regarded as regular donors for these special patients at selected centers.
Macrovesicular steatosis in living related liver donors: correlation of biopsy findings with CT liver attenuation index and body mass index
Authors: Jehangir Maham , Nazir Rashed , Jang Aisha , Rana Atif , Rafique Salman , Dar Faisal Saud
Published: June 2016

Background

Hepatic steatosis threatens post‐transplant graft survival; therefore, pre‐operative quantification of steatosis is crucial. Gold standard for evaluation is donor liver biopsy but it is invasive. An alternative non‐invasive method is a calculation of CT liver attenuation index. BMI can be an independent factor predicting grade of steatosis but it is necessary to re‐define appropriate BMI cut‐off points that are specific for Asians.

Objective

To retrospectively analyze CT LAI and BMI for quantitative assessment of macrovesicular steatosis in living related liver donors, using histological analysis as gold standard.

Materials and Methods

A radiologist blinded to histological grading calculated mean CT hepatic attenuation in 48 potential living related liver donors.

Results

CT‐derived LAI correctly predicted steatosis in all except 1 patient. Parametric analysis for CT LAI and BMI showed overall weak positive correlation. No significant association was found between BMI and biopsy findings.

Conclusion

Liver biopsy remains a gold standard for evaluation of steatosis. CT LAI of ≤0 correlates well with significant hepatic steatosis and biopsy may be avoided in such cases. Biopsy may be reserved for patients with CT LAI between 1 and 5. BMI alone is not a good predictor of hepatic steatosis in our study population.
Patient‐reported outcomes in liver transplant recipients with hepatocellular carcinoma
Authors: Kensinger Clark D. , Feurer Irene D. , O'Dell Heather W. , LaNeve David C. , Simmons Lindsey , Pinson C. Wright , Moore Derek E.
Published: June 2016

Background

The effect of awarding MELD exception points for hepatocellular carcinoma (HCC) on patient‐reported outcomes (PROs) is unknown. We evaluated the physical and mental health‐related quality of life (HRQOL) and symptoms of anxiety and depression in liver transplant recipients with HCC compared to patients without HCC.

Methods

The single‐center sample measured PROs before and after transplant, which included 1521 multisurvey measurement points among 502 adults (67% male, 28% HCC, follow‐up time: <1–131 months). Data were analyzed using multivariable mixed‐effects models.

Results

Longitudinal PRO values did not differ between persons who received HCC exception points and those who did not have HCC. Patients with HCC who did not receive exception points had reduced physical HRQOL (P=.016), a late decline in mental HRQOL, and delayed reduction in anxiety (time‐by‐outcome interaction P<.050) compared to patients with HCC who received exception points.

Conclusion

Transplant recipients who received HCC exception points had PROs that were comparable to those of patients without HCC, and reported better physical HRQOL and reduced symptoms of anxiety compared to patients with HCC who did not receive exception points. These analyses demonstrate the impact of HCC exception points on PROs, and may help inform policy regarding HCC exception point allocation.
Pharmacokinetics and pharmacodynamics of dapagliflozin in children and adolescents with type 2 diabetes mellitus
Authors: Tirucherai G. S. , LaCreta F. , Ismat F. A. , Tang W. , Boulton D. W.
Published: June 2016

Aims

To evaluate the pharmacokinetic (PK)/pharmacodynamic (PD) and safety profile of dapagliflozin in paediatric patients aged 10–17 years with type 2 diabetes mellitus (T2DM).

Methods

Patients were randomized to a single oral dose of dapagliflozin 2.5, 5 or 10 mg. The PK characteristics for individual patients were derived by non‐compartmental methods. Urinary glucose excretion (UGE), fasting plasma glucose (FPG) and ease of swallowing were also evaluated.

Results

A total of 24 patients with a mean (range) body weight of 99.7 (61.5–169.5) kg received dapagliflozin. Dapagliflozin was rapidly absorbed after oral administration (median time to maximum plasma concentration ∼1.5 h) and systemic exposures to dapagliflozin and its 3‐O‐glucuronide metabolite appeared dose‐proportional. The mean 24‐h UGE increased in a dose‐related manner (52.8, 62.4 and 89.0 g for the 2.5, 5 and 10 mg groups, respectively). Mean FPG concentrations were lower for all dose groups on day 2 (6.9, 6.2 and 6.8 mmol/l for 2.5, 5 and 10 mg groups, respectively) than they were predose on day 1 (9.5, 8.5 and 8.2 mmol/l for 2.5, 5 and 10 mg groups, respectively). Six patients (25%) experienced ≥1 adverse event (AE), however, there was no dose‐related pattern. All AEs occurred only once and most were mild in intensity. Nearly all patients (n = 23; 95.8%) reported easy swallowing of the dapagliflozin tablets.

Conclusions

Dapagliflozin was well tolerated in this paediatric population, with no significant safety findings. PK/PD characteristics were similar to those observed in adults with T2DM, thereby supporting the hypothesis that the same dapagliflozin dosage as that used in adults can be evaluated in future phase III paediatric studies.
PUBLIC INFRASTRUCTURE MAINTENANCE AND THE DISTRIBUTION OF WEALTH
Authors: Gibson John , Rioja Felix
Published: June 2016

When considering how to allocate scarce resources for the development of public infrastructure, many countries have a tendency to neglect maintenance in favor of new infrastructure investment projects. We examine the role of maintenance expenditures on output and on the distribution of wealth in a heterogeneous agents model. In our model, maintenance affects the quality of existing infrastructure and thus the flow of services derived from it. Furthermore, maintenance expenditures also affect the depreciation rates of both public infrastructure and private capital. We calibrate our model to Mexico and consider several policies that increase the flow of resources to infrastructure and find that a policy that allocates all additional resources to new investment is dominated by policies that allocate at least some of the additional resources to maintenance. Specifically, focusing all additional resources on maintenance is shown to generate the largest reduction in inequality, while a more balanced policy that increases both investment and maintenance maximizes output growth. (JEL E00, E62, H54)
Is behaviour in a novel environment associated with bodily state in brown troutSalmo truttafry?
Authors: Näslund Joacim , Sandquist Lin , Johnsson Jörgen I.
Published: June 2016

Energetic status and body size are inconstant bodily states often considered to have feedback effects on behaviour. Feedbacks can be negative, like starvation‐threshold feedbacks (lower state values = increased risk taking due to higher energy need, and vice versa), or positive, like state‐dependent safety feedbacks (higher state values = lower vulnerability when expressing risky behaviours, and vice versa). Few studies have investigated feedback effects during the early‐life survival bottleneck of territorial species, when rapid growth is particularly important to maintain competitive ability. We investigated effects of body size and energetic status on the emergence latency into an unknown environment in highly territorial brown trout fry. We manipulated energetic status using high and low food rations in different combinations over two consecutive periods. In contrast to results from other small‐sized fishes, no general behavioural effects of energetic state were detected, but larger fish had on average shorter emergence latency. Starvation‐threshold feedbacks were not supported, but the size effect favours the presence of a state‐dependent safety feedback. When individuals were split into clusters characterised by long (>34 s) and short (<34 s) emergence latency, a state‐dependent safety feedback, based on energetic status, was found in the short‐latency cluster. Positive state‐dependent feedbacks may reflect the high level of competition among wild trout fry during the first summer, particularly among the more active individuals (i.e., from the short latency cluster). High state levels could be utilised to gain advantages over lesser competitors (e.g., to establish territories), particularly if the overall risk of starvation is higher than the risk of predation.
Partnering to change the world for people with haemophilia: 6th Haemophilia Global Summit, Prague, Czech Republic, 24–26th September 2015
Authors: Astermark Jan , Hart Dan , Lobet Sébastien , Blatný Jan , d'Oiron Roseline , Kenet Gili , Dolan Gerry , Libotte Valérie , Hermans Cedric
Published: June 2016

The 6th Haemophilia Global Summit was held in Prague, Czech Republic, in September 2015. The programme was designed by an independent Scientific Steering Committee of haemophilia experts and aimed to share optimal management strategies for haemophilia at all life stages, explore recent potential advances in the management of haemophilia A and B and discuss challenges in haemophilia care. In this supplement from the meeting, Dan Hart reviews the lessons that can be learnt from cost‐constrained environments with regard to improving care for people with haemophilia globally. Sébastien Lobet discusses the importance of physical activity for optimising care and Roseline d'Oiron and Jan Blatný consider the role of real‐world data in understanding the effect of treatment in a clinical setting over the long term and the true impact of treatment on the day‐to‐day life of the patient. Gili Kenet addresses the current challenges relating to the optimal management of prophylaxis, and Gerry Dolan and Cedric Hermans discuss the value of pharmacokinetic (PK) parameters in informing treatment decisions. Cedric Hermans and Valérie Libotte explore the importance of considering social and occupational development factors as an integral part of haemophilia care, and Jan Astermark reviews key strategies to predict and prevent inhibitor development.
Mirror, Mirror on the Wall: Identity‐Image Interactions for the Sales Force in High Threat Situations
Authors: Rodrigues Caren , Krishnamurthy Anup
Published: June 2016

During times of threat to organizational identity, managers often formulate strategies to regain the organization's original standing. Yet, they frequently ignore the identity‐image interactions that occur for boundary‐spanning members, despite such interactions having the potential to play a pivotal role in the organization's recovery. We propose that, in high‐threat situations, customer‐directed boundary‐spanners, like the sales force, become aware of the discrepancy between the organizational image projected by the organization (Projected Image) and the organizational image perceived by customers (Perceived Image). Consequently, boundary‐spanners restructure their perception of the organizational identity. This restructuring is moderated by several factors. The restructured organizational identity results in the boundary‐spanner manifesting a new projected image, with its attendant assertions and behaviors. We thus synthesize and extend the literature on identity‐image interactions and provide avenues for further research. We also discuss the beneficial managerial implications of closely monitoring the image‐identity interactions of boundary‐spanners in high threat situations.
Effects of chemical and microbial additives on clostridium development in sugarcane (Saccharum officinarum L.) ensiled with lime
Authors: Custódio Letícia , Morais Greiciele , Daniel João L. P. , Pauly Thomas , Nussio Luiz G.
Published: June 2016

The aim of this study was to compare strategies to prevent clostridium growth in sugarcane silages added with lime. In Experiment 1, treatments were (as fed basis): no additives (Control), 15 g lime kg−1 (L), 15 g lime kg−1 + 1.5 g sodium benzoate kg−1 (L+B), 15 g lime kg−1 + 0.7 g sodium nitrite kg−1 (L+N), 15 g lime kg−1 + Lactobacillus buchneri (5 × 105 cfu g−1) (L+LB) and 15 g lime kg−1 + Lactobacillus plantarum (5 × 105 cfu g−1) (L+LP). Plastic buckets (20 L) were used as experimental silos. Silage fermentative losses and aerobic stability were also evaluated. Lime treatment was not effective in decreasing dry matter (DM) losses compared with control silage (121 and 158 g kg−1, respectively). On the other hand, L+LB, L+B, L+LP and L+N treatments significantly decreased DM losses (70, 73, 87 and 98 g kg−1, respectively). The aerobic stability of silages L (172 h), L+B (155 h) and L+N (223 h) was substantially higher compared to those treated with L+LB (49 h), L+LP (48 h) and control (52 h). Control silages had low counts of clostridia (log 3.3 cfu g−1) whereas L and L+LB treated silages reached very high clostridium counts (log 6.7 and log 6.0 cfu g−1, respectively). The remaining treatments resulted in intermediate values. In Experiment 2, sugarcane treated with lime (15 g kg−1) received the following doses of sodium nitrite prior to ensiling: 0, 0.5, 1.0 and 1.5 g kg−1 as fed. Treatments did not affect clostridium counts but decreased butyric acid and 2,3‐butanediol. The silage with the highest nitrite dose decreased the butyric acid content substantially compared to other treatments but the final level (5.9 g kg−1 DM) was above the target value for well‐fermented silage. None of additives combined with lime were able to provide completely butyric acid free silages.
Identification of mutations in theF8andF9gene in families with haemophilia using targeted high‐throughput sequencing
Authors: Lyu C. , Xue F. , Liu X. , Liu W. , Fu R. , Sun T. , Wu R. , Zhang L. , Li H. , Zhang D. , Yang R. , Zhang L.
Published: June 2016

Introduction

At present, many methods are available for the genetic diagnosis of haemophilia, including indirect linkage analysis, direct sequencing. However, these methods are time‐consuming, labourious, and limited in their application. Therefore, the development of new, more effective techniques is necessary.

Aim

To detect theF8andF9gene mutations in patients with haemophilia and their female relatives in 29 haemophilia A (HA) and 11 haemophilia B (HB) families.

Methods

FVIII:C and FIX:C were analyzed using one‐stage method, and factor VIII and factor IX inhibitors were tested using the Bethesda method. Intron 22 and one inversions were identified using long‐distance polymerase chain reaction (PCR) and standardPCR. Non‐inversion mutations of theF8andF9gene were identified by targeted high‐throughput sequencing. All mutations were verified by Sanger sequencing.

Results

Intron 22 inversion was detected in eightHAfamilies and intron one inversion was detected in oneHAfamily. Apart from the inversion mutations, 20 mutations were identified inHAfamilies, including 17 previously reported and three novel mutations: c.5724G>A (p.Trp1908*), c.6116‐1_6120delGAGTGTinsTCC(p.Lys2039Ilefs*13), and c.5220‐2A>C. We found a complex rearrangement inHA: intron one inversion concomitant with exon one deletion. InHB, eight recurrent mutations were detected, including six missense mutations and two nonsense mutations.

Conclusion

Targeted high‐throughput sequencing is an effective technique to detect theF8andF9gene mutations, especially for the discovery of novel mutations. The method is highly accurate, time‐saving and shows great advantage in uncovering large deletion mutations and also in distinguishing the wild‐type genotype and heterozygous large deletions.
Practical aspects of factor concentrate use in patients with von Willebrand disease undergoing invasive procedures: a European survey
Authors: Windyga J. , Dolan G. , Altisent C. , Katsarou O. , López Fernández M.‐F. , Zülfikar B. ,   the EHTSB
Published: June 2016

Introduction

The bleeding propensity in von Willebrand disease (VWD) is usually moderate or mild and patients with VWD do not need continuous treatment, but do require extra increased haemostatic cover when undergoing dental or surgical procedures. Desmopressin can be effective in certain patient groups and this has been considered in a previous publication.

Aim

This paper now seeks to evaluate current knowledge and practice in the use of factor concentrate in the management of VWD patients undergoing invasive procedures.

Methods

A literature search was performed on the use of factor concentrates to cover invasive procedures and a survey of current practice in a number of specialist haematology centres across Europe represented by the European Haemophilia Strategy Board was conducted.

Results

Our review of the literature and the results of the survey showed considerable heterogeneity in treatment regimens, and a lack of consistency in reporting of the variables that determine factor concentrate dosing and monitoring.

Conclusion

By analysing the literature, examining guidelines and using consensus deliberation, this survey allowed the group to develop recommendations for management of VWD patients undergoing invasive procedures.
Can the phenotype of inherited fibrinogen disorders be predicted?
Authors: Casini A. , de Moerloose P.
Published: June 2016

Congenital fibrinogen disorders are rare diseases affecting either the quantity (afibrinogenaemia and hypofibrinogenaemia) or the quality (dysfibrinogenaemia) or both (hypodysfibrinogenaemia) of fibrinogen. In addition to bleeding, unexpected thrombosis, spontaneous spleen ruptures, painful bone cysts and intrahepatic inclusions can complicate the clinical course of patients with quantitative fibrinogen disorders. Clinical manifestations of dysfibrinogenaemia include absence of symptoms, major bleeding or thrombosis as well as systemic amyloidosis. Although the diagnosis of any type of congenital fibrinogen disorders is usually not too difficult with the help of conventional laboratory tests completed by genetic studies, the correlation between all available tests and the clinical manifestations is more problematic in many cases. Improving accuracy of diagnosis, performing genotype, analysing function of fibrinogen variants and carefully investigating the personal and familial histories may lead to a better assessment of patients' phenotype and therefore help in identifying patients at increased risk of adverse clinical outcomes. This review provides an update of various tests (conventional and global assays, molecular testing, fibrin clot analysis) and clinical features, which may help to better predict the phenotype of the different types of congenital fibrinogen disorders.
Usefulness of the Total Thrombus‐Formation Analysis System (T‐TAS) in the diagnosis and characterization of von Willebrand disease
Authors: Daidone V. , Barbon G. , Cattini M. G. , Pontara E. , Romualdi C. , Di Pasquale I. , Hosokawa K. , Casonato A.
Published: June 2016

Introduction

The heterogeneity of von Willebrand disease (VWD) makes its diagnosis a difficult task.

Methods

We report here on the usefulness of a microchip‐based flow‐chamber system, the total thrombus‐formation analysis system (T‐TAS), in the identification and characterization of VWD. Thirty VWD patients and 20 healthy subjects were studied with the T‐TAS platelet (PL) and atherome (AR) microchips developed for the in vitro assessment of platelet thrombus formation and fibrin‐rich platelet thrombus formation respectively.

Results

Samples from severe type 1 VWD, characterized by von Willebrand factor (VWF) levels below 10 U dL−1, failed to occlude either the PL or the AR chip capillaries, while the occlusion times were normal in patients with mild type 1 VWD (VWF above 25 U dL−1). PL and/or AR chip occlusion occurred, but took longer than normal, for samples from type Vicenza and type 1 VWD patients, whose VWF levels ranged between 10 and 25 U dL−1. No PL or AR chip capillary occlusion was seen for samples from patients with type 2A or 2B VWD featuring the absence of large VWF multimers, whereas no abnormalities emerged for type 2B patients with normal multimer patterns.

Conclusion

The T‐TAS appears to be sensitive mainly to plasma VWF concentration and the presence of large multimers. Failure of the PL and AR chips to become occluded points to a lack of large VWF multimers, or type 1 VWD with VWF levels below 10 U dL−1. Although the T‐TAS does not assure a precise VWD diagnosis, it does point us in the right direction, and thus seems a useful global preliminary test.
The potential of educational comics as a health information medium
Authors: McNicol Sarah
Published: June 2016

Objectives

To investigate ways in which educational comics might provide support in dealing with feelings and attitudes towards health conditions, as well as improving understanding of factual information and to identify potential weakness of comics as a medium for health information.

Methods

Semi‐structured interviewees with eleven university students who either had a mental or physical health condition themselves or had a family member with a health condition.

Results

The result highlighted the potential value of comics as a format for health information. In addition to conveying factual information, comics offer opportunities for self‐awareness, reassurance, empathy, companionship and a means to explore the impact of illness on family relationships. However, there are notable barriers to the greater use of comics to provide health information, namely, a lack of awareness of, and easy access to, educational comics, along with the perception that comics are exclusively light‐hearted and for children.

Conclusions

Currently, the full potential of comics in health settings is not being realised. Health information professionals may be in a position to address this issue through identifying, cataloguing, indexing and promoting comics as a legitimate format for health information.
Loss of p53 expression is accompanied by upregulation of beta‐catenin in meningiomas: a concomitant reciprocal expression
Authors: Pećina‐Šlaus Nives , Kafka Anja , Vladušić Tomislav , Tomas Davor , Logara Monika , Skoko Josip , Hrašćan Reno
Published: June 2016

Crosstalk between Wnt and p53 signalling pathways in cancer has long been suggested. Therefore in this study we have investigated the involvement of these pathways in meningiomas by analysing their main effector molecules, beta‐catenin and p53. Cellular expression of p53 and beta‐catenin proteins and genetic changes in TP53 were analysed by immunohistochemistry, PCR/RFLP and direct sequencing of TP53 exon 4. All the findings were analysed statistically. Our analysis showed that 47.5% of the 59 meningiomas demonstrated loss of expression of p53 protein. Moderate and strong p53 expression in the nuclei was observed in 8.5% and 6.8% of meningiomas respectively. Gross deletion of TP53 gene was observed in one meningioma, but nucleotide alterations were observed in 35.7% of meningiomas. In contrast, beta‐catenin, the main Wnt signalling molecule, was upregulated in 71.2%, while strong expression was observed in 28.8% of meningiomas. The concomitant expressions of p53 and beta‐catenin were investigated in the same patients. In the analysed meningiomas, the levels of the two proteins were significantly negatively correlated (P = 0.002). This indicates that meningiomas with lost p53 upregulate beta‐catenin and activate Wnt signalling. Besides showing the reciprocal relationship between proteins, we also showed that the expression of p53 was significantly (P = 0.021) associated with higher meningioma grades (II and III), while beta‐catenin upregulation was not associated with malignancy grades. Additionally, women exhibited significantly higher values of p53 loss when compared to males (P = 0.005). Our findings provide novel information about p53 involvement in meningeal brain tumours and reveal the complex relationship between Wnt and p53 signalling, they suggest an important role for beta‐catenin in these tumours.
Study on the physicochemical properties and in vitro digestibility of starch from yam with different drying methods
Authors: Chen Xuetao , Mao Xinhui , Jiang Qianqian , Wang Tingting , Li Xia , Gao Wenyuan
Published: June 2016

Four methods were applied to dry yam slices, and then, starches were isolated from dried yam slices. Starch isolated from fresh yam was as the study control, and physicochemical properties and in vitro digestibility of starches were studied. The results showed that the amylose content ranged from 12.62% to 28.25%, water‐binding capacity (WBC) from 111.67% to 262.88%, paste clarity from 2.1% to 6.23%, resistant starch (RS) from 66.60% to 88.49% and crystallinity from 11.27% to 25.52%. Compared with the control starch, hot air‐drying at 60 °C significantly decreased amylose content, paste clarity, RS and crystallinity, while increasing the WBC. Low levels of rapidly digestible starch and glucose and high RS levels were found in the starch from freeze‐drying yam. Digestibility of the starches was significantly correlated with amylose content, WBC, paste clarity and swelling power. The starch samples were divided into three groups by principal component analysis (PCA).
A transnational feminist policy analysis of the Trafficking Victims Protection Act
Authors: Noyori‐Corbett Chie , Moxley David P.
Published: June 2016

A transnational feminist policy analysis of the Trafficking Victims Protection Act: Noyori‐Corbett C., Moxley D.P. A transnational feminist policy analysis of the Trafficking Victims Protection Act

Although originally the Trafficking Victims Protection Act (TVPA) sought to prosecute traffickers, protect victims, and prevent trafficking, the most essential aim of the act involving prevention, especially in victims’ countries of origin, has not been dominant in combating trafficking. The authors used a transnational feminist framework of policy analysis to reveal the TVPA's limitations in addressing the diminished status of poor women in the developing world. Using five key questions emanating from transnational feminism, the authors illuminate the extent to which the act is unresponsive to the economic realities that make women in developing countries vulnerable to human trafficking. Based on their analysis, the authors offer considerations for the future re‐authorization of the Act, emphasizing a shift from a paradigm involving the criminalization of victims to one embodying prevention.
A room for design: Through participatory design young adults with schizophrenia become strong collaborators
Authors: Terp Malene , Laursen Birgitte Schantz , Jørgensen Rikke , Mainz Jan , Bjørnes Charlotte D.
Published: June 2016

Smartphone technology is being increasingly viewed as key to engaging young adults with schizophrenia in their own mental health care.

In an attempt to use smartphones as an engagement tool, we conducted a participatory design process, where young adults with schizophrenia (n = 4), healthcare providers (n = 7), software designers (n = 3), graphic designer (n = 1), graphic recorder (n = 1), and team leader (n = 1) co‐designed a smartphone application for use in early phase schizophrenia care.

This paper reports the co‐design process. Based on a variety of written data‐sources, the paper describes if, and how, participatory design can help construct a physical and relational environment that enables young adults with schizophrenia to become active participants in the design of a more participatory mental health practice.

Guided by Etienne Wenger's construct of Community of Practice, three major categories of characteristics and construction of a physical and relational environment supporting and inspiring participation and engagement were identified: (i) a pre‐narrative about a community of practice, (ii) the room for design is a community of practice and (iii) the community of practice as a practice of special qualities. It is concluded that participatory design can support and inspire participation and engagement in the development of mental health care with young adults with schizophrenia, given that the environment in which participatory design unfolds is transparent, flexible, secure and informal.
Consumer attitudes towards evidence based mental health services among American mental health consumers
Authors: Teh Lisa B. , Hayashi Kentaro , Latner Janet , Mueller Charles W.
Published: June 2016

The Consumer Attitudes towards Evidence Based Services (CAEBS) scale is a 29‐item questionnaire designed to assess public views on the role of science in helping to guide mental health treatment. The aim of the current study was to assess the Factor structure the CAEBS in an online sample of adults seeking information about mental health services. The CAEBS was administered to a nationwide sample of participants from websites offering classified advertisements for mental health related study participation (n = 312). An Exploratory Factor Analysis (EFA) suggested four factors based on 26 of the items: Beliefs Regarding Therapists' Practices, Attitudes about Mental Health Policy, Negative Personal‐Level Attitudes toward EBPs, and Negative Societal‐Level Attitudes towards EBPs. In order to increase consumer empowerment within the mental health‐care system and develop policies supporting EBP usage, mental health professionals need to increase communication with the public to address these concerns and leverage positive attitudes.
Development and validation of the Nursing Profession Self‐Efficacy Scale
Authors: Caruso R. , Pittella F. , Zaghini F. , Fida R. , Sili A.
Published: June 2016

Aim

This study describes the development and validation of the Nursing Profession Self‐Efficacy Scale.

Background

Self‐efficacy can be useful in predicting performance, job satisfaction or well‐being. In the nursing field, there is a shortage of studies on self‐efficacy with regard to nurses’ global confidence in coping ability across a range of everyday, challenging work situations.

Methods

To define the theoretical framework of nursing professional self‐efficacy, two focus groups and a literature review were performed. An empirical study was then conducted to test validity and reliability. Face and content validity, construct validity, concurrent validity, internal consistency and test–retest reliability were examined. The content validity index was evaluated by 12 experts who suggested deleting 11 redundant items. The final developed tool was tested for construct analysis using a cross‐validation approach, randomly splitting the overall sample of 917 nurses in two sub‐groups.

Findings

The construct validity indicated two dimensions. The face and content validity were adequate. Test–retest reliability displayed a good stability, and internal consistency (Cronbach's α) was acceptable. Moreover, concurrent validity using the Generalized Self‐Efficacy Scale was in line with the theoretical framework.

Conclusion

The scale showed evidence of validity and reliability. The major limitation is the strong influence of the Italian context in the tool development.

Implications for nursing and health policy

The Nursing Profession Self‐Efficacy Scale could be a fruitful tool that facilitates the application of theories (i.e. social‐cognitive theory) in the nursing field and even development of interventions. Furthermore, a measurement of self‐efficacy could be used to predict nursing clinical performance.