bluuebunny/crossref_metadata_2025 huggingface dataset:
A Maxwell's fish eye lens for the terahertz region
Authors: Liu Jingbo , Mendis Rajind , Mittleman Daniel M.
Published: July 2013

We implement a two-dimensional Maxwell's fish eye lens using a waveguide-based artificial dielectric. The Maxwell's fish eye lens consists of two metallic cylindrical plates sandwiching a free-space region, with the inner surface of one plate shaped into a hollow conical form. This lens has the capability to image terahertz beams from a source located at the edge (between the plates) to the diametrically opposite point on the edge, independent of the incident angle.
Active steps towards a healthier life for people with severe mental illness: a qualitative approach to understanding the potential for implementing change
Authors: Ehrlich Carolyn , Kisely Steve , Kendall Elizabeth , Crompton David , Crowe Elizabeth , Liddy Ann Maree
Published: July 2013

Objective.
Our health systems are failing to provide optimal physical care for people with severe mental illness. To address this gap, Queensland Health and General Practice Queensland in partnership developed a comprehensive package of guidelines and health messages. However, guidelines alone are likely to be inadequate motivators of change. The objective of this research was to qualitatively explore key stakeholders’ expectations about the implementation of guidelines, with the purpose of identifying potential interventions to support practice change.

Method.
Participants were recruited from the partnership governance committee. A semistructured interview guide was used to gather data. Using grounded-theory techniques, the data were analysed to identify key themes.

Results.
All stakeholders agreed that the purpose of developing comprehensive guidelines and health messages was to achieve change through innovation and the promotion of early intervention, reduction of avoidable admissions and sectoral integration. However, existing structures within the system were considered to be insurmountable barriers.

Conclusion.
Key stakeholders sought broader change than just guidelines and health messages developed by the partnership focussed specifically on awareness-raising about the physical care of people with severe mental illness. However, there was no clear consensus as to what that change should be. This mismatch between the goals and actions of such a large-scale initiative is problematic. Suggestions are made about how to address change.

What is known about the topic?
The physical and oral health of people with severe mental illness is poor. One response that is frequently used to improve the health of this population is to develop and implement guidelines for practice. However, oral healthcare is frequently omitted from guidelines for care. Moreover, guidelines are not always adopted in everyday practice.

What does this paper add?
This paper outlines a process of guideline development and includes investigation of the short- and long-term goals that a governing committee held for the implementation of guidelines for both the physical and oral healthcare of people with severe mental illness. Additionally, we explore gaps between a short-term focus for guideline implementation and the longer-term goals of achieving improved healthcare.

What are the implications for practitioners?
Cultural change is required if the physical and oral health of people with severe mental illness is to be improved. However, a mismatch between the goals and actions of large-scale initiatives is problematic. Thus, clearly identified avenues for realising long-term culture change are required if new practices are to be embedded in everyday routines.

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Environmental Mass Spectrometry in the North American Great Lakes Fish Monitoring and Surveillance Program
Authors: Crimmins Bernard S. , Pagano James J. , Milligan Michael S. , Holsen Thomas M.
Published: July 2013

The Great Lakes Fish Monitoring and Surveillance Program (GLFMSP) has served to protect the Laurentian Great Lakes of North America for decades. Top predator fish from each lake are employed as bioindicators of chemical stressors within each lake. While a vast database has been created for legacy contaminants, such as polychlorinated biphenyls and organochlorine pesticides, a recent programmatic shift has transformed GLFMSP into a more proactive new chemical discovery/screening endeavour to capture the burden of more contemporary chemicals in the environment. The transition prompted the need for advanced instrumentation and the evaluation of mass spectrometric approaches beyond traditional electron capture detection and unit mass resolution mass spectrometers. Here the advances in detection methods are documented and the current direction of the program in creating a living database of anthropogenic chemicals affecting Great Lakes fish is highlighted.
Dinuclear Cu(II) 1,2,3-Triazole-Bridged Complex with Ferromagnetic Coupling
Authors: Bai Shi-Qiang , Jiang Lu , Zuo Jing-Lin , Yan Chun-Hua , Hor T. S. Andy
Published: July 2013

A new dinuclear Cu(ii) complex [Cu2Cl4(L1)2] (1) (L1 = 1-(2-picolyl)-4-hexyl-1H-1,2,3-triazole) has been synthesised and characterised by single-crystal X-ray diffraction (XRD) and powder XRD, thermogravimetric analysis, electron paramagnetic resonance spectrum, photoluminescence, and magnetic measurements. Complex 1 shows double 1,2,3-triazoles bridging the dinuclear Cu2N4 moiety, in which the bridging N=N bond indicates basal-apical asymmetric mode with 112.6° torsion angle of Cu–N=N–Cu. Different from most azole-bridged dinuclear Cu(ii) with antiferromagnetic couplings, complex 1 shows an intramolecular weak ferromagnetic interaction (J = 0.91 cm–1).
The Fifth Element in Drug Design: Boron in Medicinal Chemistry
Authors: Kahlert Jan , Austin Christopher J. D. , Kassiou Michael , Rendina Louis M.
Published: July 2013

The unique chemistry of boron allows for the utilisation of novel building-blocks which are not traditionally found in medicinal chemistry. The pharmaceutical industry has begun to exploit boronic acid derivatives as new drugs and several research groups are also exploring 1,2-azaborines and icosahedral boranes known as carboranes as boron-based structural motifs, with great promise for innovative drug design. Recent advances in the medicinal chemistry of these three important boron moieties are highlighted and illustrated with selected examples.
Oligomycin A-induced inhibition of mitochondrial ATP-synthase activity suppresses boar sperm motility and in vitro capacitation achievement without modifying overall sperm energy levels
Authors: Ramió-Lluch Laura , Yeste Marc , Fernández-Novell Josep M. , Estrada Efrén , Rocha Luiz , Cebrián-Pérez José A. , Muiño-Blanco Teresa , Concha Ilona I. , Ramírez Alfredo , Rodríguez-Gil Joan E.
Published: July 2013

Incubation of boar spermatozoa in a capacitation medium with oligomycin A, a specific inhibitor of the F0 component of the mitochondrial ATP synthase, induced an immediate and almost complete immobilisation of cells. Oligomycin A also inhibited the ability of spermatozoa to achieve feasible in vitro capacitation (IVC), as measured through IVC-compatible changes in motility patterns, tyrosine phosphorylation levels of the acrosomal p32 protein, membrane fluidity and the ability of spermatozoa to achieve subsequent, progesterone-induced in vitro acrosome exocytosis (IVAE). Both inhibitory effects were caused without changes in the rhythm of O2 consumption, intracellular ATP levels or mitochondrial membrane potential (MMP). IVAE was accompanied by a fast and intense peak in O2 consumption and ATP levels in control spermatozoa. Oligomycin A also inhibited progesterone-induced IVAE as well as the concomitant peaks of O2 consumption and ATP levels. The effect of oligomycin on IVAE was also accompanied by concomitant alterations in the IVAE-induced changes on intracellular Ca2+ levels and MMP. Our results suggest that the oligomycin A-sensitive mitochondrial ATP-synthase activity is instrumental in the achievement of an adequate boar sperm motion pattern, IVC and IVAE. However, this effect seems not to be linked to changes in the overall maintenance of adequate energy levels in stages other than IVAE.
On the generalized Fischer-Burmeister merit function for the second-order cone complementarity problem
Authors: Pan Shaohua , Kum Sangho , Lim Yongdo , Chen Jein-Shan
Published: July 2013

It has been an open question whether the family of merit functionsψp (p>1)\psi _p\ (p>1), the generalized Fischer-Burmeister (FB) merit function, associated to the second-order cone is smooth or not. In this paper we answer it partly, and show thatψp\psi _pis smooth forp∈(1,4)p\in (1,4), and we provide the condition for its coerciveness. Numerical results are reported to illustrate the influence ofppon the performance of the merit function method based onψp\psi _p.
Complex phenological changes and their consequences in the breeding success of a migratory bird, the white storkCiconia ciconia
Authors: Gordo Oscar , Tryjanowski Piotr , Kosicki Jakub Z. , Fulín Miroslav
Published: July 2013

The timing of bird migration has shifted in response to climate change. However, few studies have linked the potential consequences of any phenological shift on individual fitness and even fewer have disentangled the role of plasticity and microevolution in the observed shifts.

The arrival date and breeding success of white storks (Ciconia ciconia) have been recorded since the 1880s in Slovakia. We used data for two periods (1895–1913 and 1977–2007), which were considered, respectively, as populations before and after the start of climate warming. About 4000 male and 2500 female arrival dates along with 3000 breeding attempts were studied.

Mean arrival dates did not differ between the two periods. During 1977–2007, males tended towards a slight delay for most fractions of arrival distribution. Protandry was reduced by 30% (1·44 days).

In both sexes, the early percentiles of the arrival distribution arrived later those years with warmer temperatures at the African wintering grounds, while late percentiles advanced their arrival when temperatures were higher in the European areas flown over during migration.

Mean breeding success of the Slovakian population has not changed since 1977. However, fecundity selection for arrival date reduced over the years: at the end of 1970s and 1980s, early breeders had more success than late breeders, but this seasonal trend disappeared towards the end of the study period. An early arrival and territory acquisition may have become less of an advantage due to the enhancement of feeding opportunities during the breeding season in recent decades.

A century ago, stork arrival varied spatially, with earlier arrivals at low altitudes, southern slopes and warmer and drier regions. This spatial variation mostly vanished, and at present, we found little correlations with topographical and climatic gradients.

We showed that long‐term temporal changes in the timing of biological events may be complex because each fraction of a population and sex may show different temporal trends in their arrival dates. In addition, the effect of biotic and abiotic factors may change consistently in space and time, and thereby phenotypes' value depends on the circumstances that are expressed due to its variable fitness consequences.
Marine protected areas facilitate parasite populations among four fished host species of central Chile
Authors: Wood Chelsea L. , Micheli Fiorenza , Fernández Miriam , Gelcich Stefan , Castilla Juan Carlos , Carvajal Juan
Published: July 2013

Parasites comprise a substantial proportion of global biodiversity and exert important ecological influences on hosts, communities and ecosystems, but our knowledge of how parasite populations respond to human impacts is in its infancy.

Here, we present the results of a natural experiment in which we used a system of highly successful marine protected areas and matched open‐access areas in central Chile to assess the influence of fishing‐driven biodiversity loss on parasites of exploited fish and invertebrate hosts. We measured the burden of gill parasites for two reef fishes (Cheilodactylus variegatus and Aplodactylus punctatus), trematode parasites for a keyhole limpet (Fissurella latimarginata), and pinnotherid pea crab parasites for a sea urchin (Loxechinus albus). We also measured host density for all four hosts.

We found that nearly all parasite species exhibited substantially greater density (# parasites m−2) in protected than in open‐access areas, but only one parasite species (a gill monogenean of C. variegatus) was more abundant within hosts collected from protected relative to open‐access areas.

These data indicate that fishing can drive declines in parasite abundance at the parasite population level by reducing the availability of habitat and resources for parasites, but less commonly affects the abundance of parasites at the infrapopulation level (within individual hosts).

Considering the substantial ecological role that many parasites play in marine communities, fishing and other human impacts could exert cryptic but important effects on marine community structure and ecosystem functioning via reductions in parasite abundance.
FORUM: Searching for biodiversity gains through woodfuel and forest management
Authors: Fuller Robert J.
Published: July 2013

Woodfuel extraction from established woods and forests is promoted in Western Europe as a renewable energy source. Woodfuel management is mainly carried out by silvicultural thinning or short‐rotation harvesting, including coppicing. Potential negative effects include reduction in habitat quality for saproxylic species. However, in some regions, habitats may be improved for species that have declined as a result of increased shading. Resources required by most of these species are more likely to be delivered by short‐rotation management than thinning.

Relatively little is documented on the effects of thinning intensity on ecological resources and biodiversity within European forests. Trade‐offs between canopy cover, deer browsing pressure and understorey complexity are likely to occur. Therefore, interactions between thinning treatments and deer browsing potentially affect biodiversity, in the context of both woodfuel and timber production.

Synthesis and applications. Woodfuel management is unlikely to deliver benefits for most shade‐intolerant species unless it creates substantial areas of young‐growth with low deer impacts. However, more research is needed on thinning as a potential conservation tool. Changing climate and tree diseases are creating an uncertain future for forest management. It is timely for ecologists to work with forest managers to identify how integrated forestry and deer management can deliver positive and balanced biodiversity outcomes.
Diachronic Change in Verbal Agreement Patterns withMajorité
Authors: Tristram Anna
Published: July 2013

This article is concerned with the description of data relating to a case of morphosyntactic variation and change in French: verbal agreement patterns with the nounmajorité‘majority’. Quantitative analysis of apparent‐time data from cloze (‘gap‐fill’) tests suggests that plural agreement with this noun is increasing; data from a diachronic corpus study confirm that this is the case. A number of factors are found to constrain this variation and change, including most importantly the presence and number of a post‐modifying noun phrase (e.g.la majorité des hommes). The implications of these findings for the definition of collective nouns in French are discussed.
Determination of optimal timing of 2,4‐dichlorophenoxyacetic acid foliar applications for common scab control in potato
Authors: Thompson H.K. , Tegg R.S. , Davies N.W. , Ross J.J. , Wilson C.R.
Published: July 2013

Application of 2,4‐dichlorophenoxyacetic acid (2,4‐D) has been shown to be an effective control method for common scab of potato. Prior research targeted applications at or shortly after tuber initiation during the period of known susceptibility, with later treatment providing little or no control. This study examined the effect of a range of application dates and the influence of multiple applications at low and high rates on common scab control in both Russet Burbank and Desiree cultivars. We show that applications as early as 5 days after average plant emergence gave the greater disease control for both cultivars. These early treatments provide sufficient material to the tuber to induce resistance that lasts throughout the tuber susceptibility period with no requirement for, or benefit of repeated applications. Agronomic assessments suggested minor effects on total tuber mass produced with 2,4‐D treatment but these were not consistent. Effective treatments result in levels of 2,4‐D at harvest below the Australian maximum residue limit.
Food security, the labor market, and poverty in the Brazilian bio‐economy
Authors: de Souza Ferreira Filho Joaquim Bento
Published: July 2013

This article deals with the social implications of ethanol expansion in Brazil. The evolution of the labor market in sugarcane production in the country is analyzed together with its regional patterns of expansion, to illustrate how changes in the recent expansion are modifying the traditional pattern of labor demand in the activity. At the same time, the distributional effects of sugarcane expansion, as well as it's impacts on food security and land use change was approached with the aid of general equilibrium simulation models. The analysis shows that both the average earnings and the average years of schooling in sugarcane production are actually higher than in general agriculture in Brazil, and that this is linked to the growing increase in production in the Southeast and Central‐West. Sugarcane production in these regions is more capital intensive and has a much higher productivity than in other traditional regions in Northeast Brazil. The study concludes that the expansion in sugarcane production according to actual patterns does not have a negative effect on poverty, and has only minor impacts on food prices and deforestation. The increase in the regional economic imbalances within the country appears to be the problem that requires attention.
Impediments to applying the ‘dignity of risk’ principle in residential aged care services
Authors: Ibrahim Joseph E , Davis Marie‐Claire
Published: July 2013

This discussion paper identifies four core factors currently impeding the application of the dignity of risk principle in residential aged care settings in Victoria, Australia: the fluctuating decision‐making ability of residents; multiple participants in decision‐making; discordance between espoused values and actions; and confusion and fear around legal responsibilities of care providers. Potential solutions identified include a conceptual shift in approach and consensus between key stakeholders, as well as more tangible solutions such as education and point‐of‐care decision support tools.
The effect of pars plan vitrectomy on oxygen saturation in retinal vessels – a pilot study
Authors: Šín Martin , Šínová Irena , Chrapek Oldřich , Prachařová Zuzana , Karhanová Marta , Langová Kateřina , Řehák Jiři
Published: July 2013

Purpose:  To determine the effect of pars plana vitrectomy (PPV) on oxygen saturation in retinal vessels.

Methods:  We performed a prospective consecutive interventional case series of 20 eyes of 20 patients with macular hole or epiretinal membrane. We performed automatic retinal oximetry (Oxymap Inc., Reykjavik, Iceland) in each patient 24 hr prior to and 45 days (range 42–49) after PPV (classic 20G or sutureless 23G). We analysed oxygen saturations in retinal arteries and veins. Vessel segments of first or second degree were selected. The same segment was analysed before and after PPV. Oximetry data were compared by paired two‐tailed t‐test.

Results:  Pars plana vitrectomy did not alter arterial haemoglobin saturation with oxygen (98 ± 2% prior to the surgery and 98 ± 3% after the procedure, p = 0.549). The mean venous haemoglobin saturation with oxygen increased after vitrectomy from 63 ± 10% to 66 ± 8% (p = 0.012).

Conclusions:  Oxygen saturation is higher in retinal veins after pars plana vitrectomy. Further studies are needed to unveil the mechanism of how vitrectomy affects oxygen metabolism in the retina.
Effect of overnight wear of the Triggerfish® sensor on corneal thickness measured by Visante® anterior segment optical coherence tomography
Authors: Hubanova Ralitsa , Aptel Florent , Chiquet Christophe , Mottet Benjamin , Romanet Jean‐Paul
Published: July 2013

Purpose

To evaluate the effect of overnight wear of the Triggerfish® contact lens sensor (CLS) on central corneal thickness (CCT) using the Visante® anterior segment optical coherence tomography (AS‐OCT).

Methods

Twelve healthy subjects were studied in a sleep laboratory. An ophthalmic examination including ultrasonic CCT, corneal topography, specular microscopy and AS‐OCT CCT was performed. Starting at 7 pm, the Triggerfish® CLS was fitted on one randomly selected eye. Similar AS‐OCT measurements were taken on both eyes every 2 hr from 8 pm to 8 am. The CLS was removed just after the 8 am measurement session. Measurements were repeated at 9 am.

Results

Twenty‐four eyes of 12 subjects were studied (mean age, 22.1 ± 2.4 years; four men/eight women). CCT significantly increased during the night in both CLS and control eyes (p < 0.01). The maximal change was +4.4 ± 1.7% in the CLS eyes and +2.9 ± 1.8% in the control eyes (p < 0.05). Throughout the night, CCT significantly increased more in eyes with CLS than in control eyes (p < 0.05). There were significantly more corneal curvature irregularities after overnight wear of the CLS than in the control eye: +1.63 Dioptre (D) versus −0.02 D in the 3‐mm central zone and +3.17 D versus +0.01 D in the 5‐mm central zone (p < 0.01).

Conclusion

CCT and corneal curvature irregularities increased slightly but significantly more in eyes with the Triggerfish® CLS than in control eyes during overnight wear. Further studies are required to determine whether the corneal curvature changes modify the signal recorded by the sensor.
Medication Counselling: Physicians' Perspective
Authors: Bonnerup Dorthe Krogsgaard , Lisby Marianne , Eskildsen Anette Gjetrup , Sædder Eva Aggerholm , Nielsen Lars Peter
Published: July 2013

Medication reviews have the potential to lower the incidence of prescribing errors. To benefit from a medication review, the prescriber must adhere to medication counselling. Adherence rates vary from 39 to 100%. The aim of this study was to examine counselling‐naive hospital physicians' perspectives and demands to medication counselling as well as study factors that might increase adherence to the counselling. The study was conducted as a questionnaire survey among physicians at Aarhus University Hospital, Denmark. The questionnaire was developed based on focus group interviews and literature search, and was pilot‐tested among 30 physicians before being sent to 669 physicians. The questionnaire consisted of 35 items divided into four categories: attitudes (19 items), behaviours (3 items), assessment (8 items) and demographics (5 items). The response rate was 60% (400/669). Respondents were employed at psychiatric, medical or surgical departments. Eighty‐five per cent of respondents agreed that patients would benefit of an extra medication review, and 72% agreed that there was a need for external medication counselling. The most important factor that could increase adherence was the clinical relevance of the counselling as 78% rated it of major importance. The most favoured method for receiving counselling was via the electronic patient record.
Impact on L‐carnitine Homeostasis of Short‐term Treatment with the Pivalate Prodrug Tenofovir Dipivoxil
Authors: Jia Yan‐Yan , Lu Cheng‐Tao , Feng Juan , Song Ying , Zhao Jin‐Yi , Wang Shan , Sun Yuan , Wen Ai‐Dong , Yang Zhi‐Fu , Hang Tai‐Jun
Published: July 2013

Pivalate‐generating prodrugs have been suggested to cause clinically significant hypocarnitinaemia. Tenofovir dipivoxil, a novel ester prodrug of tenofovir, can be used for treatment for hepatitis B and HIV infection and it was necessary to evaluate the effect of its treatment on carnitine homeostasis. We sought to investigate the effect of Class 1 drug tenofovir dipivoxil on endogenous L‐carnitine level during a 72‐hr test in healthy Chinese volunteers and to establish a suitable dose of L‐carnitine nutritional supplement for patients who were administered short‐term tenofovir dipivoxil tablets for treatment for hepatitis B and herpes simplex virus infection. Tenofovir dipivoxil was administered in one of eight dosing regimens (single dose 150, 300 and 600 mg, multiple dose 300, 450, and 600 mg, multiple dose 450 (600) mg tenofovir dipivoxil and 0.5 g L‐carnitine) to gender‐balanced groups of 84 healthy Chinese volunteers. Plasma concentrations of L‐carnitine were quantified before, during and after treatment. Plasma L‐carnitine concentrations fell during tenofovir dipivoxil dosing. The nadir in L‐carnitine concentration was dependent on the dose of tenofovir dipivoxil and it decreased from 6.1 ± 0.6 to 4.4 ± 0.8 μg/ml, 6.1 ± 1.8 to 3.3 ± 1.2 μg/ml, 6.2 ± 0.6 to 2.5 ± 0.5 μg/ml for single doses of 150, 300, 600 mg tenofovir dipivoxil tablets and from 6.0 ± 1.4 to 2.1 ± 1.5 μg/ml, 6.2 ± 0.4 to 0.9 ± 0.5 μg/ml for multiple doses of 450, 600 mg tenofovir dipivoxil tablets, respectively. Short‐term administration of tenofovir dipivoxil results in hypocarnitinaemia and increased losses of carnitine in resulting of minor adverse events of decreased food appetite, nausea, abdominal distention and muscle weakness.
Modeling bipolar disorder suicidality
Authors: Malhi Gin S , Bargh Danielle M , Kuiper Sandy , Coulston Carissa M , Das Pritha
Published: July 2013

Objectives

To review the psychosocial, neuropsychological, and neurobiological evidence regarding suicide and bipolar disorder (BD), to enable the development of an integrated model that facilitates understanding, and to provide a useful framework for future research.

Methods

A two‐stage literature review was conducted. First, an electronic literature search was performed using key words (e.g., bipolar disorder, suicide risk, and neuroimaging) and standard databases (e.g., MEDLINE). Second, theoretical suicide models were reviewed, and their evidence base and relevance to BD were evaluated in order to determine a guiding theoretical framework for contextualizing suicide in BD.

Results

Although accumulating clinical, cognitive, and neurobiological correlates of suicide have been identified in BD, extant research has been largely atheoretical. The Cry of Pain (CoP) and an adapted version of the model, the Schematic Appraisals Model of Suicide (SAMS), provide a useful schema for examining vulnerability to suicide in BD, by taking into account biopsychosocial determinants of suicidality. In combination, these also provide a model within which the neural correlates of suicide can be integrated.

Conclusions

The proposed Bipolar Suicidality Model (BSM) highlights the psychosocial precursors to suicidality in BD, while recognizing the key role of cognitive deficits and underlying functional neurobiological abnormalities. It usefully integrates our knowledge, and provides a novel perspective that is intended to meaningfully inform future research initiatives, and can lead to a better understanding of suicidality in bipolar disorder. Ultimately, it is hoped that it will facilitate the development of targeted interventions that diminish the risk of suicide in bipolar disorder.
Splanchnic vein thrombosis in myeloproliferative neoplasms
Authors: Sekhar Mallika , McVinnie Kathryn , Burroughs Andrew K.
Published: July 2013

Splanchnic vein thrombosis (SVT) is one of the most important complications of myeloproliferative neoplasms (MPN). Although MPN are common causes of SVT, the pathophysiological mechanisms underlying this predisposition, their epidemiology and natural history are not fully understood. Studies have concentrated on the generalized prothrombotic environment generated by MPN and their relationship with abnormal blood counts, thereby furthering our knowledge of arterial and venous thrombosis in this population. In contrast, there are few studies that have specifically addressed SVT in the context of MPN. Recent research has demonstrated in patients with MPN the existence of factors increasing the risk of SVT such as the presence of the JAK2 V617F mutation and its 46/1 haplotype. Features unique to the circulating blood cells, splanchnic vasculature and surrounding micro‐environment in patients with MPN have been described. There are also abnormalities in local haemodynamics, haemostatic molecules, the spleen, and splanchnic endothelial and endothelial progenitor cells. This review considers these important advances and discusses the contribution of individual anomalies that lead to the development of SVT in both the pre‐neoplastic and overt stage of MPN. Clinical issues relating to epidemiology, recurrence and survival in these patients have also been reviewed and their results discussed.
Enhanced and aberrant T cell trafficking following total body irradiation: a gateway to graft‐versus‐host disease?
Authors: Vianello Fabrizio , Cannella Laura , Coe David , Chai Jian‐Guo , Golshayan Dela , Marelli‐Berg Federica M. , Dazzi Francesco
Published: July 2013

Pre‐transplant conditioning regimens play a major role in triggering graft‐versus‐host disease (GVHD). This study investigated the effect of irradiation on donor T cell trafficking to lymphoid and non‐lymphoid tissues by comparing the migration of carboxy‐fluorescein diacetate succinimidyl ester‐labelled, naïve donor T lymphocytes in vivo in irradiated and non‐irradiated syngeneic mice recipients. Recruitment of adoptively transferred naïve T cells to secondary lymphoid organs was increased in irradiated mice and naïve T cells also aberrantly localized to non‐lymphoid tissues. Irradiation also induced aberrant effector memory T cell migration into lymph nodes and their localization to homing‐privileged non‐lymphoid sites, such as the gut. The presence of a minor histocompatibility mismatch further enhanced the aberrant accumulation of T cells in both lymphoid and non‐lymphoid tissue, whilst their migratory pattern was not modified as compared to fully matched irradiated recipients. These effects correlated with decreased permeability of, and the secretion of chemotactic factors by the endothelium. Our findings are consistent with the possibility that excessive, dysregulated extravasation of T cells induced by irradiation promotes the development of GVHD.
Change in metabolic parameters and weight in response to risperidone monotherapy in young children with nonpsychotic disorders: a prospective open‐label study
Authors: Alan Burcu Ersoz , Cengel Kultur S. Ebru
Published: July 2013

Background

This study investigates changes in metabolic parameters in prepubertal children after 14–16 weeks of treatment with low‐dose risperidone.

Method

Thirty‐one children (mean age 5.46 ± 1.98 years) were treated with risperidone (0.25–1 mg/day; 0.01–0.07 mg/kg/day). Patients were excluded if they were using any medication other than risperidone or were diagnosed with any medical problem in addition to a non‐psychotic disorder.

Results

Weight (Δ: 2.51 ± 1.94 kg), height (Δ: 0.03 ± 0.04 cm), BMI (Δ: 0.82 ± 1.4), BMI percentile (Δ: 9.72 ± 16.40), BMI z‐score (Δ: 0.33 ± 1.03), triglyceride (Δ: 1.50 ± 23.97 mg/dl), very low density lipoprotein (Δ: 2.99 ± 4.76 mg/dl), insulin (Δ: 3.07 ± 3.38 mIU/ml), and leptin (Δ: 3.02 ± 4.69 ng/ml) were significantly increased (p < .05).

Conclusion

The metabolic side effects of risperidone must be carefully monitored in prepubertal children.
Design and Synthesis of Imidazolidine‐2,4‐Dione Derivatives as Selective Inhibitors by Targeting Protein Tyrosine Phosphatase‐1B Over T‐Cell Protein Tyrosine Phosphatase
Authors: Ma Ying , Sun Su‐Xia , Cheng Xian‐Chao , Wang Shu‐Qing , Dong Wei‐Li , Wang Run‐Ling , Xu Wei‐Ren
Published: July 2013

Owing to its special role as a negative regulator in both insulin and leptin signaling, protein tyrosine phosphatase‐1B (PTP1B) has drawn considerable attention as a target for treating type 2 diabetes and obesity. It, however, is a great challenge to discover inhibitors specific to each PTP due to the highly homologous. In this study, a series of compounds were discovered to inhibit PTP1B based on imidazolidine‐2,4‐dione by means of ‘core hopping’. A selective PTP1B inhibitor (comp#h) was identified, and molecular dynamics simulation and binding free energy calculation were carried out to propose the most likely binding mode of comp#h with PTP1B. The findings reported here may provide a new strategy in discovering selective and effective inhibitors for treating diabetes.
Perinatal risk factors for wheezing phenotypes in the first 8 years of life
Authors: Caudri D. , Savenije O. E. M. , Smit H. A. , Postma D. S. , Koppelman G. H. , Wijga A. H. , Kerkhof M. , Gehring U. , Hoekstra M. O. , Brunekreef B. , de Jongste J. C.
Published: July 2013

Background

A novel data‐driven approach was used to identify wheezing phenotypes in pre‐schoolchildren aged 0–8 years, in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort. Five phenotypes were identified: never/infrequent wheeze, transient early wheeze, intermediate onset wheeze, persistent wheeze and late onset wheeze. It is unknown which perinatal risk factors drive development of these phenotypes.

Objective

The objective of the study was to assess associations of perinatal factors with wheezing phenotypes and to identify possible targets for prevention.

Methods

In the PIAMA study (n = 3963), perinatal factors were collected at 3 months, and wheezing was assessed annually until the age of 8 years. Associations between perinatal risk factors and the five wheezing phenotypes were assessed using weighted multinomial logistic regression models. Odds ratios were adjusted for confounding variables and calculated with ‘never/infrequent wheeze’ as reference category.

Results

Complete data were available for 2728 children. Risk factors for transient early wheeze (n = 455) were male gender, maternal and paternal allergy, low maternal age, high maternal body mass index, short pregnancy duration, smoking during pregnancy, presence of older siblings and day‐care attendance. Risk factors for persistent wheeze (n = 83) were male gender, maternal and paternal allergy, and not receiving breastfeeding for at least 12 weeks. Intermediate onset wheeze (n = 98) was associated with a lower birth weight and late onset wheeze (n = 45) with maternal allergy.

Conclusion and Clinical Relevance

We identified different risk factors for specific childhood wheezing phenotypes. Some of these are modifiable, such as maternal age and body mass index, smoking, day‐care attendance and breastfeeding, and may be important targets for prevention programmes.
A long‐term follow‐up study of eighteen patients with thyrotrophin‐secreting pituitary adenomas
Authors: van Varsseveld Nadège C. , Bisschop Peter H. L. T. , Biermasz Nienke R. , Pereira Alberto M. , Fliers Eric , Drent Madeleine L.
Published: July 2013

Objective

TSH‐secreting pituitary adenomas (TSH‐omas) are a rare cause of thyrotoxicosis. First‐line therapy for these tumours is neurosurgery, although medical therapy with somatostatin analogues (SSAs) is increasingly used for this indication.

Design and patients

We retrospectively reviewed the data of patients with a TSH‐oma (n = 18, 67% males) followed between 1989 and 2011 (median follow‐up 7 years, range 1–21) in three academic medical centres in the Netherlands, focusing on the role of SSA treatment.

Measurements

Patient records were reviewed for clinical, biochemical, imaging, pathological and treatment characteristics.

Results

At initial evaluation, biochemical hyperthyroidism with non‐suppressed TSH concentrations was detected in 94% of the patients. The majority of patients (72%) had a macroadenoma with extrasellar extension. Fourteen patients underwent surgery, resulting in postoperative euthyroidism in six patients (43%). Recurrence of hyperthyroidism developed in three of them after 5, 24 and 32 months, respectively. Adjuvant radiotherapy (n = 2) did not induce remission. Three patients received SSA therapy exclusively, resulting in apparent cure in one of them. During long‐term follow‐up, 72% of all patients required medical therapy (mostly SSA treatment). Euthyroidism was achieved in all but one patient, who refused all treatments.

Conclusions

Our results demonstrate that patients with TSH‐omas, who often present with large macroadenomas with extrasellar extension, have an excellent response to SSA therapy. Because the results of surgery and radiotherapy are disappointing, primary medical therapy may be considered in virtually all patients, except in case of optic chiasm compression, especially in those harbouring large adenomas with parasellar extension.
No remarkable differences in rates of sensitization to common type I and IV allergens between FLG loss‐of‐function mutation carriers and wild‐type subjects
Authors: Landeck Lilla , Visser Maaike , Skudlik Christoph , Brans Richard , Kezic Sanja , John Swen Malte
Published: July 2013

Background

Loss‐of‐function mutations in the filaggrin gene (FLG) have been associated with reduced skin barrier function, possibly allowing increased penetration of irritants and allergens.

Objectives

To study whether FLG loss‐of‐function mutation carriers show different rates of sensitization to common type I and IV allergens among patients referred for occupational contact dermatitis of the hands.

Materials and Methods

Four hundred and ninety‐six Caucasian patients were genotyped for four FLG null mutations and patch tested with the European baseline series. In addition, 431 patients underwent prick testing with common type I allergens.

Results

Overall, 67 patients showed a heterozygous mutation in the FLG alleles R501X, R2447X, S3247X, and/or 2282del4. Sensitization rates for type I allergens from a European prick test series did not show significant differences between FLG loss‐of‐function mutation carriers and wild‐type subjects. For type IV allergens, significantly more FLG loss‐of‐function carriers were found to be sensitized to lanolin and p‐tert‐butylphenol‐formaldehyde resin.

Conclusions

Probably a variety of immunological mechanisms other than that resulting from the filaggrin system have an impact on allergic sensitization to a greater degree. Larger cohorts may be necessary to increase the statistical power of the findings presented regarding type I and IV sensitization.
The cobalt spot test – further insights into its performance and use
Authors: Midander Klara , Julander Anneli , Skare Lizbet , Thyssen Jacob P. , Lidén Carola
Published: July 2013

Background

A spot test was recently developed for easy and rapid testing to detect whether cobalt is available on surfaces in contact with skin.

Objectives

To explore the potential use of the cobalt spot test as a tool for skin dose assessment, and to verify the sensitivity under laboratory conditions.

Methods

A cobalt dilution series (cobalt standards mixed with cobalt spot test reagent solution) was prepared to determine the threshold for colour change. Defined doses of cobalt were applied to the fingers of 5 volunteers. Acid wipe sampling was used to measure the recovery of applied cobalt skin doses on one hand, and cobalt‐exposed areas on the other hand were spot tested.

Results

A weak colour gradient was visible from approximately 1 to 1.5 µg cobalt/ml in the dilution series. For a skin dose of 0.125 µg cobalt/cm2, 80% of the cobalt dose was collected by acid wipe sampling. Spot tests gave positive results in all cases (n = 5).

Conclusions

The cobalt spot test can be used to show cobalt on the skin. More experience is needed to understand and describe the most suitable test conditions.
What can be learnt from nothing? – A statistical perspective
Authors: Gefeller Olaf , Pfahlberg Annette B. , Uter Wolfgang
Published: July 2013

Background

No observed event is a special, but not uncommon, result in patch test studies. The interpretation of such findings depends critically on the sample size (n) of the investigation, and is statistically addressed by the use of confidence intervals (CIs).

Objective

To define the statistically correct method of calculating a CI with a confidence level of 1 − α, where α denotes the tolerated statistical error probability, for an observed prevalence of 0%.

Methods

A literature survey and evaluation of the statistical methods was conducted. The popular statistical software packages spss™ and sas™ were examined with regard to the methods implemented, and the results obtained, for estimating such CIs in this special case.

Results

The evaluation identified [0; 1 − α1/n], which is well approximated by [0; 3/n] for α = 0.05, as an appropriate method to compute a CI with a confidence level of 1 − α. The resulting CI is an exact one, and more efficient than standard solutions. Popular statistical software such as spss™ and sas™ offers only various inefficient or even invalid procedures, but does not include this method.

Conclusions

It is easy to calculate a CI for an observed prevalence of 0% obtained in some studies. Such a CI facilitates the interpretation of such a finding, as it puts the observed zero result into adequate statistical perspective.
Prognostic value of pretreatment level of carcinoembryonic antigen on tumour downstaging and early occurring metastasis in locally advanced rectal cancer following neoadjuvant radiotherapy (30 Gy in 10 fractions)
Authors: Wang L. , Zhong X.‐G. , Peng Y.‐F. , Li Z.‐W. , Gu J.
Published: July 2013

Aim

To evaluate the role of carcinoembryonic antigen (CEA) in predicting the response to and prognosis for locally advanced rectal cancer treated with 30 Gy neoadjuvant radiotherapy (nRT) in 10 fractions (30 Gy/10 f).

Method

This retrospective study involved 240 patients with locally advanced rectal cancer who underwent 30 Gy/10 f nRT (biologically equivalent dose 36 Gy) followed by total mesorectal excision between August 2003 and 2009. Serum CEA level was determined before administration of nRT. The prognostic value of serum CEA level on tumour downstaging and 3‐year disease‐free survival was analysed.

Results

Ninety out of 240 (37.5%) patients had elevated CEA levels before nRT. The incidence of T downstaging in patients decreased significantly as the pretreatment CEA levels became more elevated (< 5 ng/ml, 50.7%; 5–10 ng/ml, 39.5%; > 10 ng/ml, 17.3%; P = 0.00014). Downstaging to ypCR or ypStage I occurred in 46.7% (66/150) of patients with a CEA level of < 5 ng/ml and 34.2% (13/38) of patients with a CEA level of 5–10 ng/ml. In contrast, just 13.5% (7/52) of those with a CEA level > 10 ng/ml downstaged to ypStage I and none of them achieved ypCR, with statistical difference (P = 0.001). A significantly higher incidence of early metastasis (within 6 postoperative months) was observed with increasing CEA level: 2.0% (3/150), 5.4% (2/38) and 11.5% (6/52) in patients with CEA level < 5 ng/ml, 5–10 ng/ml or > 10 ng/ml, respectively (P = 0.018).

Conclusion

Pretreatment CEA level cannot only predict tumour downstaging and ypTNM stage for rectal cancer following 30 Gy/10 f nRT, but also promisingly suggests a high incidence of early occurring distant metastasis. These findings may be used to select patients with nRT resistance and occult metastasis and make alternative treatment strategies.
Working Memory in Nonsymbolic Approximate Arithmetic Processing: A Dual‐Task Study With Preschoolers
Authors: Xenidou‐Dervou Iro , van Lieshout Ernest C. D. M. , van der Schoot Menno
Published: July 2013

Preschool children have been proven to possess nonsymbolic approximate arithmetic skills before learning how to manipulate symbolic math and thus before any formal math instruction. It has been assumed that nonsymbolic approximate math tasks necessitate the allocation of Working Memory (WM) resources. WM has been consistently shown to be an important predictor of children's math development and achievement. The aim of our study was to uncover the specific role of WM in nonsymbolic approximate math. For this purpose, we conducted a dual‐task study with preschoolers with active phonological, visual, spatial, and central executive interference during the completion of a nonsymbolic approximate addition dot task. With regard to the role of WM, we found a clear performance breakdown in the central executive interference condition. Our findings provide insight into the underlying cognitive processes involved in storing and manipulating nonsymbolic approximate numerosities during early arithmetic.
Stepping Into a Map: Initial Heading Direction Influences Spatial Memory Flexibility
Authors: Gagnon Stephanie A. , Brunyé Tad T. , Gardony Aaron , Noordzij Matthijs L. , Mahoney Caroline R. , Taylor Holly A.
Published: July 2013

Learning a novel environment involves integrating first‐person perceptual and motoric experiences with developing knowledge about the overall structure of the surroundings. The present experiments provide insights into the parallel development of these egocentric and allocentric memories by intentionally conflicting body‐ and world‐centered frames of reference during learning, and measuring outcomes via online and offline measures. Results of two experiments demonstrate faster learning and increased memory flexibility following route perspective reading (Experiment 1) and virtual navigation (Experiment 2) when participants begin exploring the environment on a northward (vs. any other direction) allocentric heading. We suggest that learning advantages due to aligning body‐centered (left/right/forward/back) with world‐centered (NSEW) reference frames are indicative of three features of spatial memory development and representation. First, memories for egocentric and allocentric information develop in parallel during novel environment learning. Second, cognitive maps have a preferred orientation relative to world‐centered coordinates. Finally, this preferred orientation corresponds to traditional orientation of physical maps (i.e., north is upward), suggesting strong associations between daily perceptual and motor experiences and the manner in which we preferentially represent spatial knowledge.
Cat Got Your Tongue? Using the Tip‐of‐the‐Tongue State to Investigate Fixed Expressions
Authors: Nordmann Emily , Cleland Alexandra A. , Bull Rebecca
Published: July 2013

Despite the fact that they play a prominent role in everyday speech, the representation and processing of fixed expressions during language production is poorly understood. Here, we report a study investigating the processes underlying fixed expression production. “Tip‐of‐the‐tongue” (TOT) states were elicited for well‐known idioms (e.g., hit the nail on the head) and participants were asked to report any information they could regarding the content of the phrase. Participants were able to correctly report individual words for idioms that they could not produce. In addition, participants produced both figurative (e.g., pretty for easy on the eye) and literal errors (e.g., hammer for hit the nail on the head) when in a TOT state, suggesting that both figurative and literal meanings are active during production. There was no effect of semantic decomposability on overall TOT incidence; however, participants recalled a greater proportion of words for decomposable rather than non‐decomposable idioms. This finding suggests there may be differences in how decomposable and non‐decomposable idioms are retrieved during production.