bluuebunny/crossref_metadata_2025 huggingface dataset:
Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin
Authors: Furumai Ryohei , Komatsu Yasuhiko , Nishino Norikazu , Khochbin Saadi , Yoshida Minoru , Horinouchi Sueharu
Published: July 2012

Trichostatin A (TSA) and trapoxin (TPX) are potent inhibitors of
histone deacetylases (HDACs). TSA is proposed to block the catalytic
reaction by chelating a zinc ion in the active-site pocket through its
hydroxamic acid group. On the other hand, the epoxyketone is
suggested to be the functional group of TPX capable of alkylating the
enzyme. We synthesized a novel TPX analogue containing a hydroxamic
acid instead of the epoxyketone. The hybrid compound cyclic hydroxamic
acid-containing peptide (CHAP) 1 inhibited HDAC1 at low nanomolar
concentrations. The HDAC1 inhibition by CHAP1 was reversible as it was
by TSA, in contrast to the irreversible inhibition by TPX. CHAP with an
aliphatic chain length of five, which corresponded to that of
acetylated lysine, was stronger than those with other lengths. These
results suggest that TPX is a substrate mimic and that the replacement
of the epoxyketone with the hydroxamic acid converted TPX to an
inhibitor chelating the zinc like TSA. Interestingly, HDAC6, but not
HDAC1 or HDAC4, was resistant to TPX and CHAP1, whereas TSA inhibited
these HDACs to a similar extent. HDAC6 inhibition by TPX at a high
concentration was reversible, probably because HDAC6 is not alkylated
by TPX. We further synthesized the counterparts of all known naturally
occurring cyclic tetrapeptides containing the epoxyketone. HDAC1 was
highly sensitive to all these CHAPs much more than HDAC6, indicating
that the structure of the cyclic tetrapeptide framework affects the
target enzyme specificity. These results suggest that CHAP is a unique
lead to develop isoform-specific HDAC inhibitors.
Constitutive arrestin-mediated desensitization of a human vasopressin receptor mutant associated with nephrogenic diabetes insipidus
Authors: Barak Larry S. , Oakley Robert H. , Laporte Stéphane A. , Caron Marc G.
Published: July 2012

Agonist-dependent desensitization and internalization of G
protein-coupled receptors (GPCR) are mediated by the binding of
arrestins to phosphorylated receptors. The affinity of arrestins for
the phosphorylated GPCR regulates the ability of the internalized
receptor to be dephosphorylated and recycled back to the plasma
membrane. In this study, we show that the naturally occurring loss
of function vasopressin receptor mutation R137H, which is associated
with familial nephrogenic diabetes insipidus, induces constitutive
arrestin-mediated desensitization. In contrast to the wild-type
vasopressin receptor, the nonsignaling R137H receptor is phosphorylated
and sequestered in arrestin-associated intracellular vesicles even in
the absence of agonist. Eliminating molecular determinants on the
receptor that promote high affinity arrestin–receptor interaction
reestablishes plasma membrane localization and the ability of the
mutated receptors to signal. These findings suggest that unregulated
desensitization can contribute to the etiology of a GPCR-based disease,
implying that pharmacological targeting of GPCR desensitization may be
therapeutically beneficial.
Contrasted and maintained information in a narrative task
Authors: Giuliano Patrizia
Published: July 2012

This paper proposes an analysis of 100 narrative texts concerned with English and Italian as L1s and L2s. We will compare the way both native speakers and learners build textual cohesion when faced with a narrative task involving several referential restrictions: contrasts of entity and polarity, maintenance of the same predication, temporal shifts etc. The stimulus used to collect the data is the film retelling The Finite Story by Dimroth (2006). Our results will add to the debate about the learners’ tendency to establish anaphoric linkage according to the specific grammaticised (readily encodable) concepts of their mother tongue. In particular, we will show that even at very advanced and almost native levels learners tend to exploit formal and conceptual means resembling those of their mother tongue, demonstrating by that that they have not completely abandoned the L1 specific “perspective taking”.
Pragmatic development in Chinese speakers’ L2 English refusals
Authors: Ren Wei
Published: July 2012

This study investigates the effect of learning environment (study abroad vs. at home) on the pragmatic development of Chinese speakers’ L2 English refusals. A total of 20 Chinese Study Abroad (SA) students participated in the study and their L2 refusals were examined over the course of one academic year. These refusals were compared with those of 20 Chinese At Home (AH) students. Data were collected three times by an 8-situation Multimedia Elicitation Task. The results revealed that the SA students’ overall frequency of opt-outs remained consistent throughout a year’s stay in the L2 community but the study abroad experience influenced their choices sociopragmatically. Regarding repertoire of refusal strategies and that of refusal adjuncts, both groups demonstrated significant development, thus indicating no significant benefit of study abroad in these respects. The findings reveal the complexity of L2 pragmatic development and the importance of longitudinal investigations in such research.
On the relationship between sociolinguistic and grammatical development
Authors: Howard Martin
Published: July 2012

While SLA studies on the acquisition of sociolinguistic variation have primarily illuminated the impact of social and socio-biographic factors on such development, this paper is a response to the need for studies of the relationship between sociolinguistic development and other components of the learner’s L2 linguistic repertoire, such as grammatical development, which is the focus of this study. With the aim of exploring the hypothesis that grammatical development is a pre-requisite to sociolinguistic development, the study presents quantitative findings which compare longitudinal development on a number of grammatical and sociolinguistic features in the case of Irish university learners of French. Findings suggest that while grammatical development may be important, it may be not enough, such that it is naturalistic exposure which provides the necessary impetus for such sociolinguistic development. Moreover, the extent of grammatical development in terms of the range of grammatical features which are productively used within the learner’s linguistic repertoire is a further factor which complexifies the issue.
Personality and L2 use
Authors: Ożańska-Ponikwia Katarzyna , Dewaele Jean-Marc
Published: July 2012

Researchers working on the effects of study abroad are always baffled by the huge individual differences in the development of a target language (TL) among students – who could be considered as temporary immigrants (Kinginger 2011; Regan et al. 2009). Researchers often speculate that these differences are linked to socialization issues, such as the amount of authentic TL interactions that students engage in. What research designs usually lack are the unique psychological characteristics that could predict the frequency with which L2 users’ engage in L2 interactions. The present study investigates this question by looking at the link between personality traits and frequency of use of English L2 as well as self-perceived proficiency in English L2 by 102 adult Polish immigrants living in Ireland and the UK. Participants filled out a Polish version of personality questionnaires (OCEAN and TEIQ) and a sociobiographical questionnaire. Statistical analyses revealed that length of stay was positively correlated with English L2 use and self-perceived proficiency in that language. Linear regression analyses revealed that Openness and Self-esteem were significant predictors of frequency of use of English L2. Openness was the best predictor of self-perceived English L2 proficiency. In sum, our results suggest that progress in the L2 depends not just on the immersion in the L2 but also on the L2 user’s basic inclination to seek out social interactions in the L2.
On Theme as a grammatical notion for German
Authors: Steiner Erich , Ramm Wiebke
Published: July 2012

We outline an approach to Theme as a grammatical notion for German. Our starting point is some earlier accounts of Theme in the framework of Systemic Functional Linguistics. These are followed by a consideration of some representational requirements for a treatment of Theme in German. We then suggest an initial account of grammatical Theme in German, followed by some questions relating to historical, typological, and functional explanations of differences observed between English and German.
Standardising Cornish
Authors: Sayers Dave
Published: July 2012

The last recorded native speaker of the Cornish language died in 1777. Since the nineteenth century, amateur scholars have made separate attempts to reconstruct its written remains, each creating a different orthography. Later, following recognition under the European Charter for Regional or Minority Languages in 2002, Cornish gained new status. However, with government support came the governmental framework of “New Public Management”, which emphasises quantifiable outcomes to measure performance. This built implicit pressure towards finding a single standard orthography, for greatest efficiency. There followed a six-year debate among supporters of the different orthographies, usually quite heated, about which should prevail. This debate exemplified the importance of standardisation for minority languages, but its ultimate conclusion saw all sides giving way, and expediency, not ideology, prevailing. It also showed that standardisation was not imposed explicitly within language policy, but emerged during the language planning process.
Official English in the constitutions and statutes of the fifty states in the United States
Authors: Faingold Eduardo D.
Published: July 2012

The constitutions and legislative statutes of the fifty states in the United States are given an exhaustive screening to identify legal language defining the linguistic obligations of the state and the language rights of individuals and groups. The author suggests that in the United States, “hands-off” is good language policy not only nationwide but also statewide because states adopting a hands-off linguistic policy are consistent with the Constitution of the United States while states adopting a “hands-on” policy are in conflict with it. States adopting hands-on language legislation in their constitutions or statutes are deemed to be “nativist” because they seem unfavorable toward speakers of minority languages, while states adopting a hands-off policy are “non-nativist” because they seem favorable (or at least neutral) toward speakers of minority languages.
Officialization and linguistic acculturation of Spanish in the United States Catholic Church
Authors: Medina-Rivera Antonio
Published: July 2012

The present investigation brings to light some of the changes associated with the use of English and Spanish in the US Catholic Church. The first part is an examination of the process of officialization from a historical perspective, acknowledging the impact of some groups or associations in the use of vernacular languages within the Church. The second part examines the role of acculturation during this process of officialization; and the final section analyzes the use of inclusive language in the Church, as an attempt to have a more gender-balanced institution. These three elements serve to provide a more complete perspective of the reality, expansion, revitalization and maintenance of the Spanish language in the United States. The article also reveals some of the language planning policies (direct and indirect) that have made an impact on the use of Spanish within US Catholicism.
Exploring literary translation practice
Authors: Flynn Peter
Published: July 2012

This article discusses findings from an ethnographic study of literary translation practice in the Netherlands and Belgium. The article focuses on one aspect of translation practice, namely translatorial ethos. It is argued that the forms of translatorial ethos visible in the data are complex in that they have a bearing both on textual and institutional practice and relations at one and the same time. More specifically, it is also argued that these complex professional stances and positionings need to be taken into account if we are to gain a better understanding of translational norms (Toury 1995, 2000andChesterman 1993) or translational habitus (Simeoni 1998). Furthermore, it is argued in a more general sense that linguistic ethnography can provide clear indications of patterns of translational practice and therefore forms a useful means of inquiry in the context of translation studies.
Evidence for Parr Growth as a Factor Affecting Parr‐to‐Smolt Survival
Authors: Connor William P. , Tiffan Kenneth F.
Published: July 2012

Data collected on juvenile anadromous salmonids implanted with passive integrated transponder (PIT) tags are used in mark–recapture analyses to understand the factors affecting survival of fish estimated between rearing in riverine habitat and dam passage. We estimated parr‐to‐smolt survival of PIT‐tagged naturally produced subyearling fall Chinook salmon Oncorhynchus tshawytscha to examine the previously unexplored influences of environmental and biological conditions measured prior to reservoir entry. Mean (±SE) parr‐to‐smolt survival of the early migrating cohorts was 45.4 ± 6.3% (n = 13) compared with 37.4 ± 4.7% (n = 13) for later migrating cohorts. Annual mean parr‐to‐smolt survival differed widely across years ranging from a low of 9.6 ± 0.5% (n = 2) in 2001 to a high of 81.7 ± 4.6% (n = 2) in 1999. Parr growth prior to reservoir entry and reservoir velocity provided the most information on variability in parr‐to‐smolt survival (N = 26, R2 = 0.75, corrected Akaike's information criterion [AICc] = −5.01). We suggest that parr growth and reservoir velocity were directly proportional to parr‐to‐smolt survival because fast growth and downstream movement reduces the time when fish are vulnerable to predators. The effect of reservoir velocity comports with previous published studies and supports management efforts to increase reservoir velocity. Few if any published studies explicitly relate parr growth measured on individual fish to survival estimated for their cohorts in freshwater. This study provides empirical evidence that upholds the long‐held belief that any anthropogenic activity that reduces growth of juvenile salmonids during freshwater rearing has the potential to reduce their survival.
Survival and Growth of Juvenile Pacific Lampreys Tagged with Passive Integrated Transponders (PIT) in Freshwater and Seawater
Authors: Mesa Matthew G. , Copeland Elizabeth S. , Christiansen Helena E. , Gregg Jacob L. , Roon Sean R. , Hershberger Paul K.
Published: July 2012

Tagging methods are needed for both adult and juvenile life stages of Pacific lampreys Lampetra tridentata to better understand their biology and factors contributing to their decline. We developed a safe and efficient technique for tagging juvenile Pacific lampreys with passive integrated transponder (PIT) tags. We tested the short‐term survival of PIT‐tagged juvenile lampreys in freshwater at four temperatures (9, 12, 15, and 18°C) and their long‐term growth and survival in seawater. For both experiments there was little to no tag loss, and juvenile lampreys in freshwater showed high survival at all temperatures at 7 d (95–100%) and 14 d (88–100%) posttagging. Prolonged holding (40 d) resulted in significantly lower survival (28–79%) at warmer temperatures (12–18°C). For juvenile lampreys tagged in freshwater and then transitioned to seawater, survival was 97% for tagged fish until day 94, and at the end of 6 months, survival was about 58% for both tagged and control fish. About half of the tagged and control fish that survived in seawater grew, but there was no difference in growth between the two groups. In freshwater, but not in seawater, most fish that died had an aquatic fungal infection. In both experiments, survival increased with increasing fish length at tagging. Our results indicate that tags similar in size to a 9‐mm PIT tag are a feasible option for tagging metamorphosed juvenile lampreys migrating downstream and that when fungal infections are mitigated—as in seawater—long‐term (at least 6 months) survival of tagged juvenile lampreys is high.
Swimming Depth, Behavior, and Survival of Atlantic Salmon Postsmolts in Penobscot Bay, Maine
Authors: Renkawitz Mark D. , Sheehan Timothy F. , Goulette Graham S.
Published: July 2012

To gain information on postsmolt dynamics of emigrating Atlantic salmon Salmo salar through Penobscot Estuary and Penobscot Bay, Maine, we conducted a telemetry experiment in 2005. We implanted 26 salmon smolts with ultrasonic depth tags, and monitored movement activity and fish passage with linear detection arrays through 44.2 km of the estuary and 45.5 km of the bay. During daylight in the bay, greater than 95% of the detections occurred in water depths of 5 m or less, but depths to 37 m were recorded. At night, 99% of the detections were in the top 5 m of the water column and maximum depth was 9 m. Overall survival was 39% and was highest for smaller fish and those released earlier in the smolt run, when river discharge was greater. Rapid emigration (i.e., approximately 1 km/h) and preferential surface orientation improved survival. These results verify that postsmolts are primarily surface oriented in the waters of Penobscot Bay and that they may experience high rates of nearshore mortality despite their short residence time. Detailed emigration and behavioral data such as these allow scientists and managers to delineate areas of high mortality to develop strategies that improve survival, and provide marine spatial planners information to minimize impacts of coastal zone development.
Use of Radiotelemetry and Direct Observations to Evaluate Sea Lion Predation on Adult Pacific Salmonids at Bonneville Dam
Authors: Keefer Matthew L. , Stansell Robert J. , Tackley Sean C. , Nagy William T. , Gibbons Karrie M. , Peery Christopher A. , Caudill Christopher C.
Published: July 2012

Management of protected species becomes increasingly complex when one protected population negatively affects another. This occurs along coastlines and in rivers and estuaries of the U.S. Pacific Northwest, where protected marine mammals prey on threatened and endangered Pacific salmonids Oncorhynchus spp. Over 9 years, we observed a growing aggregation of California sea lions Zalophus californianus and Steller sea lions Eumetopias jubatus preying upon adult Chinook salmon O. tshawytscha and steelhead O. mykiss at Bonneville Dam on the Columbia River. Both before and concurrent with the observation study, we monitored radio‐tagged salmon at Bonneville Dam and during their upriver spawning migrations. Springtime sea lion abundance steadily increased from 2002 to 2010 and the aggregation formed earlier each winter. The principal prey species in winter were resident white sturgeon Acipenser transmontanus and migratory steelhead and then shifted to predominantly Chinook salmon when the spring run arrived. Observation‐based estimates of salmonid consumption from January to May varied 12‐fold among years (0.4–4.9%, mean = 2.6% of adult salmonids counted at the dam), and radiotelemetry results corroborated these estimates. The highest proportional impact was in winter and early spring. As salmonid abundance increased, per capita consumption by sea lions increased (Type II functional response) but individual salmonid risk decreased (due to prey swamping). Population‐specific risk analyses indicated predation was substantially higher for early‐timed than for late‐timed salmon populations. The most at‐risk group included Snake River and upper Columbia River Chinook salmon listed as threatened under the U.S. Endangered Species Act. These predation indices should help managers simultaneously tasked with salmon recovery and marine mammal management.
Largemouth Bass Selected for Differential Vulnerability to Angling Exhibit Similar Routine Locomotory Activity in Experimental Ponds
Authors: Binder Thomas R. , Nannini Michael A. , Wahl David H. , Arlinghaus Robert , Klefoth Thomas , Philipp David P. , Cooke Steven J.
Published: July 2012

A growing body of work is focused on attempting to understand the biological mechanism(s) by which some fish are highly vulnerable to angling while others are not. We used electromyogram telemetry to monitor routine locomotory activity of artificially selected largemouth bass Micropterus salmoides in experimental ponds to test two potential explanatory hypotheses: (1) that the difference in angling vulnerability between high‐vulnerability (HV) bass and low‐vulnerability (LV) bass is related to a difference in routine activity level between the two groups, and (2) that the difference in vulnerability between HV and LV bass is related to a difference in the diel activity pattern displayed by each group (e.g., LV fish are more active at night, a time where there is typically little bass fishing effort). Neither hypothesis was supported by our results. Differences in vulnerability to angling in artificially selected lines of largemouth bass were not related to inherent differences in routine locomotory activity in our ponds. Mean daily activity levels were close to 5% of maximum swim speed in both groups, which we estimated to reflect a mean swimming distance of approximately 5,875 m (range = 1,280–9,670 m) per day. There was also no difference in the diel pattern of activity displayed by the two groups. Both HV and LV bass displayed a significant diurnal activity pattern: 16% and 19% higher activity levels during the day than at night, respectively. These results contribute to the ongoing efforts to understand the behavioral basis of vulnerability to angling in largemouth bas and other fish species.
Self-renewal of thymocytes in the absence of competitive precursor replenishment
Authors: Boehm Thomas
Published: July 2012

Soon after transplantation of wild-type thymi into immunodeficient mice lacking functional T cell receptors, productive T cell development in the donor thymus ceases. This observation underlies one of the central dogmas of T cell biology: because thymocytes are seemingly short-lived, intrathymic T cell development depends on continuous import of lymphoid progenitors from the bone marrow. New work reinterprets the outcome of this classical experiment as being the result of competition for intrathymic niches specifically supporting the DN3 stage of early T cell development. Surprisingly, when this niche space is uncontested by immigrating host progenitors, development of T cells in the thymus grafts continues. These new findings suggest that early thymocytes do indeed have substantial self-renewing potential.
A simple guide to biochemical approaches for analyzing protein–lipid interactions
Authors: Zhao Hongxia , Lappalainen Pekka
Published: July 2012

Eukaryotic cells contain many different membrane compartments with characteristic shapes, lipid compositions, and dynamics. A large fraction of cytoplasmic proteins associate with these membrane compartments. Such protein–lipid interactions, which regulate the subcellular localizations and activities of peripheral membrane proteins, are fundamentally important for a variety of cell biological processes ranging from cytoskeletal dynamics and membrane trafficking to intracellular signaling. Reciprocally, many membrane-associated proteins can modulate the shape, lipid composition, and dynamics of cellular membranes. Determining the exact mechanisms by which these proteins interact with membranes will be essential to understanding their biological functions. In this Technical Perspective, we provide a brief introduction to selected biochemical methods that can be applied to study protein–lipid interactions. We also discuss how important it is to choose proper lipid composition, type of model membrane, and biochemical assay to obtain reliable and informative data from the lipid-interaction mechanism of a protein of interest.
First Report of Tobacco rattle virus Associated with Ring Spot and Line Pattern Disease of Peony in Ohio
Authors: Fisher John R.
Published: July 2012

Tobacco rattle virus (TRV) is the type member of the Tobravirus genus which also includes pea early browning and pepper ringspot viruses. The ring spot disease of peony associated with TRV has been reported in Europe and Asia and recently in Alaska but the literature is sparse regarding reports of the disease in the US. These results represent the first confirmed report of TRV in peony in Ohio, and expand the known geographic distribution of the virus.

Accepted for publication 26 June 2012. Published 11 July 2012.
Effects of Temperature and Wetness Duration on the Sporulation of Phomopsis viticola on Infected Grape Canes
Authors: Anco Daniel J. , Madden Laurence V. , Ellis Michael A.
Published: July 2012

In 2008, research was initiated to examine effects of temperature and wetness duration on the sporulation of Phomopsis viticola on infected grape canes and to determine effects of interrupted wetness duration on sporulation. To determine effects of temperature (T) and wetness duration (WD) on sporulation, a split-plot experimental design was used, with T (5, 12, 15, 18, 20, 22, 25, 28, and 35°C) assigned to whole-plots and WD (11, 23, 35, 47, and 71 h) assigned to sub-plots. Linear and nonlinear mixed models were fitted to the data. Lower and upper limits of sporulation were found to be at 5 and 35°C, respectively. Optimum sporulation was near 22°C, and sporulation increased with increasing WD. Of the examined models, a generalized Analytis Beta model fit the data best. To determine effects of wetness interruption (IWD), a split-plot was used, with T (12, 15, and 20°C) assigned to whole-plots and IWD (0, 2, 4, 8, 12, and 24 h) assigned to sub-plots. Generally, sporulation declined with increasing IWD. An IWD of 12 h or more resulted in significantly and substantially less sporulation compared to the control (0 h IWD). Using a repeated-measures design, spore density and environmental data were measured in the vineyard during and following individual rain events; a preliminary model predicted the temporal trend in spore density within the vineyard fairly well (R2 = 0.719), although absolute magnitude of sporulation could not be predicted.

Accepted for publication 27 April 2012. Published 23 July 2012.
An Epidemiological Comparison of the US and Canadian Plum pox virus Eradication Programs
Authors: Gougherty A. V. , Nutter F. W.
Published: July 2012

Plum pox virus (PPV) was first detected in North America in 1999 in Pennsylvania, and the following year in Ontario, Canada. In response to these outbreaks, both countries implemented eradications programs in an effort to eradicate the virus before it could have a significant effect on the Prunus industry in their respective countries. The objectives of this study were to: (i) quantify the impact of the US and Canadian PPV eradication programs on the spatial and temporal dynamics of PPV in Pennsylvania and Ontario; and (ii) compare the detection efficiencies of the US and Canadian PPV sampling systems. Ripley's K function revealed PPV-positive Prunus blocks in Pennsylvania to be clustered between distances of 0.7 and 4.3 km in 2000, while in Ontario, PPV-positive blocks were clustered between distances of 1 and 25 km over the period 2006-2009. A simulation model was developed to determine the relative detection efficiencies of the US and Canadian PPV eradication programs. The US eradication program was found to have a detection efficiency of 71.7%, whereas the Canadian eradication program had a detection efficiency of 40.5%. The data generated in this study should help to improve the PPV eradication programs currently used in the US and Canada, as well as provide a scientific basis to evaluate future eradication programs.

Accepted for publication 23 May 2012. Published 23 July 2012.
High‐resolution behavioral economic analysis of cigarette demand to inform tax policy
Authors: MacKillop James , Few Lauren R. , Murphy James G. , Wier Lauren M. , Acker John , Murphy Cara , Stojek Monika , Carrigan Maureen , Chaloupka Frank
Published: July 2012

Aims

Novel methods in behavioral economics permit the systematic assessment of the relationship between cigarette consumption and price. Towards informing tax policy, the goals of this study were to conduct a high‐resolution analysis of cigarette demand in a large sample of adult smokers and to use the data to estimate the effects of tax increases in 10 US States.

Design

In‐person descriptive survey assessment.

Setting

Academic departments at three universities.

Participants

Adult daily smokers (i.e. more than five cigarettes/day; 18+ years old; ≥8th grade education); n = 1056.

Measurements

Estimated cigarette demand, demographics, expired carbon monoxide.

Findings

The cigarette demand curve exhibited highly variable levels of price sensitivity, especially in the form of ‘left‐digit effects’ (i.e. very high price sensitivity as pack prices transitioned from one whole number to the next; e.g. $5.80–6/pack). A $1 tax increase in the 10 states was projected to reduce the economic burden of smoking by an average of $530.6 million (range: $93.6–976.5 million) and increase gross tax revenue by an average of 162% (range: 114–247%).

Conclusions

Tobacco price sensitivity is non‐linear across the demand curve and in particular for pack‐level left‐digit price transitions. Tax increases in US states with similar price and tax rates to the sample are projected to result in substantial decreases in smoking‐related costs and substantial increases in tax revenues.
Treatment of Burkitt lymphoma in equatorial Africa using a simple three‐drug combination followed by a salvage regimen for patients with persistent or recurrent disease
Authors: Ngoma Twalib , Adde Melissa , Durosinmi Muheez , Githang'a Jessie , Aken'Ova Yetunde , Kaijage Jane , Adeodou Oluwagbemiga , Rajab Jamilla , Brown Biobele J. , Leoncini Lorenzo , Naresh Kikkeri , Raphael Martine , Hurwitz Nina , Scanlan Patricia , Rohatiner Ama , Venzon David , Magrath Ian
Published: July 2012

Prior to the introduction of the International Network for Cancer Treatment and Research (INCTR) protocol INCTR 03‐06, survival of patients with Burkitt lymphoma at four tertiary care centres in equatorial Africa was probably no more than 10–20%. The results reported here for 356 patients have demonstrated marked improvement in survival through the use of a uniform treatment protocol consisting of cyclophosphamide, methotrexate, vincristine, and intrathecal therapy, and the introduction of non‐cross resistant second‐line (salvage) therapy, consisting of ifosfamide, mesna, etoposide and cytarabine, when patients failed to achieve a complete response to first‐line therapy or relapsed early. Overall survival rates of 67% and 62% were observed at 1 and 2 years (relapse is rare after 1 year of remission). Of interest was the small impact of cerebrospinal fluid (CSF) and bone marrow involvement on outcome. However, the presence or absence of abdominal involvement clearly defined two prognostic groups. An additional finding was the association between CSF pleocytosis and orbital tumours, suggesting that spread of tumour cells to the central nervous system may sometimes occur via direct involvement of cranial nerves in the orbit. Survival rates may be increased in patients with abdominal involvement by combining first‐ and second‐line therapy, but verification will require a further clinical study.
The rationale and pilot study of a new paediatric dental patient request form to improve communication and outcomes of dental appointments
Authors: Jones L. M. , Huggins T. J.
Published: July 2012

Background

Children's unhappy visits to the dentist can negatively impact lifelong oral health. A possible intervention is to enhance empathy in the child patient–dental practitioner relationship through communication. The present paper presents a new instrument, the Survey of Anxiety and Information for Dentists (SAID), which targets children's dental anxiety, coping preferences and dental neglect, and offers children a change to request information and engage in treatment planning.

Method

Five children's focus groups pilot tested the content, wording and response format of a prototype patient request form, the SAID. Participants were 34 10‐ to 13‐year‐old children who individually completed the form then discussed it item by item in their small groups.

Results

Children had no difficulty completing most items. They identified ambiguities, and items that were meaningless to them, and proposed a new item asking the dentist about their job. Children were polarized over the response format, but they were emphatic about passing the form directly to the dentist, and not to a receptionist or assistant, stressing the importance of having a conversation with their dentist.

Conclusions

Before the pilot, dentists had expressed concerns about the potential for words in the SAID‐provoking negative feelings. Children, however, wanted and needed facts, so requested that dentists use plain language, not euphemisms, to describe problems and treatment options. We report their selected practical suggestions. SAID‐informed negotiated care may promote more patient cooperation and satisfaction at appointments, and more attention to oral hygiene between appointments.
Molecular diagnosis on tissues and cells: how it affects training and will affect practice in the future
Authors: Boyd C. , Boyle D. P.
Published: July 2012

C. Boyd and D. P. Boyle  Molecular diagnosis on tissues and cells: how it affects training and will affect practice in the future

On 25th November 2011, a symposium organized by the Royal College of Pathologists, entitled ‘Molecular diagnosis on tissues and cells’, took place in London. As trainees in histopathology and cytopathology, we were stimulated to consider the role that molecular biology is likely to play in future practice and how this is addressed by our own training. The symposium provided a basis for this article. Routine samples requiring molecular analysis are equally relevant to histopathologists and cytopathologists, and molecular biology laboratories are now using cytological as well as histological material for diagnostic testing, allowing different specimen types to be used as and when they are most appropriate. The most widely used types of molecular analysis in routine cellular pathology are EGFR testing in lung cancer, molecular testing of thyroid nodules, fluorescence in situ hybridization testing of urine samples, clonality analysis in lymphoma testing, HER2 testing in breast and gastric cancer, KRAS testing in colorectal cancer, intraoperative assessment of breast cancer sentinel nodes, molecular testing of gastrointestinal stromal tumours and mismatch repair protein analysis. Of these, the majority in the UK are carried out on histopathology samples, although many are applicable to cytological samples if adequate material is obtained. We are particularly encouraged by the potential of molecular diagnostic cytology in traditionally difficult areas, such as intraoperative assessment. We believe that increasing reliance on molecular diagnostic techniques will also herald changes in training.
Nutrient reduction and climate change cause a potential shift from pelagic to benthic pathways in a eutrophic marine ecosystem
Authors: Lindegren Martin , Blenckner Thorsten , Stenseth Nils C.
Published: July 2012

The degree to which marine ecosystems may support the pelagic or benthic food chain has been shown to vary across natural and anthropogenic gradients for e.g., in temperature and nutrient availability. Moreover, such external forcing may not only affect the flux of organic matter but could trigger large and abrupt changes, i.e., trophic cascades and ecological regime shifts, which once having occurred may prove potentially irreversible. In this study, we investigate the state and regulatory pathways of the Kattegat; a eutrophied and heavily exploited marine ecosystem, specifically testing for the occurrence of regime shifts and the relative importance of multiple drivers, e.g., climate change, eutrophication and commercial fishing on ecosystem dynamics and trophic pathways. Using multivariate statistics and nonlinear regression on a comprehensive data set, covering abiotic factors and biotic variables across all trophic levels, we here propose a potential regime shift from pelagic to benthic regulatory pathways; a possible first sign of recovery from eutrophication likely triggered by drastic nutrient reductions (involving both nitrogen and phosphorus), in combination with climate‐driven changes in local environmental conditions (e.g., temperature and oxygen concentrations).
Persistence and production of perennial grasses under water deficits and extreme temperatures: importance of intraspecific vs. interspecific variability
Authors: Poirier Magalie , Durand Jean‐Louis , Volaire Florence
Published: July 2012

Extreme climatic events are expected to increase in frequency and magnitude as a consequence of global warming. Grasslands cover a large proportion of the European continent and contribute to both agricultural production and ecosystem services through inter and intraspecific genetic variability. This study analysed the effects of summer droughts and heat waves on the persistence and production of perennial forage grasses. Mediterranean and temperate populations of Dactylis glomerata L. and Festuca arundinacea (Schreb.) were compared at both Mediterranean and temperate sites in France. By manipulating canopy temperatures and water availability, grass swards in the field were subjected to cumulative summer and spring water deficits (CSSWD) ranging from 329 to 707 mm to test different projected climatic conditions and extreme summer events. Under controlled summer heat waves (6–21 days at a mean daily canopy temperature higher than 30–35 °C), there was no increase in membrane damage to surviving aerial tissues. Plant stress was thus mainly generated through greater soil water deficit. Under the greatest CSSWD, annual biomass production was reduced on average by 60% and 30% with temperate and Mediterranean populations, respectively. Thresholds for a significant increase in summer tiller mortality were seen at CSSWD higher than 450 mm for temperate populations and 550 mm for Mediterranean populations. The latter displayed lower predawn leaf water potentials in summer and recovered through intense tillering in the subsequent seasons. Under the most extreme CSSWD, fewer than 20% of tillers of temperate populations survived and their nitrogen uptake ability was drastically altered. The higher potential productivity of Mediterranean populations in winter was associated with greater frost sensitivity. The identification of thresholds for vulnerability and the determination of the role of genetic diversity will improve the management of plant resilience and the design of new plant material to cope with climate change.
Effects of written plus oral information vs. oral information alone on precolonoscopy anxiety
Authors: Luo Yuan‐Yuan
Published: July 2012

Aims and objectives:  To determine the effect of written plus oral information vs. oral information alone on precolonoscopy anxiety.

Background:  Information provision has been considered to reduce precolonoscopy anxiety. However, the best means to provide information before colonoscopy has not yet been determined as there is inconsistency in the outcomes of the clinical trials.

Design:  A two‐group, pretest, post‐test, prospective, quasi‐experimental design with non‐random assignment.

Methods:  Participants were assigned to group 1 or 2 in the study. In the enrolment all the participants completed the questionnaires to collect personal characteristics data and assessed subjects’ anxiety level by the Chinese version of the State Scale of State‐Trait Anxiety Inventory as baseline data. After that, subjects in group 1 received written plus oral information before colonoscopy, while those in group 2 received oral information before colonoscopy. On the day for colonoscopy all subjects completed the Chinese version of the State Scale of State‐Trait Anxiety Inventory again.

Results:  There was no difference in state anxiety and personal characteristic between the two groups at enrolment. After the intervention, although the state anxiety scores were dropped, there were no statistical significant differences between two groups or within groups 1 and 2.

Conclusions:  Information provision before colonoscopy did not reduce the anxiety level in patients directly before colonoscopy.

Relevance to clinical practice:  There was a trend that information had a positive effect on patients’ state anxiety. Future information provision studies may need to add more interactive methods appropriately and take patients’ gender, educational level and coping style into consideration.
The quality of clinical practice guidelines in China: a systematic assessment
Authors: Hu Jing , Chen Ru , Wu Shanshan , Tang Jinling , Leng Gillian , Kunnamo Ilkka , Yang Zhirong , Wang Weiwei , Hua Xinyang , Zhang Yuelun , Xie Yanming , Zhan Siyan
Published: July 2012

Background

Clinical guidelines are an important tool for improving service quality, the benefits of guidelines depend on their quality. In China, there has been a great increase in production of guidelines. However, little is known about their quality.

Method

We identified Chinese guidelines published between 2006 and 2010 by searching three Chinese full‐text databases, major Chinese guidelines websites and Google. Three appraisers independently evaluated each guideline by using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument. Subgroup analyses were performed according to source, title, version, aspect of care and developer of guidelines.

Results

A total of 327 guidelines were eligible and 57 were excluded for their lacking of any account of the guideline development methodology. Of the 270 guidelines, 77 (28.5%) can be recommended, 6 (2.2%) were evidence‐based guidelines. Sixteen (5.9%) guidelines described the methods used to search for evidence, 61 (22.6%) appraised the quality of evidence and 53 (19.6%) graded the strength of recommendations. Two guidelines declared the involvement of methodological experts and none reported considering patients’ values. 29 (10.7%) guidelines received drug company sponsorship but only two declared the views of the funding bodies did not influence the recommendations, 259 (95.9%) didn't declare the interest conflicts of guideline developers. Guidelines downloaded from Internet and with updated versions yielded higher quality than the rest.

Conclusions

Although numerous guidelines were produced in China, the quality was generally low. Focusing on improving the quality of Chinese guidelines, rather than continuing to produce them in great quantity, is urgently needed.
Stigma, public awareness about intellectual disability and attitudes to inclusion among different ethnic groups
Authors: Scior K. , Addai‐Davis J. , Kenyon M. , Sheridan J. C.
Published: July 2012

Background  Attitudes to the inclusion of people with intellectual disabilities (IDs) have been studied extensively, yet evidence on public awareness about ID and stigma is limited. The relationship between attitudes, knowledge and stigma associated with ID is poorly understood. The present study examined these factors and the relationships between them in the context of a multicultural society.

Method  UK residents of working age (n = 1002) were presented with a diagnostically unlabelled vignette of someone with a mild ID. They were asked to label the difficulties presented and to complete measures of social distance and attitudes to the inclusion of people with IDs.

Results  While attitudes to the inclusion of people with IDs were relatively positive overall, social contact was viewed with ambivalence. Inclusion attitudes and social distance were only moderately correlated. Across the whole sample 28% recognised typical symptoms of mild ID. Recognition of ID was associated with lower stigma and more positive attitudes than attribution of the difficulties presented to other causes. White Westerners showed increased knowledge, lower stigma and favoured inclusion more than participants from ethnic minorities. Among the latter group, Asians showed lower stigma and attitudes more in line with inclusion policies than participants of Black African/Caribbean backgrounds. Once a host of contextual factors were considered jointly, only contact was consistently associated with the variables measured.

Conclusions  Stigma associated with ID is of concern across all ethnic groups, although it appears to be increased among the public from ethnic minorities. Given that contact and awareness are associated with reduced stigma, they should be considered as prime foci for efforts to tackle ID stigma. The current findings serve as baseline for attempts to increase public awareness and tackle stigma.
The content validity of the Behaviour Support Plan Quality Evaluation tool (BSP‐QEII) and its potential application in accommodation and day‐support services for adults with intellectual disability
Authors: McVilly K. , Webber L. , Sharp G. , Paris M.
Published: July 2012

Background  The quality of support provided to people with disability who show challenging behaviour could be influenced by the quality of the behaviour support plans (BSPs) on which staff rely for direction. This study investigated the content validity of the Behaviour Support Plan Quality Evaluation tool (BSP‐QEII), originally developed to guide the development of BSPs for children in school settings, and evaluated its application for use in accommodation and day‐support services for adults with intellectual disability.

Method  A three‐round Delphi study involving a purposive sample of experienced behaviour support practitioners (n = 30) was conducted over an 8‐week period. The analyses included deductive content analysis and descriptive statistics.

Results  The 12 quality domains of the BSP‐QEII were affirmed as valid for application in adult accommodation and day‐support service settings. Two additional quality domains were suggested, relating to the provision of detailed background on the client and the need for plans to reflect contemporary service philosophy. Furthermore, the results suggest that some issues previously identified in the literature as being important for inclusion in BSPs might not currently be a priority for practitioners. These included: the importance of specifying replacement or alternative behaviours to be taught, descriptions of teaching strategies to be used, reinforcers, and the specification of objective goals against which to evaluate the success of the intervention programme.

Conclusions  The BSP‐QEII provides a potentially useful framework to guide and evaluate the development of BSPs in services for adults with intellectual disability. Further research is warranted to investigate why practitioners are potentially giving greater attention to some areas of intervention practice than others, even where research has demonstrated these others areas of practice could be important to achieving quality outcomes.