bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a culturally appropriate health‐related quality of life measure for human immunodeficiency virus‐infected children in Thailand
Authors: Punpanich Warunee , Hays Ron D , Detels Roger , Chokephaibulkit Kulkanya , Chantbuddhiwet Umaporn , Leowsrisook Pimsiri , Prasitsuebsai Wasana
Published: October 2010

Aim:  Develop a reliable and valid self‐report health‐related quality of life (HRQOL) instrument for human immunodeficiency virus (HIV)‐infected children in Thailand.

Methods:  The Thai Quality of Life for HIV‐infected Children instrument, the ThQLHC (an HRQOL measure that uses the Pediatric Quality of Life Inventory as a generic core and a 17‐item HIV‐targeted scale), was developed and administered cross‐sectionally to 292 HIV‐infected children in Thailand. The disease‐targeted scale included HIV‐related symptoms, ability to adhere with their treatment regimens and self‐image. The internal consistency reliability (Cronbach's α) and construct validity of the ThQLHC scales were then evaluated.

Results:  Internal consistency reliability coefficients ranged from 0.57 to 0.82, with four of five scales reaching the minimal acceptable level (>0.70). Significant associations were found between poor HRQOL and poor self‐rated disease severity, care giver's rated overall quality of life, cluster of differentiation (CD) 4 percent and plasma HIV ribonucleic acid level.

Conclusion:  Reliable and valid disease‐targeted HRQOL measures for HIV‐infected children are essential in the assessment of therapeutic effectiveness. The findings of this cross‐sectional survey provide support for the reliability and validity of the ThQLHC as an HRQOL outcome measure for HIV‐infected Thai children.
Has anti‐D prophylaxis increased the rate of positive direct antiglobulin test results and can the direct antiglobulin test predict need for phototherapy in Rh/ABO incompatibility?
Authors: Dillon Alexander , Chaudhari Tejasvi , Crispin Phillip , Shadbolt Bruce , Kent Alison
Published: October 2010

Aim:  To determine the impact of Rhesus (Rh) D prophylaxis on positive direct antiglobulin test (DAT) results and ability of a DAT grade to predict an infant's need for phototherapy.

Methods:  Laboratory and infant medical records were reviewed for DAT status, DAT grade, interventions for hyperbilirubinemia including phototherapy, blood transfusion, exchange transfusion and intravenous immunoglobulin. Two epochs of DAT results were reviewed, the first in the era prior to Rh D prophylaxis, the second after introduction of standardised Rh D prophylaxis for Rh negative women.

Results:  A total of 165 DAT‐positive infants' medical records were reviewed. The number of positive DAT results increased from 1.5% to 2.3% (P < 0.0001) following introduction of anti‐Rh D prophylaxis, the increase related to an increase in anti‐D DATs (7.4% to 32% –P < 0.0001). An infant with a DAT grade of 5–8 was 2.6 times more likely to need phototherapy than an infant with a DAT grade of 2–4 (odds ratio (OR), 2.571; 95% confidence interval (CI), 1.225–5.393; P = 0.08) and an infant with a DAT grade of 10–12 was 4.7 times more likely to need phototherapy than an infant with a DAT grade of 2–4 (OR, 4.724; 95% CI, 1.602–13.926, P = 0.013).

Conclusions:  Rh D prophylaxis has increased positive DAT results, which may increase the number of unnecessary bilirubin measurements. A low or high DAT grade is strongly predictive of whether an infant does or does not require phototherapy. However, an intermediate DAT requires concomitant bilirubin measurements to determine phototherapy requirements.
Culturable Rhodobacter and Shewanella species are abundant in estuarine turbidity maxima of the Columbia River
Authors: Bräuer S. L. , Adams C. , Kranzler K. , Murphy D. , Xu M. , Zuber P. , Simon H. M. , Baptista A. M. , Tebo B. M.
Published: October 2010

Measurements of dissolved, ascorbate‐reducible and total Mn by ICP‐OES revealed significantly higher concentrations during estuarine turbidity maxima (ETM) events, compared with non‐events in the Columbia River. Most probable number (MPN) counts of Mn‐oxidizing or Mn‐reducing heterotrophs were not statistically different from that of other heterotrophs (103–104 cells ml−1) when grown in defined media, but counts of Mn oxidizers were significantly lower in nutrient‐rich medium (13 cells ml−1). MPN counts of Mn oxidizers were also significantly lower on Mn(III)‐pyrophosphate and glycerol (21 cells ml−1). Large numbers of Rhodobacter spp. were cultured from dilutions of 10−2 to 10−5, and many of these were capable of Mn(III) oxidation. Up to c. 30% of the colonies tested LBB positive, and all 77 of the successfully sequenced LBB positive colonies (of varying morphology) yielded sequences related to Rhodobacter spp. qPCR indicated that a cluster of Rhodobacter isolates and closely related strains (95–99% identity) represented approximately 1–3% of the total Bacteria, consistent with clone library results. Copy numbers of SSU rRNA genes for either Rhodobacter spp. or Bacteria were four to eightfold greater during ETM events compared with non‐events. Strains of a Shewanella sp. were retrieved from the highest dilutions (10−5) of Mn reducers, and were also capable of Mn oxidation. The SSU rRNA gene sequences from these strains shared a high identity score (98%) with sequences obtained in clone libraries. Our results support previous findings that ETMs are zones with high microbial activity. Results indicated that Shewanella and Rhodobacter species were present in environmentally relevant concentrations, and further demonstrated that a large proportion of culturable bacteria, including Shewanella and Rhodobacter spp., were capable of Mn cycling in vitro.
Novel use of an air‐filled breast prosthesis to allow radiotherapy to recurrent colonic cancer
Authors: O’Duffy F. , Toomey D. P. , Fleming F. , McNamara D. A.
Published: October 2010

Aim  The authors present the novel and successful use of an air‐filled breast prosthesis for extra pelvic exclusion of small bowel to facilitate adjuvant radiotherapy following resection of recurrent adenocarcinoma of the ascending bowel. The therapeutic use of radiotherapy in colon cancer can cause acute or chronic radiation enteropathy. Mobile small bowel can be sequestered in ‘dead space’ or by adhesions exposing it to adjuvant radiotherapy. A variety of pelvic partitioning methods have been described to exclude bowel from radiation fields using both native and prosthetic materials.

Method  In this case a 68 year old presented with ascending colon adenocarcinoma invading the peritoneum and underwent en bloc peritoneal resection. Thirty‐seven months later surveillance CT identified a local recurrence. Subsequent resection resulted in a large iliacus muscle defect which would sequester small bowel loops thus exposing the patient to radiation enteropathy. The lateral position of the defect precluded the use of traditional pelvic partitioning methods which would be unlikely to remain in place long enough to allow radiotherapy. A lightweight air‐filled breast prosthesis (Allergan 133 FV 750 cms) secured in place with an omentoplasty was used to fill the defect.

Results  Following well tolerated radiotherapy the prosthesis was deflated under ultrasound guidance and removed via a 7‐cm transverse incision above the right iliac crest. The patient is disease free 18 months later with no evidence of treatment related morbidity.

Conclusion  The use of a malleable air‐filled prosthesis for pelvic partitioning allows specific tailoring of the prosthesis size and shape for individual patient defects. It is also lightweight enough to be secured in place using an omentoplasty to prevent movement related prosthesis migration. In the absence of adequate omentum a mesh sling may be considered to allow fixation. In this case the anatomy of the prosthesis position allowed for its removal without the need for repeat laparotomy. Pre‐operative deflation of the air‐filled prosthesis under ultrasound guidance also reduces the size of the incision required for removal. This technique may be valuable to prevent collateral small bowel irradiation following resection of renal or retroperitoneal malignancy.
Hospital discharge criteria following colorectal surgery:a systematic review
Authors: Fiore J. F. , Browning L. , Bialocerkowski A. , Gruen R. L. , Faragher I. G. , Denehy L.
Published: October 2010

Aim  The aim of this study was to identify and synthesize the hospital discharge criteria that have been used in the colorectal surgery literature.

Methods  A systematic literature search was conducted using eight bibliographic databases. Searches were limited to English language journal articles published between January 1996 and October 2009. Primary research applying hospital discharge criteria following colorectal surgery was included. Study selection was made independently by two reviewers. Discharge criteria were extracted from each included study.

Results  The 156 studies identified by the search strategy described 70 different sets of criteria to indicate readiness for discharge. The majority of studies applied a combination of three or four criteria; those most frequently cited were tolerance of oral intake (80%), return of bowel function (70%), adequate pain control (44%) and adequate mobility (35%). End‐points employed to determine the achievement of criteria were generally poorly defined.

Conclusion  A variety of hospital discharge criteria were applied in the colorectal surgery literature. Development of standardized criteria will allow more accurate comparison of results between studies assessing hospital length of stay or other discharge‐related outcome measures.
A placebo‐controlled trial of exenatide twice‐daily added to thiazolidinediones alone or in combination with metformin
Authors: Liutkus J. , Rosas Guzman J. , Norwood P. , Pop L. , Northrup J. , Cao D. , Trautmann M.
Published: October 2010

Aim: To test the hypothesis that glycaemic control with exenatide added to thiazolidinediones (TZDs) with or without metformin was superior to placebo.

Methods: A 26‐week, multi‐country (Canada, Mexico, Romania, South Africa and the USA), randomized, double‐blind, placebo‐controlled study compared exenatide twice‐daily vs. placebo in 165 subjects suboptimally controlled with TZDs with or without metformin [HbA1c 8.2% (s.d. 0.9), fasting serum glucose 9.1 (2.6) mmol/l, body weight 93.9 (17.8) kg, diabetes duration 6.4 (4.3) years]. After a 2‐week, single‐blind, lead‐in period, subjects were randomly assigned (2 : 1) to add exenatide or placebo to current regimens. The primary endpoint was HbA1c change at endpoint (Week 26 or last‐observation‐carried‐forward).

Results: Only 8 subjects were treated with concomitant TZD alone. Exenatide reduced HbA1c significantly more than placebo [−0.84% (s.e. 0.20) vs. −0.10% (0.23), treatment difference −0.74% (0.16), p < 0.001)]. Mean reductions in body weight were similar in both treatments at endpoint [exenatide, −1.4 (s.e. 0.6) kg vs. placebo, −0.8 (0.7) kg, p = 0.176)]. Nearly 71% of subjects had both a reduction in HbA1c and body weight with exenatide compared with 54% with placebo. The most common adverse events (exenatide vs. placebo) were nausea (12% vs. 2%, p = 0.037), vomiting (8% vs. 0%, p = 0.031) and headache (4% vs. 4%). Confirmed (blood glucose <3.0 mmol/l) minor hypoglycaemia was experienced by 4 and 2% of subjects treated with exenatide and placebo, respectively. Incidence of hypoglycaemia was not significantly different between groups.

Conclusions: Exenatide added to TZDs alone or in combination with metformin significantly improved glycaemic control as determined by significant improvement in HbA1c without associated hypoglycaemia.
Internet‐based interventions for problem drinkers: From efficacy trials to implementation
Authors: CUNNINGHAM JOHN A. , KHADJESARI ZARNIE , BEWICK BRIDGETTE M. , RIPER HELEEN
Published: October 2010

Aims. Internet‐based interventions (IBIs) for problem drinkers have been in existence for over a decade. In that time, IBIs have increased in sophistication and there is the beginning of a solid research base suggesting their efficacy. A growing number of problem drinkers are using IBIs and attempts have been made to explore how IBIs can be integrated within primary care and other health‐care settings. This symposium provided an overview of IBIs for problem drinkers and highlighted some of the important issues in their development and implementation.

Rationale. IBIs appear to be at a ‘cusp’ as technology and intervention practices are merged together in an attempt to provide better health care for problem drinkers. The timing of the 2009 International Network on Brief Interventions for Alcohol Problems Conference was ideal for a presentation and discussion of the role that IBIs play now that IBIs have started to shift into the mainstream of services for problem drinkers.

Summary. The presentations in this symposium covered the ‘bench to bedside’ aspects of the development and evaluation of IBIs. They included a systematic review of the research to‐date in this field, a report on the results from a just completed randomised controlled trial, a report on an effectiveness trial of implementing IBIs in multiple university settings and a consideration of the cost‐effectiveness of IBIs.[Cunningham JA, Khadjesari Z, Bewick BM, Riper H. Internet‐based interventions for problem drinkers: From efficacy trials to implementation. Drug Alcohol Rev 2010;29;617–622]
Alcohol screening and brief intervention in primary care: Absence of evidence for efficacy in people with dependence or very heavy drinking
Authors: SAITZ RICHARD
Published: October 2010

Issues. Although screening and brief intervention (BI) in the primary‐care setting reduces unhealthy alcohol use, its efficacy among patients with dependence has not been established. This systematic review sought to determine whether evidence exists for BI efficacy among patients with alcohol dependence identified by screening in primary‐care settings.

Approach. We included randomised controlled trials (RCTs) extracted from eight systematic reviews and electronic database searches published through September 2009. These RCTs compared outcomes among adults with unhealthy alcohol use identified by screening who received BI in a primary‐care setting with those who received no intervention.

Key Findings. Sixteen RCTs, including 6839 patients, met the inclusion criteria. Of these, 14 excluded some or all persons with very heavy alcohol use or dependence; one in which 35% of 175 patients had dependence found no difference in an alcohol severity score between groups; and one in which 58% of 24 female patients had dependence showed no efficacy.

Conclusion and Implications. Alcohol screening and BI has efficacy in primary care for patients with unhealthy alcohol use, but there is no evidence for efficacy among those with very heavy use or dependence. As alcohol screening identifies both dependent and non‐dependent unhealthy use, the absence of evidence for the efficacy of BI among primary‐care patients with screening‐identified alcohol dependence raises questions regarding the efficiency of screening and BI, particularly in settings where dependence is common. The finding also highlights the need to develop new approaches to help such patients, particularly if screening and BI are to be disseminated widely.[Saitz R. Alcohol screening and brief intervention in primary care: Absence of evidence for efficacy in people with dependence or very heavy drinking. Drug Alcohol Rev 2010;29;631–640]
NICE work if you can get it: Development of national guidance incorporating screening and brief intervention to prevent hazardous and harmful drinking in England
Authors: KANER EILEEN
Published: October 2010

This paper describes the development of the first set of national guidance focused on the prevention of alcohol problems in England. These guidelines were produced by the National Institute for Health and Clinical Excellence (NICE) working with a multidisciplinary program development group of scientists, practitioners and lay members. In this work, screening and brief alcohol interventions represent a key element of a comprehensive public health strategy to prevent alcohol‐related risk and harm across the population. The first controlled trials of brief alcohol intervention were published in the mid to late 1980's and there are now around 60 published trials in this field. After 25 years of accumulated evidence in this field, brief alcohol interventions have yet to make a significant impact on routine clinical practice. While it is imperative to have good science to make the case for brief intervention delivery, this work is in vain if practitioners are unwilling or unable to use these interventions with their patients. Evidence from the alcohol field and other clinical areas indicates that national prioritisation of brief alcohol intervention activity, by a body, such as NICE, is likely to be a key driver of implementation by practitioners. This paper summarises a suite of complementary system‐level and practice recommendations, which were published by NICE in June 2010, and considers their likely impact on screening and brief alcohol in England.[Kaner E. NICE work if you can get it: Development of national guidance incorporating screening and brief intervention to prevent hazardous and harmful drinking in England. Drug Alcohol Rev 2010;29;589–595]
Grasping the thistle: The role of alcohol brief interventions in Scottish alcohol policy
Authors: GRAHAM LESLEY J. C. , MACKINNON DONNA
Published: October 2010

Issue.Scotland has experienced a substantial rise in alcohol‐related harm, which is now one of the biggest public health challenges it faces.

Approach.Alcohol problems in Scotland are described along with national alcohol policy response in addressing them. The role of a program of Alcohol Brief Interventions is discussed therein.

Key Findings.In Scotland, considerable proportions of the population are drinking hazardously or harmfully, common across different age and socioeconomic groups. Rising consumption has been set in wider environmental changes with alcohol becoming more available and affordable. Scotland has had one of the fastest growing chronic liver disease mortality rates in the world at a time when rates in most of Western Europe are falling. Scotland's alcohol policy has an explicit aim to reduce population consumption and includes legislative measures to tackle price and availability. A national program to deliver Alcohol Brief Interventions for hazardous drinkers is a key plank of this wider strategy. A portfolio of studies will monitor and evaluate national policy and, through contribution analysis, describe the role Alcohol Brief Interventions play in reducing alcohol misuse.

Implications.Effective alcohol policy recognises that determinants of health not only lie at individual level, but include wider social, environmental and economic factors. Scotland's policy is addressing these determinants with both population‐based and population‐targeted interventions.

Conclusion.Scotland has a serious problem with alcohol. A comprehensive, evidence‐based, resourced alcohol policy is being implemented, which will need continual review to ensure it remains anchored in evidence while maintaining its ambition.[Graham LJC, MacKinnon D. Grasping the thistle: The role of alcohol brief interventions in Scottish alcohol policy.Drug Alcohol Rev2010;29;603–607]
Development of relational reasoning during adolescence
Authors: Dumontheil Iroise , Houlton Rachael , Christoff Kalina , Blakemore Sarah‐Jayne
Published: October 2010

Non‐linear changes in behaviour and in brain activity during adolescent development have been reported in a variety of cognitive tasks. These developmental changes are often interpreted as being a consequence of changes in brain structure, including non‐linear changes in grey matter volumes, which occur during adolescence. However, very few studies have attempted to combine behavioural, functional and structural data. This multi‐method approach is the one we took in the current study, which was designed to investigate developmental changes in behaviour and brain activity during relational reasoning, the simultaneous integration of multiple relations. We used a relational reasoning task known to recruit rostrolateral prefrontal cortex (RLPFC), a region that undergoes substantial structural changes during adolescence. The task was administered to female participants in a behavioural (N = 178, 7–27 years) and an fMRI study (N = 37, 11–30 years). Non‐linear changes in accuracy were observed, with poorer performance during mid‐adolescence. fMRI and VBM results revealed a complex picture of linear and possibly non‐linear changes with age. Performance and structural changes partly accounted for changes with age in RLPFC and medial superior frontal gyrus activity but not for a decrease in activation in the anterior insula/frontal operculum between mid‐adolescence and adulthood. These functional changes might instead reflect the maturation of neurocognitive strategies.
Assessing Similarity of DNA profiles
Authors: Hepworth Graham , Gordon Ian
Published: October 2010

The genetic similarity of strains of a pathogen can be assessed by using a matrix of dissimilarities that is derived from bands in their DNA profile which are present or absent. The dependence between elements of the dissimilarity matrix, if not accounted for, results in underestimation of the variance in comparisons between groups of strains which are differentiated according to the possession of an attribute. We examine a previously proposed statistic for determining whether a group of strains is more similar than expected. We show the limitations of this statistic and propose a new statistic which better addresses the hypotheses that are usually considered in this field of study. The statistic proposed is based on similarity between strains within the group of interest and with those outside. This statistic also needs to account for the dependence in the raw data, and we use the correlation between elements of the dissimilarity matrix to investigate how this dependence affects the underestimation of the variance. Using examples involving the pathogenic yeast Candida, we show how permutation tests can be applied to the differentiation of groups of strains.
Geochemical and isotopic characterization of volcanic and geothermal fluids discharged from the Ecuadorian volcanic arc
Authors: INGUAGGIATO S. , HIDALGO S. , BEATE B. , BOURQUIN J.
Published: October 2010

The Ecuadorian Quaternary volcanic arc is characterized by about 60 volcanoes many of which are active or potentially active. This volcanic activity is the result of the subduction processes of the Nazca Plate beneath the north‐western part of South America. The geochemical signature of the discharged fluids from these volcanic systems gives an important contribution to the comprehension of the subduction processes in the South‐American region. In this work, we present the first systematic geochemical characterization of discharged fluids from the entire Ecuadorian volcanic arc on the basis of the chemical and isotopic composition of 56 samples of thermal and cold waters, as well as 32 dissolved and 27 bubbling gases collected from north to south across the arc. The isotopic composition of waters reveals a mainly meteoric origin, while the chemistry of the dissolved gases is characterized by He and CO2 contents, 2–3 orders of magnitude higher than the air saturated water values, which implies very active gas–water interaction processes with deep fluids. Moreover, both dissolved and bubbling gases’ isotopic signature shows a wide compositional range, with helium ranging between 0.1 and 7.12 R/Ra and carbon ranging from −1.75 to −10.50‰δ13C(TDIC). Such isotopic features may be related to the presence of at least two distinct end‐member sources: the mantle and the crust. Finally, this geochemical study clearly reveals the two distinct geographic parts of the arc, showing different isotopic characteristics of fluids for the Quaternary active volcanism, (north of 2°S), and for the inactive arc, (south of 2°S).
Gas geochemistry related to wellhead production data to investigate physical reservoir phenomena in geothermal reservoirs: application at Cerro Prieto IV (Mexico)
Authors: BARRAGÁN R. M. , ARELLANO V. M. , RODRÍGUEZ M. H. , PÉREZ A. , SEGOVIA N.
Published: October 2010

The chemical composition of the steam discharged by wells at the Cerro Prieto IV (CP IV) sector of the Cerro Prieto (Mexico) geothermal field was used to estimate important reservoir parameters such as steam fractions at the entrance of the wells (also called ‘excess steam’) and volumetric liquid saturations in the reservoir. The results were analyzed together with chemical and wellhead production data over a time interval to investigate physical phenomena in the reservoir fluid induced by exploitation practices. For starting conditions, the reservoir temperatures at CP IV sector were estimated to be between 270 and 320°C; relatively high reservoir liquid saturations (>0.9) were estimated at the northwest and at the center of the sector, while at the southeast moderate liquid saturations (<0.2) were found. The main reservoir physical processes included (i) moderate boiling with enthalpy increases to values consistently lower than that for the steam (2676 kJ kg−1) and with preferential flow of steam to the wells in the periphery of CP IV, (except toward the north), (ii) the entry of shallower, cooler waters into the reservoir at the center of the CP IV sector; and (iii) widespread boiling with high‐temperature steam condensation in the south and east of the sector. In some CP IV wells, separated entries for pre‐existent reservoir steam and reservoir liquid were identified. According to the analysis of 2005 data, relatively high temperatures (>300°C), high reservoir steam fractions (>0.4), and relatively low volumetric liquid saturations (<0.2) were estimated for fluids entering wells located along the southeast of CP IV. However, at the center of the sector the inflow of cooler waters moving down through the Fault H system was inferred to occur and was related to exploitation.
Individual variation in migratory movements and winter behaviour of Iberian Lesser Kestrels Falco naumanni revealed by geolocators
Authors: CATRY INÊS , DIAS MARIA P. , CATRY TERESA , AFANASYEV VSEVOLOD , FOX JAMES , FRANCO ALDINA M.A. , SUTHERLAND WILLIAM J.
Published: October 2010

The population decline of the Lesser Kestrel Falco naumanni has been the subject of studies across its Western Palaearctic breeding range, but little is known about its use of pre‐migratory areas or African wintering quarters. We used geolocators to describe the temporal and spatial patterns of Portuguese Lesser Kestrel migration and wintering behaviour. Data on the complete migration were obtained from four individuals and another three provided further information. Prior to southward migration, Lesser Kestrels showed two different behaviours: northward‐orientated movements to Spain and movements in the proximity of the breeding area. Autumn migration took place mostly in late September; spring departures occurred mainly in the first half of February. Wintering grounds included Senegal, Mauritania and Mali, with individuals overlapping considerably in Senegal. Movements registered within the wintering grounds suggest itinerant behaviour in relation to local flushes of prey. During spring migration, birds crossed the Sahara Desert through Mauritania, Western Sahara and Morocco before passing over the Mediterranean to reach Portugal. Autumn migration lasted 4.8 ± 1.1 days, and spring migration lasted 4.1 ± 0.3 days. The mean daily flight range varied between approximately 300 and 850 km for an entire journey of around 2500 km. Effective protection of roosting sites in both pre‐migratory and wintering areas and maintaining grasshopper populations in Sahelian wintering quarters appear crucial in preserving this threatened migratory raptor across its African–Eurasian flyway. There was no evidence of any deleterious effects of fitting birds with loggers.
Co‐operative signalling through DP1 and DP2 prostanoid receptors is required to enhance leukotriene C4 synthesis induced by prostaglandin D2 in eosinophils
Authors: Mesquita‐Santos FP , Bakker‐Abreu I , Luna‐Gomes T , Bozza PT , Diaz BL , Bandeira‐Melo C
Published: October 2010

BACKGROUND AND PURPOSE Prostaglandin (PG) D2 has emerged as a key mediator of allergic inflammatory pathologies and, particularly, PGD2 induces leukotriene (LT) C4 secretion from eosinophils. Here, we have characterized how PGD2 signals to induce LTC4 synthesis in eosinophils.

EXPERIMENTAL APPROACH Antagonists and agonists of DP1 and DP2 prostanoid receptors were used in a model of PGD2‐induced eosinophilic inflammation in vivo and with PGD2‐stimulated human eosinophils in vitro, to identify PGD2 receptor(s) mediating LTC4 secretion. The signalling pathways involved were also investigated.

KEY RESULTS In vivo and in vitro assays with receptor antagonists showed that PGD2‐triggered cysteinyl‐LT (cysLT) secretion depends on the activation of both DP1 and DP2 receptors. DP1 and DP2 receptor agonists elicited cysLTs production only after simultaneous activation of both receptors. In eosinophils, LTC4 synthesis, but not LTC4 transport/export, was activated by PGD2 receptor stimulation, and lipid bodies (lipid droplets) were the intracellular compartments of DP1/DP2 receptor‐driven LTC4 synthesis. Although not sufficient to trigger LTC4 synthesis by itself, DP1 receptor activation, signalling through protein kinase A, did activate the biogenesis of eosinophil lipid bodies, a process crucial for PGD2‐induced LTC4 synthesis. Similarly, concurrent DP2 receptor activation used Pertussis toxin‐sensitive and calcium‐dependent signalling pathways to achieve effective PGD2‐induced LTC4 synthesis.

CONCLUSIONS AND IMPLICATIONS Based on pivotal roles of cysLTs in allergic inflammatory pathogenesis and the collaborative interaction between PGD2 receptors described here, our data suggest that both DP1 and DP2 receptor antagonists might be attractive candidates for anti‐allergic therapies.

LINKED ARTICLE This article is commented on by Mackay and Stewart, pp. 1671–1673 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01236.x
Roles of affinity and lipophilicity in the slow kinetics of prostanoid receptor antagonists on isolated smooth muscle preparations
Authors: Jones RL , Woodward DF , Wang JW , Clark RL
Published: October 2010

BACKGROUND AND PURPOSEThe highly lipophilic acyl‐sulphonamides L‐798106 and L‐826266 showed surprisingly slow antagonism of the prostanoid EP3receptor system in guinea‐pig aorta. Roles of affinity and lipophilicity in the onset kinetics of these and other prostanoid ligands were investigated.

EXPERIMENTAL APPROACHAntagonist selectivity was assessed using a panel of human recombinant prostanoid receptor‐fluorimetric imaging plate reader assays. Potencies/affinities and onset half‐times of agonists and antagonists were obtained on guinea‐pig‐isolated aorta and vas deferens.n‐Octanol‐water partition coefficients were predicted.

KEY RESULTSL‐798106, L‐826266 and the less lipophilic congener (DG)‐3ap appear to behave as selective, competitive‐reversible EP3antagonists. For ligands of low to moderate lipophilicity, potency increments for EP3and TP (thromboxane‐like) agonism on guinea‐pig aorta (above pEC50of 8.0) were associated with progressively longer onset half‐times; similar trends were found for TP and histamine H1antagonism above a pA2limit of 8.0. In contrast, L‐798106 (EP3), L‐826266 (EP3, TP) and the lipophilic H1antagonists astemizole and terfenadine exhibited very slow onset rates despite their moderate affinities; (DG)‐3ap (EP3) had a faster onset. Agonism and antagonism on the vas deferens EP3system were overall much faster, although trends were similar.

CONCLUSIONS AND IMPLICATIONSHigh affinity and high liphophilicity may contribute to the slow onsets of prostanoid ligands in some isolated smooth muscle preparations. Both relationships are explicable by tissue disposition under the limited diffusion model. EP3antagonists used as research tools should have moderate lipophilicity. The influence of lipophilicity on the potential clinical use of EP3antagonists is discussed.
Interaction of diltiazem with an intracellularly accessible binding site on CaV1.2
Authors: Shabbir W , Beyl S , Timin EN , Schellmann D , Erker T , Hohaus A , Hockerman GH , Hering S
Published: October 2010

BACKGROUND AND PURPOSEDiltiazem inhibits CaV1.2 channels and is widely used in clinical practice to treat cardiovascular diseases. Binding determinants for diltiazem are located on segments IIIS6, IVS6 and the selectivity filter of the pore forming α1subunit of CaV1.2. The aim of the present study was to clarify the location of the diltiazem binding site making use of its membrane‐impermeable quaternary derivative d‐cis‐diltiazem (qDil) and mutant α1subunits.

EXPERIMENTAL APPROACHCaV1.2 composed of α1, α2‐δ and β2a subunits were expressed in tsA‐201 cells and barium currents through CaV1.2 channels were recorded using the patch clamp method in the whole cell configuration. qDil was synthesized and applied to the intracellular side (via the patch pipette) or to the extracellular side of the membrane (by bath perfusion).

KEY RESULTSQuaternary derivative d‐cis‐diltiazem inhibited CaV1.2 when applied to the intracellular side of the membrane in a use‐dependent manner (59 ± 4% at 300 µM) and induced only a low level of tonic (non‐use‐dependent) block (16 ± 2% at 300 µM) when applied to the extracellular side of the membrane. Mutations in IIIS6 and IVS6 that have previously been shown to reduce the sensitivity of CaV1.2 to tertiary diltiazem also had reduced sensitivity to intracellularly applied qDil.

CONCLUSION AND IMPLICATIONSThe data show that use‐dependent block of in CaV1.2 by diltiazem occurs by interaction with a binding site accessible via a hydrophilic route from the intracellular side of the membrane.
Fatherly violence, motherly absence, servants' resistance in Shakespeare and his time
Authors: SHIN HIEWON
Published: October 2010

This essay explores the significant roles played by non‐relatives who function as mother‐surrogates to endangered children. The essay introduces the non‐relatives, including servants, who intervene on behalf of passive mothers to confront violent masters/ fathers. The essay challenges the Renaissance dichotomy between loving biological parent and dangerous non‐biological parent by taking up various literary examples of violent fathers, passive mothers, and active non‐relatives who serve as the only protector/ guardian of the child in danger. The essay also points out the Renaissance addition of the active servant as a way to show a changing social environment. The resistance on the part of non‐relatives is a Renaissance addition to the medieval representations of famous stories of patient Griselda: Petrarch, Boccaccio, and Chaucer, focusing on the silent mother who easily succumbs to her husband's child murder, do not provide any equivalent to the Renaissance creation of non‐relatives as an active guardian of the child in danger. By focusing on the need for non‐biological parents who provide safety to children from their biological parents' violence, this essay explains why surrogate parents emerge as a necessity in Renaissance England and why tyrannous patriarchal violence is legitimately resisted.
Landscape Pattern Dynamics and Mechanisms during Vegetation Restoration: A Multiscale, Hierarchical Patch Dynamics Approach
Authors: Peng Shaolin , Zhou Ting , Liang Liyin , Ren Wentao
Published: October 2010

The spatial pattern of vegetation changes during ecological restoration, and these changes are affected by the process of restoration. The objective of this study was to integrate the pattern and mechanism of forest restoration in the Dinghushan Nature Reserve (DNR), Guangdong, China, based on data from remote sensing and long‐term field observations. We studied the pattern dynamics of three main forest types and their underlying mechanisms during restoration following a multiscale, hierarchical patch dynamics framework that integrates population, community, and landscape processes. Remote sensing data were used to determine the changes in landscape pattern during different periods of forest restoration from 1978 to 2006. At the landscape scale, the number, area, and perimeter of the needle/broad‐leaved mixed forest (MF) and the evergreen broad‐leaved forest (BF) increased, whereas those of the tropical needle‐leaved forest (NF) decreased during succession. Our analysis based on long‐term field observations indicated that the change rate of NF was lower than that of MF during 1981–1996, but became much higher during 1996–2007. The rate of change in landscape pattern and the progression of succession stages were consistent with each other. Our results also showed that species regeneration and community succession are the biological basis of forest landscape dynamics during vegetation restoration. Landscape pattern analysis allowed us to show “what” happened during vegetation restoration and “where,” and population and community analysis indicated “why” and “how” it happened.
Restoration of Shorebird‐Roosting Mudflats by Partial Removal of Estuarine Mangroves in Northern Taiwan
Authors: Huang Shou‐Chung , Shih Shang‐Shu , Ho Yi‐Shen , Chen Chang‐Po , Hsieh Hwey‐Lian
Published: October 2010

Expansion of the monospecific mangrove, Kandelia obovata, has converted intertidal mudflats and other habitats into mangrove forests, thus reducing estuarine biodiversity in the Danshuei River estuary, northern Taiwan. Dense mangrove vegetation was removed to create a small patchwork of mudflats and a tidal creek in February 2007. Subsequent changes in sediment properties and biodiversity of the macrobenthos and avian communities were examined. The results showed that the creation of different habitats led to changes in sediment properties and biodiversity. The water content and sorting degree of the sediments differed significantly among the restored mudflat, the tidal creek, and the mangrove control site. Silt/clay, organic carbon content, and chlorophyll a concentrations varied seasonally, but not among sites. The abundance of polychaetes in the creek was greater than that in the mudflat or the mangrove (12.5 vs. 5.3 and 2.2 individuals/m2, respectively), suggesting preferential colonization of infaunal polychaetes in habitats with prolonged submersion. Crabs showed seasonal changes in density, with higher densities in summer than in autumn and winter. The species richness of wintering shorebirds on the created mudflat increased dramatically from 2002 to 2007. The transformation of a vegetated area into an open mudflat appeared to benefit shorebirds by providing roosting habitat. Our study demonstrated that controlling the spread of estuarine mangrove forests could increase biodiversity, and could particularly benefit the migratory shorebird community.
The frequency and specificity of human neutrophil antigen antibodies in a blood donor population
Authors: Gottschall Jerome L. , Triulzi Darrell J. , Curtis Brian , Kakaiya Ram M. , Busch Michael P. , Norris Philip J. , Glynn Simone A. , Carrick Danielle , Wright David J. , Kleinman Steve
Published: October 2010

BACKGROUND: Transfusion‐related acute lung injury (TRALI) has been associated with both human leukocyte antigen (HLA) and human neutrophil antigen (HNA) antibodies. HNA antibody frequency, specificity, and demographic associations have not been well defined in the blood donor population.

STUDY DESIGN AND METHODS: A subset of 1171 donors (388 nontransfused males, 390 HLA antibody–negative females with three or more pregnancies, and 393 HLA antibody–positive females with three or more pregnancies) from a larger Leukocyte Antibody Prevalence Study was tested for immunoglobulin (Ig)G and IgM HNA antibody using a granulocyte immunofluorescence flow cytometry assay. Additional testing on selected samples included monoclonal antibody immobilization of granulocyte antigen–flow cytometry and granulocyte genotyping.

RESULTS: Eight samples were HNA antibody positive (prevalence, 0.7%; 95% confidence interval [CI], 0.3%‐1.3%]). Three HNA antibodies (one IgG and two IgM) were found in nontransfused males (prevalence, 0.8%; 95% CI, 0.2%‐2.2%); all were panreactive or nonspecific. One HLA antibody–negative previously pregnant female had an IgG HNA antibody with HNA‐1a specificity (prevalence, 0.3%; 95% CI, 0.01%‐1.4%). Four HLA antibody–positive previously pregnant females demonstrated HNA antibodies, three IgG and one IgM (prevalence, 1%; 95% CI, 0.3%‐2.6%). Two of these were HNA‐1a specific, one HNA‐4a specific, and one nonspecific.

CONCLUSIONS: HNA antibodies occur with low frequency in the donor population and are present in both male and female donors. Despite the implementation of TRALI reduction strategies, HNA antibodies are still present in donor blood products. Although our data do not create a case for urgent implementation of donor HNA antibody testing, future new developments for high‐throughput HNA antibody screening, including for HNA‐3a, may warrant reconsideration.
Impact of pathogen reduction technology and storage in platelet additive solutions on platelet function
Authors: Galan Ana M. , Lozano Miguel , Molina Patricia , Navalon Fulgencio , Marschner Sussane , Goodrich Raymond , Escolar Ginés
Published: October 2010

BACKGROUND: There are limited studies on the effect of pathogen reduction technology (PRT) on platelet (PLT) products stored in PLT additive solutions (PASs). Our study has evaluated the effect of Mirasol PRT (CaridianBCT) followed by storage in PASs (PAS‐III or PAS‐IIIM) on analytical and functional characteristics of PLT concentrates (PCs).

STUDY DESIGN AND METHODS: PCs obtained by apheresis were divided into: 1) untreated and stored in plasma (CON‐PPP); 2) untreated and stored in PAS (CON‐PASIII and CON‐PASIIIM); and 3) subjected to PRT and stored in PAS (PRT‐PASIII and PRT‐PASIIIM). Cell quality variables (pH, swirl, lactate, and glucose), flow cytometry analysis, and adhesive and aggregating functions using a perfusion system were assessed on Days 0, 3, 5, and 7.

RESULTS: All the groups showed a progressive reduction in cell quality variables during storage. Swirl was progressively reduced and better maintained in CON‐PPP. Flow cytometry analysis revealed a moderate reduction in glycoprotein Ib for all study groups on Day 7, being less evident in CON‐PPP. A progressive increase in P‐selectin levels was observed during storage. Perfusion studies demonstrated that PRT‐treated PCs stored in PAS presented similar reactivity with subendothelium than that observed for untreated PCs stored in plasma or in PAS for Day 5. Moderate reductions in cohesive properties in PRT‐PASIII PCs, but not in PRT‐PASIIIM PCs, were observed after 7 days.

CONCLUSIONS: PLT properties were preserved in PRT‐treated concentrates stored in PAS for 5 days. PASIIIM provides a better preservation of adhesive and cohesive functions of PRT‐PCs than PASIII for 7 days of storage. The relevance of in vitro data deserves further clinical investigations.
Blood center practice and education for blood donors with anemia
Authors: Delaney Meghan , Schellhase Kenneth G. , Young Staci , Geiger Susan , Fink Arlene , Mast Alan E.
Published: October 2010

BACKGROUND: Anemia is an early indicator of many diseases, yet blood donors with low hematocrit (Hct) often receive inadequate information about its medical importance. We sought to understand the types of information that are and should be provided to these donors.

STUDY DESIGN AND METHODS: Two companion studies were performed. The first investigated blood center practices for care of donors with low Hct including deferral length, information provided, and cutoff values used when referring donors for medical attention. The second was a randomized prospective pilot study comparing behavior of deferred donors receiving an “older” pamphlet providing a list of iron‐rich foods or a “newer” pamphlet providing descriptions of common causes of anemia and advice for seeking medical attention.

RESULTS: More than 70% of centers defer donors for 1 day. Only 6% defer donors for more than 2 weeks. Most centers provide written and/or verbal information about low Hct. Only 35% have a cutoff value defining significant anemia that requires additional medical attention. In the study of donors with low Hct, significant disease was identified within 3 months after deferral in 2 of 104 subjects: metastatic lung cancer and acute lymphocytic leukemia. Only donors receiving the newer pamphlet reported that it “definitely improved” their ability to speak with their doctor about anemia.

CONCLUSIONS: The diagnosis of anemia in blood donors may be an indicator of significant undiagnosed disease. There are wide variations in how centers care for and educate donors with anemia. Donors with anemia should be provided improved and consistent educational information.
Income Inequality and Partisan Voting in the United States*
Authors: Gelman Andrew , Kenworthy Lane , Su Yu‐Sung
Published: October 2010

Objectives.Income inequality in the United States has risen during the past several decades. Has this produced an increase in partisan voting differences between rich and poor?

Methods.We examine trends from the 1940s through the 2000s in the country as a whole and in the states.

Results.We find no clear relation between income inequality and class‐based voting.

Conclusions.Factors such as religion and education result in a less clear pattern of class‐based voting than we might expect based on income inequality alone.
Can Institutional Networks Mitigate Labor Market Disadvantages? Evidence from College Summer Job Searches*
Authors: Fischer Mary J.
Published: October 2010

Objective. This study examines whether the use of institutional (school‐based) networks may help students from disadvantaged backgrounds secure summer employment opportunities that are on a par with those of their more advantaged classmates who may possess more resource‐rich personal and familial networks.

Methods. The study draws on unique data from the National Longitudinal Survey of Freshmen to examine the strategies that a national representative sample of nearly 4,000 white, black, Asian, and Hispanic students on 28 campuses used to obtain summer employment and the characteristics of these summer jobs. Multinomial logistic regression techniques are applied to examine the types of contacts students used and jobs they found, while OLS regression is employed to examine the wages and occupational prestige of summer positions.

Results. The study reveals that students who obtained their summer jobs through institutional contacts had significantly higher earnings and held positions with higher occupational prestige than students using most other methods (controlling for race/ethnicity, prior work experience, and parental education). I also found that minority students are at least as likely as white students to draw on these institutional networks. In addition, there were no differences by SES, suggesting that this type of capital is both accessible and accessed by a wide range of students.

Conclusions. This study provides evidence that summer jobs obtained through institutional networks are more likely to be in desirable sectors, on average pay better, and have higher occupational prestige scores than jobs obtained by most other methods.