bluuebunny/crossref_metadata_2025 huggingface dataset:
Designing evidence‐based treatments for youth with multiple and complex needs: a modular practice elements approach
Authors: Fay Mitchell Penelope
Published: August 2012

Purpose

Young people receiving services for substance use problems often experience high rates of other psychosocial problems in addition to mental disorders. This has implications for design of effective interventions. There is a lack of concisely organised practical information to help organisations serving this population establish contextually relevant and rigorous approaches to the design of evidence‐based interventions. This paper aims to focus on these issues.

Design/methodology/approach

Drawing on literature from clinical and implementation science, this paper describes a new approach to the development and implementation of evidence‐based practice (EBP). Contributions of innovators, early adopters, evaluators, and other scholars are reviewed and synthesized.

Findings

Traditional approaches to EBP relying on manualised programs targeting discrete diagnoses have not yielded meaningful progress in the dissemination of EBP to services that specialise in treatment and support for young people experiencing complex psychosocial needs. Recent initiatives are moving away from reliance on manualised programs and adopting a modular practice elements approach that enables maximum flexibility in responding to the unique needs of individual clients. This approach has potential to mitigate barriers to implementation of EBP in resource poor environments.

Originality/value

The complexity of needs presented by young people with dual mental health and substance use problems is increasingly recognised, but there is little information available that supports the formulation evidence‐based interventions that directly address this complexity. This paper applies knowledge from research to the practical challenges faced by practice leaders in real‐world services.
Bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukaemia: updated results of a randomized phase III trial
Authors: Knauf Wolfgang U. , Lissitchkov Toshko , Aldaoud Ali , Liberati Anna M. , Loscertales Javier , Herbrecht Raoul , Juliusson Gunnar , Postner Gerhard , Gercheva Liana , Goranov Stefan , Becker Martin , Fricke Hans‐Joerg , Huguet Francoise , Del Giudice Ilaria , Klein Peter , Merkle Karlheinz , Montillo Marco
Published: August 2012

The efficacy of bendamustine versus chlorambucil in a phase III trial of previously untreated patients with Binet stage B/C chronic lymphocytic leukaemia (CLL) was re‐evaluated after a median observation time of 54 months in May 2010. Overall survival (OS) was analysed for the first time. At follow‐up, investigator‐assessed complete response (CR) rate (21·0% vs 10·8%), median progression‐free survival (21·2 vs 8·8 months; P < 0·0001; hazard ratio 2·83) and time to next treatment (31·7 vs 10·1 months; P < 0·0001) were improved for bendamustine over chlorambucil. OS was not different between groups for all patients or those ≤65 years, >65 years, responders and non‐responders. However, patients with objective response or a CR experienced a significantly longer OS than non‐responders or those without a CR. Significantly more patients on chlorambucil progressed to second/further lines of treatment compared with those on bendamustine (78·3% vs 63·6%; P = 0·004). The benefits of bendamustine over chlorambucil were achieved without reducing quality of life. In conclusion, bendamustine is significantly more effective than chlorambucil in previously untreated CLL patients, with the achievement of a CR or objective response appearing to prolong OS. Bendamustine should be considered as a preferred first‐line option over chlorambucil for CLL patients ineligible for fludarabine, cyclophosphamide and rituximab.
Genome‐wide Inference of Transcription Factor–DNA Binding Specificity in Cell Regeneration Using a Combination Strategy
Authors: Wang Xiaofeng , Zhang Aiqun , Ren Weizheng , Chen Caiyu , Dong Jiahong
Published: August 2012

The cell growth, development, and regeneration of tissue and organ are associated with a large number of gene regulation events, which are mediated in part by transcription factors (TFs) binding to cis‐regulatory elements involved in the genome. Predicting the binding affinity and inferring the binding specificity of TF–DNA interactions at the genomic level would be fundamentally helpful for our understanding of the molecular mechanism and biological implication underlying sequence‐specific TF–DNA recognition. In this study, we report the development of a combination method to characterize the interaction behavior of a 11‐mer oligonucleotide segment and its mutations with the Gcn4p protein, a homodimeric, basic leucine zipper TF, and to predict the binding affinity and specificity of potential Gcn4p binders in the genome‐wide scale. In this procedure, a position‐mutated energy matrix is created based on molecular modeling analysis of native and mutated Gcn4p–DNA complex structures to describe the position‐independent interaction energy profile of Gcn4p with different nucleotide types at each position of the oligonucleotide, and the energy terms extracted from the matrix and their interactives are then correlated with experimentally measured affinities of 19 268 distinct oligonucleotides using statistical modeling methodology. Subsequently, the best one of built regression models is successfully applied to screen those of potential high‐affinity Gcn4p binders from the complete genome. The findings arising from this study are briefly listed below: (i) The 11 positions of oligonucleotides are highly interactive and non‐additive in contribution to Gcn4p–DNA binding affinity; (ii) Indirect conformational effects upon nucleotide mutations as well as associated subtle changes in interfacial atomic contacts, but not the direct nonbonded interactions, are primarily responsible for the sequence‐specific recognition; (iii) The intrinsic synergistic effects among the sequence positions of oligonucleotides determine Gcn4p–DNA binding affinity and specificity; (iv) Linear regression models in conjunction with variable selection seem to perform fairly well in capturing the internal dependences hidden in the Gcn4p–DNA system, albeit ignoring nonlinear factors may lead the models to systematically underestimate and overestimate high‐ and low‐affinity samples, respectively.
Survival analysis
Authors: Flynn Robert
Published: August 2012

Aims and objectives.  This paper describes when and why survival analysis is used and describes the use and interpretation of the techniques most commonly encountered in medical literature. This is performed using examples taken from core medical journals.

Background.  Survival analysis is widely used in clinical and epidemiological research: in randomised clinical trials for comparing the efficacy of treatments and in observational (non‐randomised) research to determine and test the existence of epidemiological association.

Design.  This paper introduces the principles, practice and terminology of survival analysis.

Methods.  References are made to examples from open‐access medical journals.

Results.  Survival analysis is a well‐established series of methodologies that are widely encountered in medical literature for both observational and randomised studies.

Conclusions.  Survival analysis represents a more efficient use of clinical data than other forms of analysis which rely on fixed time periods. One of the most widely used techniques is that developed by Kaplan and Meier. This involves the creation of life tables and the plotting of survival curves with comparison made between two or more groups. The log‐rank test is commonly used to establish whether there is a statistically significant difference between these groups. The Multivariate Cox proportional hazards extend this approach to give an estimate of effect size (the Hazards Ratio) and can adjust for any potential confounding variables. In this model, the assumption of proportional hazards is of key importance and should always be checked. More advanced techniques are the use of time‐dependent variables and the less widely used parametric survival techniques. Care should always be taken when considering the assumptions involved when using such methods.

Relevance to clinical practice.  As survival analysis is widely used in clinical research, it is important that readers can critically evaluate the use of this technique.
Can we trust the new generation of infrared tympanic thermometers in clinical practice?
Authors: Haugan Berit , Langerud Anne K , Kalvøy Håvard , Frøslie Kathrine F , Riise Else , Kapstad Heidi
Published: August 2012

Aims and objectives.  To explore the reliability and validity of the new generation of infrared tympanic thermometers, comparing with rectal and core temperature, and to decide their applicability to clinical practice.

Background.  Digital contact thermometers for rectal measurements and infrared tympanic thermometers are the most common way to measure patients’ temperature. Previous studies of the infrared tympanic thermometers revealed misdiagnosis, and validity of early models was questioned.

Design.  Reliability and validity study.

Methods.  Temperature was measured with two infrared tympanic thermometers brands in both ears and compared with rectal temperature twice a day at the ward (n = 200). At the intensive care unit, patients (n = 42) underwent the same measurement procedures every fourth hour for 24 hours. In addition, core temperature was measured. Statistical analyses included descriptive and mixed models analyses.

Results.  Ward: Infrared tympanic thermometers measured the temperature lower than the rectal temperature. Descriptive statistics indicate higher variation in temperature measurements made in the ear. No statistically significant difference in temperature was found for left ear vs. right ear. Intensive care unit: The mean rectal temperature was higher than the mean core and ear temperature. Mixed models analyses of the temperatures at the ward and the intensive care unit showed the same overall trends, but with less discrepancy between the two infrared tympanic thermometers brands, compared with the rectal temperature. Only rectal temperature measurements differed significantly from the core temperature.

Conclusion.  Our study shows good reliability using the new generation of infrared tympanic thermometers. We found good agreement between core and infrared tympanic thermometers at the intensive care unit, but the measuring inaccuracy for infrared tympanic thermometers was greater than expected.

Relevance to clinical practice.  The new generation of infrared tympanic thermometers may be used in clinical practice, but it is important to do repeatedly measurements if there is discrepancy between the temperature and the observation of the patient condition.
Assessment of nutritional status and meal‐related situations among patients with chronic obstructive pulmonary disease in Primary health care – obese patients; a challenge for the future
Authors: Odencrants Sigrid , Theander Kersti
Published: August 2012

Aims and objectives.  To describe nutritional status, meal related situations, food habits and food preferences of patients with chronic obstructive pulmonary disease (COPD) in a Primary health care (PHC) setting.

Background.  To date, guidelines have mainly focused on underweight patients with COPD, as a low body mass index (BMI) is a risk factor for mortality. However, in recent years there has been an increase in the number of overweight patients with COPD, and therefore nutritional management must be developed to cover problems related to both under and overweight.

Design.  Descriptive.

Methods.  One hundred and three patients from PHC centres representing COPD stages 2 and 3 were included. The Mini Nutritional Assessment (MNA) was used to collect nutritional status data while semi‐structured interviews provided information on food and meal related situations.

Results.  Mean age was 69 (±5) years and 45% were women. Among all patients mean BMI was 27 and 14% had a BMI ≤ 21 kg/m2. More women (31%) than men (26%) had a BMI ≥ 30 kg/m2. According to the MNA screening score, 86% of the patients were assessed as normal or not at risk of malnutrition. The total MNA assessment score revealed that 10 patients were at risk of malnutrition or malnourishment. Problems with meal related situations were mostly associated with eating, and only a small number reported difficulties with shopping or preparing food.

Conclusions.  In PHC, more patients with COPD were obese than malnourished and their self‐reported nutritional status was not always accurate.

Relevance to clinical practice.  It is challenging to identify the patient’s nutritional status, individualize nutritional care and educate obese patients with COPD at PHC centres. It is necessary to develop screening instruments to assess the risk of both obesity and malnutrition.
Field models for the prediction of leaf infection and latent period of Fusicladium oleagineum on olive based on rain, temperature and relative humidity
Authors: Roubal C. , Regis S. , Nicot P. C.
Published: August 2012

Although much is known about the effect of climatic conditions on the development of peacock leaf spot of olive, field‐operational models predicting disease outbreaks are lacking. With the aim of developing such models, a 10‐year survey was conducted to relate leaf infection to climate parameters that can be easily monitored in the field. As outbreaks of disease are known to be linked to rain, models were evaluated for their ability to predict whether infection would occur following a rain event, depending on air temperature and duration of relative humidity above 85%. A total of 134 rain events followed by confirmed leaf infection and 191 rain events not followed by detectable infection were examined. The field data were adequately fitted (both specificity and sensitivity >0·97) with either a multilayer neural network or with two of six tested regression models describing high boundary values of high humidity duration, above which no infection occurred over the temperature range, and low boundary values below which no infection occurred. The data also allowed the selection of a model successfully relating the duration of latent period (time between infection and the first detection of leaf spots) as a function of air temperature after the beginning of rain (R2 > 0·98). The predictive abilities of these models were confirmed during 2 years of testing in commercial olive orchards in southern France. They should thus provide useful forecasting tools for the rational application of treatments and foster a reduction in fungicide use against this major disease of olive.
The reliability of leaf bioassays for predicting disease resistance on fruit: a case study on grapevine resistance to downy and powdery mildew
Authors: Calonnec A. , Wiedemann‐Merdinoglu S. , Delière L. , Cartolaro P. , Schneider C. , Delmotte F.
Published: August 2012

This study was designed to assess the reliability of grapevine leaf bioassays for predicting disease resistance on fruit in the field. The efficacy of various grapevine quantitative trait loci (QTLs) for conferring resistance to downy and powdery mildew was evaluated in bioassays and in a 2‐year field experiment for downy mildew. The resistance genes studied were inherited from Muscadinia rotundifolia (Rpv1 and Run1) and from American Vitis species through cv. Regent (QTLRgP and QTLRgD). In bioassays, genotypes carrying Run1 blocked powdery mildew development at early stages. Genotypes combining Run1 with QTLRgP displayed no greater level of resistance. For downy mildew, genotypes carrying Rpv1 and/or QTLRgD were more resistant than the susceptible cv. Merlot, and showed a high level of leaf resistance in the field (<10% severity). Disease levels on bunches were much higher than those on leaves, with a high variability between Rpv1 genotypes (1–48%). A Bayesian decision theory framework predicted that an OIV‐452 threshold of 5 in leaf bioassays allowed accurate selection of grapevine genotypes (P = 0·83) with satisfactory disease severity on bunches. Therefore, this study validates that the use of early bioassays on leaves, as currently performed by grapevine breeders, ensures a satisfactory level of resistance to downy mildew of bunches in the field.
Clonal populations of Leptosphaeria maculans contaminating cabbage in Mexico
Authors: Dilmaghani A. , Gout L. , Moreno‐Rico O. , Dias J. S. , Coudard L. , Castillo‐Torres N. , Balesdent M.‐H. , Rouxel T.
Published: August 2012

The race structure and genotypic diversity of four Leptosphaeria maculans populations isolated from Brassica oleracea (broccoli, cauliflower, cabbage, etc.) in central Mexico (Aguascalientes, Guanajuato and Zacatecas states) were analysed. Race structure was characterized by an unusually low diversity at three locations out of four. Fourteen minisatellite markers revealed a high proportion of repeated multilocus genotypes in these populations, combined with a significant linkage disequilibrium and strong clonal fraction (65–87%). The occurrence of the mating‐type idiomorphs always significantly departed from the 1:1 proportion expected in the case of random mating. Each population thus consists of a few (four to nine) multilocus genotypes which are specific to each location. These data strongly support the hypothesis of exclusive, or a high rate of, clonal multiplication. Comparison of cropping practices between B. oleracea and B. napus indicate that the shift in reproductive behaviour of the fungus is chiefly man‐mediated.
Induced resistance to Verticillium longisporum in Brassica napus by β‐aminobutyric acid
Authors: Kamble A. , Koopmann B. , von Tiedemann A.
Published: August 2012

A preinoculative soil drench application of 0·5 mm β‐aminobutyric acid (BABA) significantly inhibited colonization of oilseed rape (Brassica napus, susceptible cultivar Falcon) by Verticillium longisporum and also prevented plant stunting caused by the pathogen. To better understand the defence responses induced by BABA, the presence of occlusions in the plant hypocotyl, levels of salicylic acid (SA) and hydrogen peroxide (H2O2), phenylalanine ammonia lyase (PAL) activity and expression of PR‐1 and PDF1.2 genes were examined. Transverse sections through the hypocotyl region of BABA‐treated plants showed clear vessels surrounded by phenol‐storing cells, in contrast to numerous obstructed vessels in water‐treated plants, in response to the pathogen. A significant increase in SA levels was observed in the hypocotyls of both water‐ and BABA‐treated plants in response to the pathogen; however, SA levels were unrelated to disease resistance. The level of H2O2 decreased in both treatments in response to the pathogen. A significant increase in PAL activity was observed in hypocotyl tissues of BABA‐treated plants. The expression patterns of PR‐1 and PDF1.2 were similar in the two treatments in response to the pathogen, indicating no involvement of these genes in resistance. The results indicate a similar organ specificity of the plant hypocotyl for chemically induced internal resistance as for genotype‐related resistance, two phenomena which, however, are based on contrasting cytological responses in the vascular tissues. Nonetheless, evidence is provided that the activity of the phenylpropanoid pathway plays a crucial role in both types of resistance.
Potential Implication of Activating Killer Cell Immunoglobulin‐Like Receptor and HLA in Onset of Pulmonary Tuberculosis
Authors: Lu C. , Bai X. L. , Shen Y. J. , Deng Y. F. , Wang C. Y. , Fan G. , Chu J. X. , Zhao S. M. , Zhang B. C. , Zhao Y. R. , Zhang C. Z. , Ye H. , Lu Z. M.
Published: August 2012

Killer cell immunoglobulin‐like receptor (KIR) and human leucocyte antigen (HLA) play crucial role in maintaining immune homoeostasis and controlling immune responses. To investigate the influence of KIR and HLA‐C ligands on the risk of pulmonary tuberculosis (PTB), we studied 200 patients who were confirmed to have PTB and 200 healthy controls on the different frequencies of KIR and HLA‐C ligands. Genotyping of these genes was conducted by sequence‐specific primer polymerase chain reaction (SSP‐PCR) method. Gene frequencies were compared between PTB group and the control group by χ2 test, and P < 0.05 was regarded as statistically significant. As a result, the frequency of KIR genotype A/B was increased in PTB than controls but A/A was decreased. Moreover, striking differences were observed in the frequencies of HLA‐Cw*08 between the two groups. Besides, the frequencies of ‘2DL2/3 with C1’ in PTB were increased compared with control group. In addition, individuals with no KIR2DS3 and no Cw*08 were higher in controls than in PTB. KIR2DS1 was increased in PTB when HLA‐C group 2 alleles were missing. In conclusion, KIR and HLA‐C gene polymorphisms were related to susceptibility to PTB.
High Non‐Specific T Lymphocyte Response to the Adjuvanted H1N1 Vaccine in Comparison with the H1N1/H3N2/B‐Brisbane Vaccine without Adjuvant
Authors: Korošec P. , Petrovec M. , Lainščak M. , Meško P. , Šilar M. , Košnik M.
Published: August 2012

Shortly after the report of pandemic 2009 influenza A (H1N1), vaccine manufacturers, in conjunction with public agencies, started developing a H1N1 vaccine. In 2009, various approaches were implemented around the globe. The United States and Australia finally approved only non‐adjuvanted H1N1 influenza vaccines, whereas Canada and the EU also approved adjuvanted vaccines. In 2010, seasonal influenza vaccine without adjuvant was again widely accepted in both hemispheres. The addition of adjuvant to the vaccine enhances the immunogenity of the vaccine in the presence of a relatively low amount of antigen. However, it might also induce undesirable non‐specific immune response. For this reason, we conducted a prospective observational study to monitor T cell absolute count and H1N1‐specific immunogenicity after 2009 and 2010 immunization. Fourteen healthy volunteers received the monovalent H1N1 AS03 adjuvanted influenza vaccine (3.5 μg of H1N1 and squalene‐based adjuvant) in October 2009. The immunization was associated with a significant increase in T lymphocyte absolute count (P < 0.0001), reaching abnormal values in 57% of subjects. During this period, none of the subject showed any manifestation of severe viral infection or inflammation. Acute infection by CMV or EBV viruses was also excluded. In October 2010, the same subjects received a seasonal non‐adjuvanted influenza vaccine (15 μg of each: H1N1, H3N2, and B‐Brisbane). However, after 2010 immunization, no change in T lymphocyte absolute count was observed. H1N1‐induced immunogenicity was good for both vaccines. Our results suggest a pronounced non‐specific T cell response after AS03‐adjuvanted 2009 H1N1 vaccination.
The requirement for recombination factors differs considerably between different pathways of homologous double‐strand break repair in somatic plant cells
Authors: Roth Nadine , Klimesch Jacqueline , Dukowic‐Schulze Stefanie , Pacher Michael , Mannuss Anja , Puchta Holger
Published: August 2012

In recent years, multiple factors involved in DNA double‐strand break (DSB) repair have been characterised in Arabidopsis thaliana. Using homologous sequences in somatic cells, DSBs are mainly repaired by two different pathways: synthesis‐dependent strand annealing (SDSA) and single‐strand annealing (SSA). By applying recombination substrates in which recombination is initiated by the induction of a site‐specific DSB by the homing endonuclease I‐SceI, we were able to characterise the involvement of different factors in both pathways. The nucleases MRE11 and COM1, both involved in DSB end processing, were not required for either SDSA or SSA in our assay system. Both SDSA and SSA were even more efficient without MRE11, in accordance with the fact that a loss of MRE11 might negatively affect the efficiency of non‐homologous end joining. Loss of the classical recombinase RAD51 or its two paralogues RAD51C and XRCC3, as well as the SWI2/SNF2 remodelling factor RAD54, resulted in a drastic deficiency in SDSA but had hardly any influence on SSA, confirming that a strand exchange reaction is only required for SDSA. The helicase FANCM, which is postulated to be involved in the stabilisation of recombination intermediates, is surprisingly not only needed for SDSA but to a lesser extent also for SSA. Both SSA and SDSA were affected only weakly when the SMC6B protein, implicated in sister chromatid recombination, was absent, indicating that SSA and SDSA are in most cases intrachromatid recombination reactions.
A new HLA‐C*07:244 allele identified by sequence‐based typing in a Korean individual
Authors: Cho D. , Jang M. J. , Yoon C. E. , Kwon O. J. , Shin M. G.
Published: August 2012

The C*07:244 changes single nucleotide of C*07:02:01 at codon 75 (CGA → CAA), Arg to Gln.
HLA‐DQ association and allele competition in Chinese narcolepsy
Authors: Han F. , Lin L. , Li J. , Dong S. X. , An P. , Zhao L. , Liu N. Y. , Li Q. Y. , Yan H. , Gao Z. C. , Faraco J. , Strohl K. P. , Liu X. , Miyadera H. , Mignot E.
Published: August 2012

In Japanese, Koreans and Caucasians, narcolepsy/hypocretin deficiency is tightly associated with the DRB1*15:01‐DQA1*01:02‐DQB1*06:02 haplotype. Studies in African‐Americans suggest a primary effect of DQB1*06:02, but this observation has been difficult to confirm in other populations because of high linkage disequilibrium between DRB1*15:01/3 and DQB1*06:02 in most populations. In this study, we studied human leucocyte antigen (HLA) class II in 202 Chinese narcolepsy patients (11% from South China) and found all patients to be DQB1*06:02 positive. Comparing cases with 103 unselected controls, and 110 and 79 controls selected for the presence of DQB1*06:02 and DRB1*15:01, we found that the presence of DQB1*06:02 and not DRB1*15:01 was associated with narcolepsy. In particular, Southern Chinese haplotypes such as the DRB1*15:01‐DQA1*01:02‐DQB1*06:01 and DRB1*15:01‐DQA1*01:02‐DQB1*05 were not associated with narcolepsy. As reported in Japanese, Koreans, African‐Americans and Caucasians, additional protective effects of DQA1*01 (non‐DQA1*01:02) and susceptibility effects of DQB1*03:01 were observed. These results illustrate the extraordinary conservation of HLA class II effects in narcolepsy across populations and show that DRB1*15:01 has no effect on narcolepsy susceptibility in the absence of DQB1*06:02. The results are also in line with a previously proposed ‘HLA‐DQ allelic competition model’ that involves competition between non‐DQA1*01:02, non‐DQB1*06:02 ‘competent’ (able to dimerize together) DQ1 alleles and the major DQα*01:02/ DQβ*06:02 narcolepsy heterodimer to reduce susceptibility.
Temporary inhibitory tagging at previously attended locations: Evidence from event‐related potentials
Authors: Zhang Yang , Zhou Xiaolin , Zhang Ming
Published: August 2012

Recent studies propose that a mechanism termed “inhibitory tagging” acts upon the processing of the target at the attended location by temporarily blocking the stimulus‐response mapping. Here we combined the cue–target paradigm with the Stroop task and measured event‐related potential (ERP) responses to the color of a color word presented at the previously attended (cued) or unattended (uncued) location. We found that the conflict‐related N450 effect emerged later and had a smaller size at the cued than the uncued location. The overall ERP responses to the target showed lower P1 and N1 amplitude at the cued than the uncued location. Although the P1/N1 effect may reflect deficient perceptual processing of the target, the delay of the N450 suggests that the link between perceptual processing and response activation is temporarily blocked at the previously attended location.
Comparative peptidomics analysis of neural adaptations in rats repeatedly exposed to amphetamine
Authors: Romanova Elena V. , Lee Ji Eun , Kelleher Neil L. , Sweedler Jonathan V. , Gulley Joshua M.
Published: August 2012

Repeated exposure to amphetamine (AMPH) induces long‐lasting behavioral changes, referred to as sensitization, that are accompanied by various neuroadaptations in the brain. To investigate the chemical changes that occur during behavioral sensitization, we applied a comparative proteomics approach to screen for neuropeptide changes in a rodent model of AMPH‐induced sensitization. By measuring peptide profiles with matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry and comparing signal intensities using principal component analysis and variance statistics, subsets of peptides are found with significant differences in the dorsal striatum, nucleus accumbens, and medial prefrontal cortex of AMPH‐sensitized male Sprague–Dawley rats. These biomarker peptides, identified in follow‐up analyses using liquid chromatography and tandem mass spectrometry, suggest that behavioral sensitization to AMPH is associated with complex chemical adaptations that regulate energy/metabolism, neurotransmission, apoptosis, neuroprotection, and neuritogenesis, as well as cytoskeleton integrity and neuronal morphology. Our data contribute to a growing number of reports showing that in addition to the mesolimbic dopamine system, which is the best known signaling pathway involved with reinforcing the effect of psychostimulants, concomitant chemical changes in other pathways and in neuronal organization may play a part in the overall effect of chronic AMPH exposure on behavior.
Association of three different techniques to measure blood pressure in the first trimester with the development of hypertensive disorders of pregnancy
Authors: VOLLEBREGT KARLIJN CORIEN , BOER KEES , VAN DER POST JORIS A. M. , WOLF HANS
Published: August 2012

Objective

It is not known whether automated devices for measuring blood pressure perform better than conventional sphygmomanometry in predicting preeclampsia. This study compares two different automated devices with conventional sphygmomanometry for their association with development of preeclampsia or gestational hypertension.

Design

Prospective observational cohort study.

Setting

University hospital, Amsterdam, the Netherlands.

Population

289 healthy normotensive women of whom 235 were nulliparous and 44 parous with preeclampsia in a previous pregnancy.

Methods

At 8–11 weeks of pregnancy, blood pressure was measured with two different automated devices (continuous finger arterial pressure waveform registration and ambulatory blood pressure monitoring) and with conventional sphygmomanometry.

Main outcome measures

Preeclampsia and gestational hypertension.

Results

Blood pressure in the first trimester, as measured with all three methods, was significantly higher in women who developed preeclampsia or gestational hypertension. After adjustment for previous preeclampsia, the point estimate of the odds ratios for association with later preeclampsia for both automated devices were comparable and higher than for conventional sphygmomanometry; however, differences were not statistically significant. The odds ratio (95% confidence intervals) for every 1 mmHg pressure increase of mean arterial pressure was 1.08 (1.02–1.15) for sphygmomanometry, 1.17 (1.09–1.27) for finger arterial pressure waveform registration, and 1.17 (1.07–1.27) for ambulatory blood pressure monitoring. Results were comparable if preeclampsia and gestational hypertension were analyzed together.

Conclusion

Blood pressure in the first trimester was associated with the development of hypertensive disorders of pregnancy. No significant differences were found between measurements by automatic devices compared with conventional sphygmomanometry.
Prevalence of the HPA‐18w to ‐21w alleles in the Chinese Han population
Authors: Liu Y. , Hong X. , Xu X. , Ying Y. , He J. , Zhu F. , Lv H. , Yan L.
Published: August 2012

Recently, four new platelet alloantigen (HPA) systems HPA‐18w to‐21w were identified. However, genotyping for HPA‐18w to ‐21w alleles was rarely reported. Here, we established a polymerase chain reaction sequence–based typing (PCR‐SBT) method and investigated the distribution of HPA‐18w to ‐21w alleles in the Chinese Han population. The specific primers of HPA‐18w, ‐19w, ‐20w and ‐21w were designed, and the PCR products were bidirectionally sequenced. 855 randomly selected platelet donors were genotyped for HPA‐18w to ‐21w with the PCR‐SBT method. The results showed that all individuals were monomorphic for HPA‐18w to HPA‐20w with a/a homozygous frequency of 1.0 and absence of HPA‐18bw to ‐20bw alleles. The frequencies of the HPA‐21a/21a and HPA‐21a/21b genotypes were 0.981(839/855) and 0.019(16/855), respectively. Seven mutations were confirmed on sequenced region separate from HPA polymorphisms, including ITGA2 (IVS17+48G>A and IVS17+72G>A), ITGA2B (IVS19‐26C>G) and ITGB3 (IVS4+234C>T, IVS11‐19 T>C, IVS11‐104T>C and GT repeats from IVS11‐131 to IVS11‐109). These data will provide useful information for diagnosis, prevention and treatment of alloimmune thrombocytopaenia.
Flowering and Fruiting Patterns in a Subtropical Rain Forest, Taiwan
Authors: Chang‐Yang Chia‐Hao , Lu Chia‐Ling , Sun I‐Fang , Hsieh Chang‐Fu
Published: August 2012

Reproductive patterns of tropical and temperate plants are usually associated with climatic seasonality, such as rainfall or temperature, and with their phylogeny. It is still unclear, however, whether plant reproductive phenology is influenced by climatic factors and/or phylogeny in aseasonal subtropical regions. The plant reproductive phenology of a subtropical rain forest in northern Taiwan (24°45′ N, 121°35′ E) was monitored at weekly intervals during a 7‐yr period (2002–2009). The flowering patterns of 46 taxa and fruiting patterns of 26 taxa were examined and evaluated in relation to climatic seasonality, phylogenetic constraints, and different phenophases. Our results indicated that most of the studied species reproduced annually. Additionally, both community‐wide flowering and fruiting patterns exhibited distinct annual rhythms and varied little among years. The community flowering peak matched seasonal changes in day length, temperature, and irradiance; while the community fruiting peak coincided with an increase in bird richness and the diet‐switching of resident omnivorous birds. In addition, phylogenetically closely related species tended to reproduce during the same periods of a year. Neither the mean flowering dates nor seasonal variation in solar radiation, however, was related to the fruit development times. Our results indicate the importance of abiotic, biotic, and evolutionary factors in determining the reproductive phenology in this subtropical forest.
Effects of subconjunctival bevacizumab on corneal neovascularization: results of a prospective study
Authors: BENAYOUN Y , ADENIS JP , CASSE G , FORTE R , ROBERT PY
Published: August 2012

Purpose To evaluate the effect of subconjunctival bevacizumab injections in patients with corneal neovascularization resulting from different ocular surface disorders.

Methods Prospective case series. Fourteen eyes of 13 patients with corneal neovascularization caused by different ocular surface disorders, such as healed corneal ulcers, long‐standing chronic inflammatory diseases and corneal ischaemia secondary to burn were included. All eyes received a single subconjunctival injection of 2.5 mg (0.1 ml) bevacizumab. Morphological changes in neovascularization were evaluated during 3 months using slit‐lamp biomicroscopy, corneal digital photography, and computed‐assisted semi‐automatic analysis of corneal neovascularization area.

Results Recession of corneal vessels was observed in all eyes at 1 week post‐injection. The surface of the neovascular tree continued to decrease noticeably for one month and then increased again for the remainder of the follow‐up period. The corneal neovascularization area amounted to 12.14± 4.38% of the corneal surface pre‐injection, compared with 9.10± 3.16% post‐injection (p=0.02), reflecting a mean decrease in corneal neovascularization of 25 %. No local or systemic adverse events possibly related to subconjunctival bevacizumab injection were observed.

Conclusion Short‐term results suggest that subconjunctival bevacizumab can be used safely and effectively for corneal neovascularization resulting from different ocular surface disorders, providing an additional strategy to improve success of corneal grafts.
Corporate Governance Reform and Executive Incentives: Implications for Investments and Risk Taking
Authors: Cohen Daniel A. , Dey Aiyesha , Lys Thomas z.
Published: August 2012

We investigate the mechanism through which the Sarbanes Oxley Act (SOX) was associated with changes in corporate investment strategies. We document that the passage of the governance regulations in SOX was followed by a significant decline in pay‐performance sensitivity (Delta) and incentives to take risk (Vega) in CEOs' compensation contracts. These changes in compensation contracts are related to a decline in investments, including research and development expenditures, capital investments and acquisitions. Moreover, consistent with the rules in SOX directly affecting CEOs' incentives to take risk, we document that the decline in investments exceeds the amount that would be expected from changes in compensation packages alone. Finally, we also find evidence that the changes in investments are related to lower operating performances of firms, suggesting that these changes were costly to investors. Our evidence speaks to the debate on how corporate governance regulation interacts with firms' and managers' incentives, and ultimately affects corporate operating and investment strategies. Our study suggests that one indirect cost of such regulations in SOX is the significant reductions in corporate risk‐taking activities in the post‐SOX period. The changes in investments were in part due to changes in executive compensation contracts and in part related to increased executives' personal costs of engaging in risky activities.
Proxy Position Prediction Based Continuous Local Patch for Smooth Haptic Rendering
Authors: Liu Yong , Chou Wusheng , Yan Shumin
Published: August 2012

The edge effect is a problem that has to be tackled when performing haptic interaction with discontinuous primitives. In this paper, an innovated algorithm is designed to render a smooth haptic feedback force with a locally constructed C1 continuous Gregory patch. The continuous Gregory patch is generated from n-sided polygon, which is determined by a real-time contact region prediction method. The contact region prediction algorithm, derived from the dynamic model of the haptic device, is able to deal with the inconsistency of the local nearest point and global nearest point when obtaining the potential contact region. The parametric patch can be achieved in three steps employing boundary generation, height model interpolation, and Gregory patch construction. For a better shape preserving character, the height model of the contact region is respected by the parametric Gregory patch construction algorithm. The generated patch is continuous on boundaries and can render continuous feedback force as the proxy point transits between different patches. Since the presented scheme needs fewer primitives than conventional method, it consumes less memory and runs more efficiently in computation. The experimental results have shown that the smooth haptic force can be achieved with the proposed method. Meanwhile, the motion predictor also presents a good performance in the validating experiment.
Effect of Inorganic and Organic Ligands on the Bioavailability of Methylmercury as Determined by Using a
mer-lux
Bioreporter
Authors: Ndu Udonna , Mason Robert P. , Zhang Huan , Lin Senjie , Visscher Pieter T.
Published: August 2012

A
mer-lux
bioreporter was constructed to assess the bioavailability of methylmercury [CH
3
Hg(II)] in
Escherichia coli
. The bioreporter was shown to be sensitive, with a detection limit of 2.5 nM CH
3
Hg(II), and was used to investigate the effects of chlorides, humic acids, and thiols on the bioavailability of CH
3
Hg(II) in
E. coli
. It was found that increasing the concentration of chlorides resulted in an increase in CH
3
Hg(II) bioavailability, suggesting that there was passive diffusion of the neutral complex (CH
3
HgCl
0
). Humic acids were found to reduce the bioavailability of CH
3
Hg(II) in varying degrees. Complexation with cysteine resulted in increased bioavailability of CH
3
Hg(II), while assays with equivalent concentrations of methionine and leucine had little or no effect on bioavailability. The mechanism of uptake of the mercurial-cysteine complexes is likely not passive diffusion but could result from the activities of a cysteine transport system. The bioavailability of CH
3
Hg(II) decreased with increasing glutathione concentrations.
High-Level Production of the Industrial Product Lycopene by the Photosynthetic Bacterium Rhodospirillum rubrum
Authors: Wang Guo-Shu , Grammel Hartmut , Abou-Aisha Khaled , Sägesser Rudolf , Ghosh Robin
Published: August 2012

The biosynthesis of the major carotenoid spirilloxanthin by the purple nonsulfur bacterium
Rhodospirillum rubrum
is thought to occur via a linear pathway proceeding through phytoene and, later, lycopene as intermediates. This assumption is based solely on early chemical evidence (B. H. Davies, Biochem. J. 116:93–99, 1970). In most purple bacteria, the desaturation of phytoene, catalyzed by the enzyme phytoene desaturase (CrtI), leads to neurosporene, involving only three dehydrogenation steps and not four as in the case of lycopene. We show here that the chromosomal insertion of a kanamycin resistance cassette into the
crtC-crtD
region of the partial carotenoid gene cluster, whose gene products are responsible for the downstream processing of lycopene, leads to the accumulation of the latter as the major carotenoid. We provide spectroscopic and biochemical evidence that
in vivo
, lycopene is incorporated into the light-harvesting complex 1 as efficiently as the methoxylated carotenoids spirilloxanthin (in the wild type) and 3,4,3′,4′-tetrahydrospirilloxanthin (in a
crtD
mutant), both under semiaerobic, chemoheterotrophic, and photosynthetic, anaerobic conditions. Quantitative growth experiments conducted in dark, semiaerobic conditions, using a growth medium for high cell density and high intracellular membrane levels, which are suitable for the conventional industrial production in the absence of light, yielded lycopene at up to 2 mg/g (dry weight) of cells or up to 15 mg/liter of culture. These values are comparable to those of many previously described
Escherichia coli
strains engineered for lycopene production. This study provides the first genetic proof that the
R. rubrum
CrtI produces lycopene exclusively as an end product.
Sugarcane Growth Promotion by the Endophytic Bacterium Pantoea agglomerans 33.1
Authors: Quecine M. C. , Araújo W. L. , Rossetto P. B. , Ferreira A. , Tsui S. , Lacava P. T. , Mondin M. , Azevedo J. L. , Pizzirani-Kleiner A. A.
Published: August 2012

The promotion of sugarcane growth by the endophytic
Pantoea agglomerans
strain 33.1 was studied under gnotobiotic and greenhouse conditions. The green fluorescent protein (GFP)-tagged strain
P. agglomerans
33.1::pNKGFP was monitored
in vitro
in sugarcane plants by microscopy, reisolation, and quantitative PCR (qPCR). Using qPCR and reisolation 4 and 15 days after inoculation, we observed that GFP-tagged strains reached similar density levels both in the rhizosphere and inside the roots and aerial plant tissues. Microscopic analysis was performed at 5, 10, and 18 days after inoculation. Under greenhouse conditions,
P. agglomerans
33.1-inoculated sugarcane plants presented more dry mass 30 days after inoculation. Cross-colonization was confirmed by reisolation of the GFP-tagged strain. These data demonstrate that 33.1::pNKGFP is a superior colonizer of sugarcane due to its ability to colonize a number of different plant parts. The growth promotion observed in colonized plants may be related to the ability of
P. agglomerans
33.1 to synthesize indoleacetic acid and solubilize phosphate. Additionally, this strain may trigger chitinase and cellulase production by plant roots, suggesting the induction of a plant defense system. However, levels of indigenous bacterial colonization did not vary between inoculated and noninoculated sugarcane plants under greenhouse conditions, suggesting that the presence of
P. agglomerans
33.1 has no effect on these communities. In this study, different techniques were used to monitor 33.1::pNKGFP during sugarcane cross-colonization, and our results suggested that this plant growth promoter could be used with other crops. The interaction between sugarcane and
P. agglomerans
33.1 has important benefits that promote the plant's growth and fitness.
Improvement of Crystal Solubility and Increasing Toxicity against Caenorhabditis elegans by Asparagine Substitution in Block 3 of Bacillus thuringiensis Crystal Protein Cry5Ba
Authors: Wang Fenshan , Liu Yingying , Zhang Fengjuan , Chai Lujun , Ruan Lifang , Peng Donghai , Sun Ming
Published: August 2012

The crystal proteins from
Bacillus thuringiensis
are widely used for their specific toxicity against insects and nematodes. The highly conserved sequence blocks play an important role in Cry protein stability and flexibility, the basis of toxicity. The block 3 in Cry5Ba subfamily has a shorter sequence (only 12 residues) and more asparagine residues than that of others which harbor about 48 residues but only one asparagine. Based on the theoretical structure model of Cry5Ba, all three asparagines in block 3 are closely located in the interface of putative three domains, implying their probable importance in structure and function. In this study, all three asparagines in Cry5Ba2 block 3 were individually substituted with alanine by site-directed mutagenesis. The wild-type and mutant proteins were overexpressed and crystallized in acrystalliferous
B. thuringiensis
strain BMB171. However, the crystals formed in one of the mutants, designated N586A, abnormally disappeared and dissolved into the culture supernatant once the sporulation cells lysed, whereas the Cry5Ba crystal and the other mutant crystals were stable. The mutant N586A crystal, isolated from sporulation cells by the ultrasonic process, was found to be easily dissolved at wide range of pH value (5.0 to 10.0). Moreover, the toxicity assays showed that the mutant N586A exhibited nearly 9-fold-higher activity against nematodes and damaged the host's intestine more efficiently than the native Cry5Ba2. These data support the presumption that the amide residue Asn586 at the interface of domains might adversely affect the protein flexibility, solubility and resultant toxicity of Cry5Ba.