bluuebunny/crossref_metadata_2025 huggingface dataset:
Middle and later Pleistocene hominins in Africa and Southwest Asia
Authors: Rightmire G. Philip
Published: July 2009

Approximately 700,000 years ago,
Homo erectus
in Africa was giving way to populations with larger brains accompanied by structural adjustments to the vault, cranial base, and face. Such early Middle Pleistocene hominins were not anatomically modern. Their skulls display strong supraorbital tori above projecting faces, flattened frontals, and less parietal expansion than is the case for
Homo sapiens
. Postcranial remains seem also to have archaic features. Subsequently, some groups evolved advanced skeletal morphology, and by
ca.
200,000 years ago, individuals more similar to recent humans are present in the African record. These fossils are associated with Middle Stone Age lithic assemblages and, in some cases, Acheulean tools. Crania from Herto in Ethiopia carry defleshing cutmarks and superficial scoring that may be indicative of mortuary practices. Despite these signs of behavioral innovation, neither the Herto hominins, nor others from Late Pleistocene sites such as Klasies River in southern Africa and Skhūl/Qafzeh in Israel, can be matched in living populations. Skulls are quite robust, and it is only after ≈35,000 years ago that people with more gracile, fully modern morphology make their appearance. Not surprisingly, many questions concerning this evolutionary history have been raised. Attention has centered on systematics of the mid-Pleistocene hominins, their paleobiology, and the timing of dispersals that spread
H. sapiens
out of Africa and across the Old World. In this report, I discuss structural changes characterizing the skulls from different time periods, possible regional differences in morphology, and the bearing of this evidence on recognizing distinct species.
Stable isotope dietary analysis of the Tianyuan 1 early modern human
Authors: Hu Yaowu , Shang Hong , Tong Haowen , Nehlich Olaf , Liu Wu , Zhao Chaohong , Yu Jincheng , Wang Changsui , Trinkaus Erik , Richards Michael P.
Published: July 2009

We report here on the isotopic analysis of the diet of one of the oldest modern humans found in Eurasia, the Tianyuan 1 early modern human dating to ≈40,000 calendar years ago from Tianyuan Cave (Tianyuandong) in the Zhoukoudian region of China. Carbon and nitrogen isotope analysis of the human and associated faunal remains indicate a diet high in animal protein, and the high nitrogen isotope values suggest the consumption of freshwater fish. To confirm this inference, we measured the sulfur isotope values of terrestrial and freshwater animals around the Zhoukoudian area and of the Tianyuan 1 human, which also support the interpretation of a substantial portion of the diet from freshwater fish. This analysis provides the direct evidence for the consumption of aquatic resources by early modern humans in China and has implications for early modern human subsistence and demography.
Sharing global CO
2
emission reductions among one billion high emitters
Authors: Chakravarty Shoibal , Chikkatur Ananth , de Coninck Heleen , Pacala Stephen , Socolow Robert , Tavoni Massimo
Published: July 2009

We present a framework for allocating a global carbon reduction target among nations, in which the concept of “common but differentiated responsibilities” refers to the emissions of individuals instead of nations. We use the income distribution of a country to estimate how its fossil fuel CO
2
emissions are distributed among its citizens, from which we build up a global CO
2
distribution. We then propose a simple rule to derive a universal cap on global individual emissions and find corresponding limits on national aggregate emissions from this cap. All of the world's high CO
2
-emitting individuals are treated the same, regardless of where they live. Any future global emission goal (target and time frame) can be converted into national reduction targets, which are determined by “Business as Usual” projections of national carbon emissions and in-country income distributions. For example, reducing projected global emissions in 2030 by 13 GtCO
2
would require the engagement of 1.13 billion high emitters, roughly equally distributed in 4 regions: the U.S., the OECD minus the U.S., China, and the non-OECD minus China. We also modify our methodology to place a floor on emissions of the world's lowest CO
2
emitters and demonstrate that climate mitigation and alleviation of extreme poverty are largely decoupled.
Effective preexposure and postexposure prophylaxis of rabies with a highly attenuated recombinant rabies virus
Authors: Faber Milosz , Li Jianwei , Kean Rhonda B. , Hooper D. Craig , Alugupalli Kishore R. , Dietzschold Bernhard
Published: July 2009

Rabies remains an important public health problem with more than 95% of all human rabies cases caused by exposure to rabid dogs in areas where effective, inexpensive vaccines are unavailable. Because of their ability to induce strong innate and adaptive immune responses capable of clearing the infection from the CNS after a single immunization, live-attenuated rabies virus (RV) vaccines could be particularly useful not only for the global eradication of canine rabies but also for late-stage rabies postexposure prophylaxis of humans. To overcome concerns regarding the safety of live-attenuated RV vaccines, we developed the highly attenuated triple RV G variant, SPBAANGAS-GAS-GAS. In contrast to most attenuated recombinant RVs generated thus far, SPBAANGAS-GAS-GAS is completely nonpathogenic after intracranial infection of mice that are either developmentally immunocompromised (e.g., 5-day-old mice) or have inherited deficits in immune function (e.g., antibody production or type I IFN signaling), as well as normal adult animals. In addition, SPBAANGAS-GAS-GAS induces immune mechanisms capable of containing a CNS infection with pathogenic RV, thereby preventing lethal rabies encephalopathy. The lack of pathogenicity together with excellent immunogenicity and the capacity to deliver immune effectors to CNS tissues makes SPBAANGAS-GAS-GAS a promising vaccine candidate for both the preexposure and postexposure prophylaxis of rabies.
Ubiquitin degradation with its substrate, or as a monomer in a ubiquitination-independent mode, provides clues to proteasome regulation
Authors: Shabek Nitzan , Herman-Bachinsky Yifat , Ciechanover Aaron
Published: July 2009

The mechanisms that regulate the ubiquitin (Ub)-proteasome system's own components, although critically important, are largely unknown. Ub, a principal component of the system, must be maintained at adequate levels to support cellular homeostasis under basal and stressed conditions. It was suggested that Ub is degraded as part of the polyubiquitin chain along with its substrate. Here, we demonstrate in a direct manner that Ub is indeed degraded in a “piggyback” mechanism. Also, it has been shown that monomeric Ub can be rapidly degraded when a C-terminal tail of a minimal length is fused to it. The tail, which may represent the substrate or part of it, or a naturally occurring extended form of Ub, probably allows entry of the protein into the 20S catalytic chamber, while Ub serves as an anchor to the 19S complex. Here, we show that shorter-tailed Ubs, such as UBB
+1
, bind to the proteasome but because they cannot be efficiently degraded, they inhibit the degradation of other Ub system's substrates such as Myc, p21, Mdm2, and MyoD. The inhibition depends on the ability of the tailed Ubs to be ubiquitinated: their mere binding to the proteasome is not sufficient. Interestingly, the inhibition affects only substrates that must undergo ubiquitination for their degradation: ornithine decarboxylase that is targeted by the proteasome in a Ub-independent manner, is not affected by the short-tailed ubiquitinated Ubs, suggesting it binds to the 19S complex in a site different from that to which ubiquitinated substrates bind.
Community Treatment Orders and Competence to Consent
Authors: Milne Duncan , O'Brien Anthony , McKenna Brian
Published: July 2009

Objective: The aim of this paper is to explore the relationship between civil commitment under a Community Treatment Order (CTO) and competence to consent to treatment.

Method: A purposive convenience sample of 10 service users under CTOs were interviewed using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T). Ratings were compared with the ratings of 10 matched voluntary service users.

Results: Seventy percent of the CTO sample were found to be incompetent according to the MacCAT-T, compared to 20% of the comparison group ( p = 0.004). The proportion of the CTO sample found to be incompetent reduces to 50% if the subscale of appreciation is excluded ( p = 0.004). Most people in each group would elect to continue their current treatment if given the choice.

Conclusion: Findings of this study suggest that mental health law reform introducing considerations of competence could lead to a substantially different group of people being subject to CTOs. If the CTO is carefully targeted and not used excessively, it is likely to be accorded qualified acceptance for most service users for whom it is used.
Child and Family Inclusive Practice: A Pilot Program in a Community Adult Mental Health Service
Authors: Cowling Vicki , Garrett Matthew
Published: July 2009

Objective: The aim of this paper is to describe the Child and Family Inclusive Practice program (CFIP), a pilot program implemented in an adult community mental health centre in Newcastle, New South Wales, which aimed to enhance family relationships through child and family inclusive practice.

Conclusions: The CFIP used a family-focused, child-sensitive approach in which two clinicians met together with families where there was parental mental illness. Adults and children were seen together and separately. Work with parents was aimed at validating their concerns for the child, and enhancing their confidence as parents/carers. Children had the opportunity to express their concerns in a safe and protective environment and, where appropriate, were supported in their concerns if these were being put to the adult family members. The project was seen to add value to the service provision of the community mental health team, and demonstrated to clinical staff the benefits of an inclusive and whole of family approach to mental health care.
An Evaluation of Monitoring Practices in Patients on Second Generation Antipsychotics
Authors: Nguyen Dang , Brakoulias Vlasios , Boyce Philip
Published: July 2009

Objective: Treatment with second generation antipsychotics (SGAs) can increase the risk of patients with schizophrenia developing obesity, hyperlipidaemia and diabetes. Routine monitoring is recommended, but clinical practice suggests monitoring is not conducted at a rate necessary for these comorbidities. The aim was to audit what proportion of patients were having their weight, height, girth, body mass index, lipids and blood sugar levels monitored and recorded.

Method: An audit of patients with schizophrenia, discharged from three psychiatric wards, was conducted. Two data sheets were recorded for every patient and inter-rater reliability was calculated. Data were then entered into SPSS and statistical significance calculated.

Results: The sample consisted of 93 patients; SGAs were taken by 31% of admitted and 88% of discharged patients. Of these, 65% had their weight recorded, 61% height, 31% random blood sugar levels, 3% postprandial blood sugar levels, 2% glycosylated haemoglobin, and 7.5% cholesterol and triglycerides. Girth and BMI were not recorded. Abnormalities were detected in 29% of recorded BSL and 2% of recorded cholesterol.

Conclusions: Patients with schizophrenia on antipsychotics have an alarmingly low rate of monitoring of these common adverse effects and comorbidities. Clinicians need to be aware of this, so that they can improve their practice.
Children as Consumer Participants of Child and Adolescent Mental Health Services
Authors: Mitchell-Lowe Margaret , Eggleston Matthew
Published: July 2009

Objective: This pilot study explored children's perspectives of an initial assessment at outpatient child and adolescent mental health services (CAMHS).

Method: A semi-structured qualitative interview was undertaken with nine children aged 7–12 years. Transcribed interviews were analyzed to reveal common themes.

Results: Children generally coped well with the interview. They identified themes involving stigma, qualities and approaches of staff, aspects of the CAMHS environment, and anxiety about attending CAMHS as key issues.

Conclusions: This pilot study suggests that it is feasible to interview children regarding their perspectives on attending a CAMHS. Children's views of CAMHS are required to help inform developmentally appropriate service delivery.
Medical Students’ Attitudes Towards a Career in Psychiatry before and after Viewing a Promotional DVD
Authors: Robertson Tasha , Walter Garry , Soh Nerissa , Hunt Glenn , Cleary Michelle , Malhi Gin
Published: July 2009

Objectives: The objectives were, first, to determine attitudes towards psychiatry as a career among medical students currently enrolled at the University of Sydney and, second, to establish the immediate impact on those attitudes of a promotional DVD, released by the Royal Australian and New Zealand College of Psychiatrists.

Method: Medical students enrolled in the University of Sydney in 2008 were invited to complete a voluntary online questionnaire, in which their attitudes towards psychiatry were explored, and the immediate effects of a 15-minute DVD were ascertained.

Results: A total of 123 students participated. Only one student identified psychiatry as their chosen career. Medical students viewed psychiatry as the least attractive specialty for the degree to which patients are helped effectively and in terms of having a reliable scientific foundation. However, it rated well in regard to being intellectually challenging, a rapidly advancing field of medicine, and providing research opportunities and a good lifestyle. Psychiatry is less respected than most other specialties by students and they perceive this discipline to be poorly respected by other medical students and current medical practitioners. After viewing the DVD, there were improved student ratings of the benefits of a career in psychiatry, especially in relation to the specialty being enjoyable, offering effective treatment and having a scientific foundation. There was also enhanced understanding of the role of a psychiatrist in just over half of the participants and increased interest in psychiatry in about 30% of participants. The DVD was most effective in increasing awareness of the diversity of subspecialties available within psychiatry, good lifestyle factors, and the training involved.

Conclusion: Among medical students, psychiatry is perceived as unattractive and fails to command the respect afforded other specialties. The viewing of a promotional DVD by medical students was found to be effective in improving their attitudes towards psychiatry and increasing their interest in pursuing a career in the specialty. However, the long-term impact of this modest improvement is unknown and the low survey response rate limits the extent to which the results can be generalized.
The University of Western Australia Institute of Psychiatry for Medical Students: An Australian First
Authors: Lyons Zaza , Power Brian , Bilyk Natalia , Claassen Johann
Published: July 2009

Objective: Recruitment of medical graduates into psychiatry has become a growing issue over the last few decades. This paper describes the implementation of an innovative program, based on a Canadian concept, that aimed to promote psychiatry as a career choice to medical students, to immerse them in the ‘world of psychiatry’, and introduce them to potential mentors. The University of Western Australia Institute of Psychiatry for Medical Students was a week-long program that provided medical students with an opportunity to participate in a diverse agenda of interactive seminars on a range of psychiatric subspecialties and the neurosciences. Students were also able to attend elective sessions and meet registrars and psychiatrists on an informal basis. Lunches and social events were also provided.

Conclusion: Twenty-one students attended the inaugural Institute. Twenty-seven speakers contributed to the morning seminars and there were 17 clinical elective site visits. Feedback from students was positive and the week was rated highly, both in terms of its organization and from an academic perspective. It is planned to run the Institute annually and, in time, it is hoped that it will increase the numbers of students who choose psychiatry as a career option.
Alprazolam Prescribing in Tasmania: A Two-Fold Intervention Designed to Reduce Inappropriate Prescribing and Concomitant Opiate Prescription
Authors: Hooper Stuart , Bruno Raimondo , Sharpe Mary , Tahmindjis Alex
Published: July 2009

Objective: The population rate of alprazolam prescribing in Tasmania has been more than double that of national rates. Serious adverse events have been observed through co-administration of opioid medications with alprazolam. A two-fold intervention, comprising GP education coupled with changes to prescribing regulations, was designed with the intention to decrease inappropriate prescribing of alprazolam and thereby reduce adverse outcomes. The aim of this study was to assess the impact of the intervention on prescribing rates.

Method: We measured the number of alprazolam prescriptions for the years prior to and the year following the intervention. Health Insurance Commission data were utilized to enable comparison of subsidized prescription rates for alprazolam in Tasmania, and compared with national data. Participants were registered medical practitioners in Tasmania who were potential prescribers of alprazolam. The interventions were three GP Education Meetings during June 2007, one in each of the major regions of Tasmania, regarding evidence-based interventions for panic disorder. Changes to regulatory procedures to minimize co-prescription of alprazolam with opioids was implemented in September 2007.

Results: A reduction in alprazolam prescribing in Tasmania occurred after the interventions.

Conclusion: Education can be an effective strategy to influence prescribing behaviour of doctors. It is likely that this effect can be augmented by adoption of more stringent regulatory requirements.
The Cost of Relapse in Schizophrenia and Schizoaffective Disorder
Authors: Fitzgerald Paul , de Castella Anthony , Arya Dinesh , Simons W. Robert , Eggleston Andrew , Meere Sharon , Kulkarni Jayashari
Published: July 2009

Objective: The aim of this study was to quantify the costs and resource utilization associated with a relapse of schizophrenia or schizoaffective disorder.

Methods: The study comprised a retrospective audit of data from 200 patients diagnosed with schizophrenia or schizoaffective disorder who were admitted to hospital for a relapse of their disorder in two mental health services in Australia between 1 June 2001 and 31 May 2002. Resource use and costing data were collected for 12 months before and 12 months after the hospitalization.

Results: There was an increase in contacts per month and associated outpatient costs after the index admission which persisted for the full 12 month data collection period (total of AUD $637). There was also a total increase in hospital costs but this did not persist beyond the first 2 months of the follow-up period and is likely explained by the index admission.

Conclusions: Increased healthcare resource utilization and costs results from relapse in patients with schizophrenia or schizoaffective disorder. An increase in service use and costs persist for a considerable time period after an episode of relapse.
Quantitative proteomics identifies a Dab2/integrin module regulating cell migration
Authors: Teckchandani Anjali , Toida Natalie , Goodchild Jake , Henderson Christine , Watts Julian , Wollscheid Bernd , Cooper Jonathan A.
Published: July 2009

Clathrin-associated endocytic adapters recruit cargoes to coated pits as a first step in endocytosis. We developed an unbiased quantitative proteomics approach to identify and quantify glycoprotein cargoes for an endocytic adapter, Dab2. Surface levels of integrins β1, α1, α2, and α3 but not α5 or αv chains were specifically increased on Dab2-deficient HeLa cells. Dab2 colocalizes with integrin β1 in coated pits that are dispersed over the cell surface, suggesting that it regulates bulk endocytosis of inactive integrins. Depletion of Dab2 inhibits cell migration and polarized movement of integrin β1 and vinculin to the leading edge. By manipulating intracellular and surface integrin β1 levels, we show that migration speed correlates with the intracellular integrin pool but not the surface level. Together, these results suggest that Dab2 internalizes integrins freely diffusing on the cell surface and that Dab2 regulates migration, perhaps by maintaining an internal pool of integrins that can be recycled to create new adhesions at the leading edge.
Organelle tethering by a homotypic PDZ interaction underlies formation of the Golgi membrane network
Authors: Sengupta Debrup , Truschel Steven , Bachert Collin , Linstedt Adam D.
Published: July 2009

Formation of the ribbon-like membrane network of the Golgi apparatus depends on GM130 and GRASP65, but the mechanism is unknown. We developed an in vivo organelle tethering assaying in which GRASP65 was targeted to the mitochondrial outer membrane either directly or via binding to GM130. Mitochondria bearing GRASP65 became tethered to one another, and this depended on a GRASP65 PDZ domain that was also required for GRASP65 self-interaction. Point mutation within the predicted binding groove of the GRASP65 PDZ domain blocked both tethering and, in a gene replacement assay, Golgi ribbon formation. Tethering also required proximate membrane anchoring of the PDZ domain, suggesting a mechanism that orientates the PDZ binding groove to favor interactions in trans. Thus, a homotypic PDZ interaction mediates organelle tethering in living cells.
Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti–CTLA-4 antibodies
Authors: Peggs Karl S. , Quezada Sergio A. , Chambers Cynthia A. , Korman Alan J. , Allison James P.
Published: July 2009

Cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) is a critical negative regulator of immune responses. Uniquely among known inhibitory receptors, its genetic ablation results in a fulminating and fatal lymphoproliferative disorder. This central regulatory role led to the development of antibodies designed to block CTLA-4 activity in vivo, aiming to enhance immune responses against cancer. Despite their preclinical efficacy and promising clinical activity against late stage metastatic melanoma, the critical cellular targets for their activity remains unclear. In particular, debate has focused on whether the effector T cell (Teff) or regulatory T cell (T reg cell) compartment is the primary target of antibody-mediated blockade. We developed a mouse expressing human instead of mouse CTLA-4, allowing us to evaluate the independent contributions of CTLA-4 blockade of each T cell compartment during cancer immunotherapy in an in vivo model of mouse melanoma. The data show that although blockade on effector cells significantly improves tumor protection, unicompartmental blockade on regulatory cells completely fails to enhance antitumor responses. However, concomitant blockade of both compartments leads to a synergistic effect and maximal antitumor activity. We conclude that the combination of direct enhancement of Teff cell function and concomitant inhibition of T reg cell activity through blockade of CTLA-4 on both cell types is essential for mediating the full therapeutic effects of anti–CTLA-4 antibodies during cancer immunotherapy.
Molecular Characterization ofStenotrophomonas maltophiliaIsolates from Cystic Fibrosis Patients and the Hospital Environment
Authors: Marzuillo Carolina , Giusti Maria De , Tufi Daniela , Giordano Alessandra , Cimmuto Angela Del , Quattrucci Serena , Mancini Carlo , Villari Paolo
Published: July 2009

Objectives.

To ascertain whether cystic fibrosis (CF) patients are colonized or infected with unique or multiple strains ofStenotrophomonas maltophilia; to understand whether some strains colonize or infect more than 1 patient, indicating clonal spread; and to explore the molecular heterogeneity of hospital water isolates and their correlation with clinical isolates.

Setting.

The regional CF center of Policlinico “Umberto I” of Rome, Italy.

Methods.

The study was carried out on a random sample ofS. maltophiliaisolates (n= 110) collected from CF patients (n= 50) during the period 2002–2005 and on 24 water isolates obtained during a monitoring program in the first 6 months of 2005. Home environmental samplings were not performed. All isolates, which were recovered from cultures of specimens obtained in both inpatient and outpatient settings, were genotyped with DNA macrorestriction analysis with the restriction enzymeXbaland pulsed-field gel electrophoresis.

Results.

One-third of the patients with repeated episodes ofS. maltophiliainfection or colonization hosted more than 1 strain. A potential transmission, defined as the isolation of the same strain in 2 or more patients, occurred 5 times, showing a frequency of potential transmission episodes slightly higher than previously reported. Water, taps, and sinks of the different rooms of the CF center tended to be persistently colonized with the same strain ofS. maltophilia, with no correlation between clinical and water-associated isolates.

Conclusions.

The study does not provide sufficient data to conclude definitively that isolation of colonized or infected CF patients and control of hospital water systems contamination would be beneficial infection control measures. Epidemiologic analytical studies that correlate the presence ofS. maltophiliawith clinical outcomes are strongly needed.
Observations of spontaneous toroidal flow in the LHD
Authors: Yoshinuma M. , Ida K. , Yokoyama M. , Nagaoka K. , Osakabe M.
Published: July 2009

Spontaneous toroidal flows driven by radial electric fields and ion temperature gradients are studied in the Large Helical Device (LHD). The positive radial electric field drives spontaneous flow in the counter-direction at the plasma edge and in the co-direction near the magnetic axis. The difference in the direction of the spontaneous flow between the core and the edge is considered to be due to the difference in the ratio of the helical ripple to the toroidal ripple. It is clearly observed that the ion temperature gradient causes a spontaneous toroidal flow and is expected to be one of the dominant components of the toroidal flows in the high ion temperature discharges in the LHD.
Transcriptional and post-transcriptional profile of human chromosome 21
Authors: Nikolaev Sergey I. , Deutsch Samuel , Genolet Raphael , Borel Christelle , Parand Leila , Ucla Catherine , Schütz Frederic , Duriaux Sail Genevieve , Dupré Yann , Jaquier-Gubler Pascale , Araud Tanguy , Conne Beatrice , Descombes Patrick , Vassalli Jean-Dominique , Curran Joseph , Antonarakis Stylianos E.
Published: July 2009

Recent studies have demonstrated extensive transcriptional activity across the human genome, a substantial fraction of which is not associated with any functional annotation. However, very little is known regarding the post-transcriptional processes that operate within the different classes of RNA molecules. To characterize the post-transcriptional properties of expressed sequences from human chromosome 21 (HSA21), we separated RNA molecules from three cell lines (GM06990, HeLa S3, and SK-N-AS) according to their ribosome content by sucrose gradient fractionation. Polyribosomal-associated RNA and total RNA were subsequently hybridized to genomic tiling arrays. We found that ∼50% of the transcriptional signals were located outside of annotated exons and were considered as TARs (transcriptionally active regions). Although TARs were observed among polysome-associated RNAs, RT-PCR and RACE experiments revealed that ∼40% were likely to represent nonspecific cross-hybridization artifacts. Bioinformatics discrimination of TARs according to conservation and sequence complexity allowed us to identify a set of high-confidence TARs. This set of TARs was significantly depleted in the polysomes, suggesting that it was not likely to be involved in translation. Analysis of polysome representation of RefSeq exons showed that at least 15% of RefSeq transcripts undergo significant post-transcriptional regulation in at least two of the three cell lines tested. Among the regulated transcripts, enrichment analysis revealed an over-representation of genes involved in Alzheimer's disease (AD), including APP and the BACE1 protease that cleaves APP to produce the pathogenic beta 42 peptide. We demonstrate that the combination of RNA fractionation and tiling arrays is a powerful method to assess the transcriptional and post-transcriptional properties of genomic regions.
Long‐term outcome of non‐fistulizing (ulcers, stricture) perianal Crohn’s disease in patients treated with infliximab
Authors: BOUGUEN G. , TROUILLOUD I. , SIPROUDHIS L. , OUSSALAH A. , BIGARD M.‐A. , BRETAGNE J.‐F. , PEYRIN‐BIROULET L.
Published: July 2009

Background  In Crohn’s disease, anal ulcers and stricture can be disabling.

Aim  To evaluate long‐term outcome of non‐fistulizing perianal Crohn’s disease under infliximab.

Methods  The medical records of 99 patients with non‐fistulizing perianal Crohn’s disease at first infliximab infusion were reviewed. Complete responses (ulcer healing or stricture regression) after induction infliximab therapy and at the maximal follow‐up were assessed.

Results  Ninety‐four patients (94.9%) had ulcers, 22 (22.2%) had stricture and 31 (31.3%) had draining perianal fistulas at first infliximab infusion. After infliximab induction therapy, 40/94 (42.5%) patients with ulcers, 4/22 (18.2%) with stricture and 10/31 (32.2%) with fistulas had a complete response. Eight patients were lost to follow‐up. After a median follow‐up of 175 weeks (range, 13–459), complete response rates for ulcers, stricture and fistulas were 72.3% (68/94), 54.5% (12/22) and 54.8% (20/31) respectively. Long‐term response for cavitating ulcer was positively associated with concomitant immunosuppressant use (P = 0.017) and older age (P = 0.049). Among the 12 patients with complete regression of stricture, 6 patients also had anal dilatation. Complete response was associated with perianal pain relief and disappearance of soiling. Three patients with ulcers developed an anal abscess.

Conclusions  Infliximab therapy may be effective in inducing and maintaining response for ulcers.
Prescription rates of protective co‐therapy for NSAID users at high GI risk and results of attempts to improve adherence to guidelines
Authors: LAINE L. , CONNORS L. , GRIFFIN M. R. , CURTIS S. P. , KAUR A. , CANNON C. P.
Published: July 2009

Background  Protective co‐therapy is recommended in NSAID users with GI risk factors, but adherence is poor.

Aim  To assess the proportion of NSAID users receiving co‐therapy and strategies to improve adherence.

Methods  Arthritis patients ≥50 years of age received etoricoxib or diclofenac in a double‐blind randomized trial. Reminders that high‐risk patients (age ≥ 65; previous ulcer/haemorrhage; corticosteroid, anticoagulant, aspirin use) should receive co‐therapy were given at study initiation. Free PPI was provided. An intervention midway through the study included a written reminder and required written response regarding co‐therapy.

Results  16 244/23 504 (69%) patients had GI risk factors. Pre‐intervention, co‐therapy was most common with previous ulcer/haemorrhage [706/1107 (64%)] and 3–4 risk factors [331/519 (64%)]. In the 10 026 patients enrolled pre‐intervention and remaining in the study ≥6 months after, co‐therapy in high‐risk patients increased from 2958/6843 (43%) to 4177/6843 (61%) (difference = 18%; 95% CI 16%,19%). The increase was greater outside the US (22%; 19%,24%) than in the US (15%; 13%,17%).

Conclusions  Less than 50% of NSAID users with GI risk factors are given protective co‐therapy – even if prescribers are given reminders and cost is not an issue. Direct communication requiring written response significantly increased adherence to guidelines, but achieving higher levels of adherence will require additional strategies.
Utility of diagnostic tests in the follow‐up of egg‐allergic children
Authors: Diéguez Ma C. , Cerecedo I. , Muriel A. , Zamora J. , Abraira V. , Camacho E. , Antón M. , De La Hoz B.
Published: July 2009

Background
Better knowledge of the accuracy of a skin prick test (SPT) and specific IgE (sIgE) levels to egg allergens would help to identify persistent egg‐allergic children, avoiding unnecessary risky challenges. This study was designed to assess the accuracy of a SPT and sIgE levels to egg allergens in order to determine persistent egg allergy in IgE‐mediated allergic children after an egg‐free diet.

Methods
Children below 16 years were prospectively and consecutively recruited. Inclusion criteria were: allergy to egg proteins (children with a positive clinical case of IgE‐mediated egg allergy and a positive SPT to egg allergens and/or positive sIgE levels), and strict egg avoidance diet followed for at least 6 months. Clinical histories were recorded and all patients underwent SPTs, sIgE levels to egg allergens and the gold standard ‐a double‐blind placebo‐controlled egg challenge (DBPCFG). DBPCFG was interpreted without knowledge of the results of the other tests and vice‐versa. A SPT and sIgE levels' ROC curves analysis was performed to compare the diagnostic performance of the different tests.

Results
Finally, 157 children were included in the study. One hundred out of these 157 children (63.7%) had a positive oral challenge. Ninety‐six were male (61%), and the median age was 2.5 years. One hundred and three (66.9%) had atopic dermatitis. A 7 mm egg white prick test had a positive likelihood ratio (+LR) of 6.7, and a level of 1.3 KU/L egg white‐sIgE had a +LR of 5.1. A 7 mm egg white SPT had a positive predictive value of 92.3% (95% CI 85.1–99.5), and for a 9 mm egg white SPT this value was 95.6% (95% CI 87.3–100.0). For egg white‐sIgE, 1.5 KU/L had a positive predictive value of 90.4% (95% CI 82.4–98.4) and for 25 KU/L it was 100.0% (95% CI 100.0–100.0). SPTs with ovotransferrin and lysozyme showed the lowest accuracy, followed by yolk and ovalbumin SPTs.

Conclusion
This study is the first to evaluate both tests (SPT and sIgE levels) and all egg allergens to determine the persistence of egg allergy in IgE‐mediated allergic children. Measuring the SPT and sIgE levels is useful to predict persistent allergy in these children, especially with the egg white complete extract. An oral challenge should not be performed in egg allergic paediatric patients with either an egg white prick test above 7 mm or a white egg‐sIgE determination above 1.3 KU/L, because there is a 90% probability of remaining allergic.
An abnormal screening glucose challenge test in pregnancy predicts postpartum metabolic dysfunction, even when the antepartum oral glucose tolerance test is normal
Authors: Retnakaran Ravi , Qi Ying , Sermer Mathew , Connelly Philip W. , Hanley Anthony J. G. , Zinman Bernard
Published: July 2009

Objective  In pregnancy, a normal result on the oral glucose tolerance test (OGTT) that follows an abnormal screening glucose challenge test (GCT) is considered a reassuring finding, requiring no further intervention. The obstetrical and metabolic implications of this presentation, however, have not been well studied. Thus, we sought to characterize the obstetrical and postpartum metabolic significance of an abnormal GCT in women with normal glucose tolerance (NGT) on antepartum OGTT.

Design/patients/measurements  A total of 259 women with NGT on antepartum OGTT (166 with an abnormal GCT and 93 with a normal GCT) underwent (i) metabolic evaluation in pregnancy, (ii) assessment of obstetrical outcome at delivery and (iii) repeat metabolic characterization by OGTT at 3 months postpartum.

Results  Neither infant birthweight nor Caesarean section rate differed between the abnormal GCT and normal GCT groups. At 3 months postpartum, however, compared to the normal GCT group, the abnormal GCT group exhibited greater glycaemia (mean area under the glucose curve (AUCgluc) 19·6 vs. 18·3, P = 0·0021), lower insulin sensitivity (median insulin sensitivity index (ISOGTT) 9·5 vs. 11·3, P = 0·0243) and poorer beta‐cell function (median insulinogenic index/Homeostasis Model Assessment of Insulin Resistance (HOMA‐IR) 9·8 vs. 14·1, P = 0·0013). On multiple linear regression analyses, an abnormal GCT emerged as (i) the strongest independent predictor of postpartum AUCgluc (t = 2·77, P = 0·006) and (ii) the strongest independent negative predictor of log insulinogenic index/HOMA‐IR (t = –2·36, P = 0·0191). Furthermore, the GCT was the antepartum parameter that best predicted postpartum pre‐diabetes (area under the receiver operating characteristic curve (AROC) = 0·754).

Conclusions  An abnormal antepartum GCT, even when followed by a normal OGTT, is associated with postpartum glycaemia and beta‐cell dysfunction, factors that may portend an increased future risk of diabetes in this patient population.
Do leaves of plants on phosphorus‐impoverished soils contain high concentrations of phenolic defence compounds?
Authors: Wright David M. , Jordan Greg J. , Lee William G. , Duncan Richard P. , Forsyth David M. , Coomes David A.
Published: July 2009

1. Prominent theories of plant defence have predicted that plants growing on nutrient‐poor soils produce more phenolic defence compounds than those on richer soils. Only recently has the Protein Competition Model (PCM) of phenolic allocation suggested that N and P limitation could have different effects because the nutrients are involved in different cellular metabolic processes.

2. We extend the prediction of the PCM and hypothesize that N will have a greater influence on the production of phenolic defensive compounds than P availability, because N limitation reduces protein production and thus competition for phenylalanine, a precursor of many phenolic compounds. In contrast, P acts as a recyclable cofactor in these reactions, allowing protein and hence phenolic production to continue under low P conditions.

3. We test this hypothesis by comparing the foliar concentrations of phenolic compounds in (i) phenotypes of 21 species growing on P‐rich alluvial terraces and P‐depleted marine terraces in southern New Zealand, and (ii) 87 species growing under similar climates on comparatively P‐rich soils in New Zealand vs. P‐depleted soils in Tasmania.

4. Foliar P concentrations of plants from the marine terraces were about half those of plants from alluvial soils, and much lower in Tasmania than in New Zealand. However, foliar concentrations of N and phenolic compounds were similar across sites in both comparisons, supporting the hypothesis that N availability is a more important determinant of plant investment in phenolic defensive compounds than P availability. We found no indication that reduced soil P levels influenced plant concentrations of phenolic compounds. There was wide variation in the foliar N and P concentrations among species, and those with low foliar nutrient concentrations produced more phenolics (including condensed tannins).

5. Our study is the first trait comparison extending beyond standard leaf economics to include secondary metabolites related to defence in forest plants, and emphasizes that N and P have different influences on the production of phenolic defence compounds.
Carbon accumulation at depth in Ferralsols under zero‐till subtropical agriculture
Authors: BODDEY ROBERT M. , JANTALIA CLAUDIA P. , CONCEIÇÃO PAULO C. , ZANATTA JOSILEIA A. , BAYER CIMÉLIO , MIELNICZUK JOÃO , DIECKOW JEFERSON , DOS SANTOS HENRIQUE P. , DENARDIN JOSÉ E. , AITA CELSO , GIACOMINI SANDRO J. , ALVES BRUNO J.R. , URQUIAGA SEGUNDO
Published: July 2009

Conservation agriculture can provide a low‐cost competitive option to mitigate global warming with reduction or elimination of soil tillage and increase soil organic carbon (SOC). Most studies have evaluated the impact of zero till (ZT) only on surface soil layers (down to 30 cm), and few studies have been performed on the potential for C accumulation in deeper layers (0–100 cm) of tropical and subtropical soils. In order to determine whether the change from conventional tillage (CT) to ZT has induced a net gain in SOC, three long‐term experiments (15–26 years) on free‐draining Ferralsols in the subtropical region of South Brazil were sampled and the SOC stocks to 30 and 100 cm calculated on an equivalent soil mass basis. In rotations containing intercropped or cover‐crop legumes, there were significant accumulations of SOC in ZT soils varying from 5 to 8 Mg ha−1 in comparison with CT management, equivalent to annual soil C accumulation rates of between 0.04 and 0.88 Mg ha−1. However, the potential for soil C accumulation was considerably increased (varying from 0.48 to 1.53 Mg ha−1 yr−1) when considering the soil profile down to 100 cm depth. On average the estimate of soil C accumulation to 100 cm depth was 59% greater than that for soil C accumulated to 30 cm. These findings suggest that increasing sampling depth from 30 cm (as presently recommended by the IPCC) to 100 cm, may increase substantially the estimates of potential CO2 mitigation induced by the change from CT to ZT on the free‐draining Ferralsols of the tropics and subtropics. It was evident that that legumes which contributed a net input of biologically fixed N played an important role in promoting soil C accumulation in these soils under ZT, perhaps due to a slow‐release of N from decaying surface residues/roots which favored maize root growth.
Predicted impact of climate change on European bats in relation to their biogeographic patterns
Authors: REBELO HUGO , TARROSO PEDRO , JONES GARETH
Published: July 2009

There has been considerable recent interest concerning the impact of climate change on a wide range of taxa. However, little is known about how the biogeographic affinities of taxa may affect their responses to these impacts. Our main aim was to study how predicted climate change will affect the distribution of 28 European bat species grouped by their biogeographic patterns as determined by a spatial Principal Component Analysis. Using presence‐only modelling techniques and climatic data (minimum temperature, average temperature, precipitation, humidity and daily temperature range) for four different climate change scenarios (IPCC scenarios ranging from the most extreme A1FI, A2, B2 to the least severe, B1), we predict the potential geographic distribution of bat species in Europe grouped according to their biogeographic patterns for the years 2020–2030, 2050–2060 and 2090–2100. Biogeographic patterns exert a great influence on a species' response to climate change. Bat species more associated with colder climates, hence northern latitudes, could be more severely affected with some extinctions predicted by the end of the century. The Mediterranean and Temperate groups seem to be more tolerant of temperature increases, however, their projections varied considerably under different climate change scenarios. Scenario A1FI was clearly the most detrimental for European bat diversity, with several extinctions and declines in occupied area predicted for several species. The B scenarios were less damaging and even predicted that some species could increase their geographical ranges. However, all models only took into account climatic envelopes whereas available habitat and species interactions will also probably play an important role in delimiting future distribution patterns. The models may therefore generate ‘best case’ predictions about future changes in the distribution of European bats.
Two‐step vegetation response to enhanced precipitation in Northeast Brazil during Heinrich event 1
Authors: DUPONT LYDIE M. , SCHLÜTZ FRANK , EWAH CAROL TEBOH , JENNERJAHN TIM C. , PAUL ANDRÉ , BEHLING HERMANN
Published: July 2009

High resolution palynological and geochemical data of sediment core GeoB 3910‐2 (located offshore Northeast Brazil) spanning the period between 19 600 and 14 500 calibrated year bp (19.6–14.5 ka) show a land‐cover change in the catchment area of local rivers in two steps related to changes in precipitation associated with Heinrich Event 1 (H1 stadial). At the end of the last glacial maximum, the landscape in semi‐arid Northeast Brazil was dominated by a very dry type of caatinga vegetation, mainly composed of grasslands with some herbs and shrubs. After 18 ka, considerably more humid conditions are suggested by changes in the vegetation and by Corg and C/N data indicative of fluvial erosion. The caatinga became wetter and along lakes and rivers, sedges and gallery forest expanded. The most humid period was recorded between 16.5 and 15 ka, when humid gallery (and floodplain) forest and even small patches of mountainous Atlantic rain forest occurred together with dry forest, the latter being considered as a rather lush type of caatinga vegetation. During this humid phase erosion decreased as less lithogenic material and more organic terrestrial material were deposited on the continental slope of northern Brazil. After 15 ka arid conditions returned. During the humid second phase of the H1 stadial, a rich variety of landscapes existed in Northeast Brazil and during the drier periods small pockets of forest could probably survive in favorable spots, which would have increased the resilience of the forest to climate change.
The lectin Jacalin induces human B‐lymphocyte apoptosis through glycosylation‐dependent interaction with CD45
Authors: Ma Bruce Yong , Yoshida Kaori , Baba Makoto , Nonaka Motohiro , Matsumoto Shogo , Kawasaki Nobuko , Asano Shinji , Kawasaki Toshisuke
Published: July 2009

It has been well established that CD45 is a key receptor‐type protein tyrosine phosphatase (PTPase) regulating Src‐family protein tyrosine kinase (Src‐PTK) in T and B lymphocytes. However, precisely how CD45 exerts its effect in these lymphocytes remains controversial. We recently reported that Jacalin, an α‐O‐glycoside of the disaccharide Thomsen–Friedenreich antigen‐specific lectin from jackfruit seeds, caused marked T‐cell activation in response to T‐cell receptor ligation and CD28 costimulation by binding to CD45. On extending the reported research, we found that CD45 and isoforms are major Jacalin receptors on B lymphocytes, and that the glycosylation of CD45 is involved in the interaction of Jacalin with the PTPase. In contrast to Jacalin‐stimulated T‐cell activation, we found that Jacalin induced human B‐lymphocyte apoptosis, resulting in calcium mobilization and calpain activation, suggesting that the calcium–calpain pathway may mediate the Jacalin‐induced apoptosis. Importantly, the apoptosis was effectively blocked by a specific CD45 PTPase inhibitor, indicating that Jacalin induces human B‐lymphocyte apoptosis through CD45 triggering. Furthermore, we found that Jacalin significantly increased the C‐terminal inhibitory tyrosine (Tyr507) phosphorylation of Src‐PTK Lyn, one of the major substrates of CD45 PTPase, and this effect was also observed on incubation of B lymphocytes with the specific CD45 PTPase inhibitor, suggesting that Jacalin stimulation results in increasing C‐terminal tyrosine phosphorylation of the kinase through inhibition of CD45 tyrosine phosphatase activity in human B lymphocytes. Therefore, the down‐modulation of Lyn kinase may play a role in the regulation of B‐lymphocyte viability.