bluuebunny/crossref_metadata_2025 huggingface dataset:
Disease progression model in subjects with mild cognitive impairment from the Alzheimer's disease neuroimaging initiative: CSF biomarkers predict population subtypes
Authors: Samtani Mahesh N. , Raghavan Nandini , Shi Yingqi , Novak Gerald , Farnum Michael , Lobanov Victor , Schultz Tim , Yang Eric , DiBernardo Allitia , Narayan Vaibhav A. ,   the Alzheimer' s Disease Neuroimaging Initiative
Published: April 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Amnestic mild cognitive impairment MCI) represents the prodromal stage of Alzheimer's dementia and this disease progresses in a non‐linear fashion.

• Disease progression depends on a variety of demographic, biochemical, genetic and cognitive factors.

WHAT THIS STUDY ADDS

• Baseline CSF biomarkers carry information about disease pathology and critical thresholds for these markers (Aβ and p‐tau181P) have been identified that allow segregation of the population into MCI progressers and non‐progressers.

AIM The objective is to develop a semi‐mechanistic disease progression model for mild cognitive impairment (MCI) subjects. The model aims to describe the longitudinal progression of ADAS‐cog scores from the Alzheimer's disease neuroimaging initiative trial that had data from 198 MCI subjects with cerebrospinal fluid (CSF) information who were followed for 3 years.

METHOD Various covariates were tested on disease progression parameters and these variables fell into six categories: imaging volumetrics, biochemical, genetic, demographic, cognitive tests and CSF biomarkers.

RESULTS CSF biomarkers were associated with both baseline disease score and disease progression rate in subjects with MCI. Baseline disease score was also correlated with atrophy measured using hippocampal volume. Progression rate was also predicted by executive functioning as measured by the Trail B‐test.

CONCLUSION CSF biomarkers have the ability to discriminate MCI subjects into sub‐populations that exhibit markedly different rates of disease progression on the ADAS‐cog scale. These biomarkers can therefore be utilized for designing clinical trials enriched with subjects that carry the underlying disease pathology.
Sex differences in cardiovascular drug‐induced adverse reactions causing hospital admissions
Authors: Rodenburg Eline M. , Stricker Bruno H. , Visser Loes E.
Published: April 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Cardiovascular disease, disease outcome, drug treatment and drug response differ between men and women.

WHAT THIS STUDY ADDS

• Adverse drug reactions attributed to cardiovascular drugs that require hospital admission show differences between men and women, even after taking into account age and the total number of drug prescriptions.

AIMS Cardiovascular disease in women is often underestimated. The effects of cardiovascular drugs differ between the sexes because of pharmacokinetic and pharmacodynamic differences. Adverse drug reactions (ADRs) within these drug classes may have serious consequences, leading to hospital admission. We aimed to study differences between men and women in hospital admissions for ADRs due to cardiovascular drugs.

METHODS We conducted a nationwide study of all hospital admissions between 2000 and 2005 with data from the Dutch National Medical Register. Relative risks were calculated of hospital admissions due to ADRs to the different cardiovascular drug groups for women compared with men. By an ecological design, risks were adjusted for the total number of Dutch inhabitants and the total number of prescriptions.

RESULTS In total, 14 207 of the hospital admissions (34% of all ADR‐related admissions) were attributed to cardiovascular drugs [7690 in women (54%; 95% confidence interval 53–55%)]. ‘Anticoagulants and salicylates’ (n= 8988), ‘high‐ and low‐ceiling diuretics’ (n= 2242) and ‘cardiotonic glycosides’ (n= 932) were responsible for the majority of the ADR‐related hospital admissions. The most pronounced sex differences were seen in users of low‐ceiling diuretics (relative risk 4.02; 95% confidence interval 3.12–5.19), cardiotonic glycosides (relative risk 2.38; 95% confidence interval 2.06–2.74), high‐ceiling diuretics (relative risk 2.10; 95% confidence interval 1.91–2.32) and coronary vasodilators (relative risk 0.77; 95% confidence interval 0.65–0.91).

CONCLUSIONS Clear sex differences exist in ADRs requiring hospital admission for different cardiovascular drug groups. Sex differences should be taken into account in the prescription and evaluation of drugs.
Regional differences in symptomatic fever management among paediatricians in Switzerland: the results of a cross‐sectional Web‐based survey
Authors: Lava Sebastiano A. G. , Simonetti Giacomo D. , Ferrarini Alessandra , Ramelli Gian Paolo , Bianchetti Mario G.
Published: April 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• In children antipyretic drugs should be prescribed to treat the general discomfort that accompanies fever. Nonetheless, a gap often exists between available evidence and clinical practice.

• Fever is often a cause of fear among both parents and health care providers.

• Prescription patterns of several drugs are modulated by socio‐cultural factors.

WHAT THIS STUDY ADDS

• Among the main regions of Switzerland there are significant regional differences in symptomatic fever management as well as in the perceived frequency of fear of fever.

• Paediatricians active in the German speaking region less frequently differ from available recommendations than their colleagues active in the French and Italian speaking regions.

AIMS In symptomatic fever management, there is often a gap between everyday clinical practice and current evidence. We were interested to see whether the three linguistic regions of Switzerland differ in the management of fever.

METHODS A close‐ended questionnaire, sent to 900 Swiss paediatricians, was answered by 322 paediatricians. Two hundred and fourteen respondents were active in the German speaking, 78 in the French speaking and 30 in the Italian speaking region.

RESULTS Paediatricians from the French and Italian speaking regions identify a lower temperature threshold for initiating a treatment and more frequently reduce it for children with a history of febrile seizures. A reduced general appearance leads more frequently to a lower threshold for treatment in the German speaking than in the French and Italian speaking areas. Among 1.5 and 5‐year‐old children the preference for the rectal route is more pronounced in the German than in the French speaking region. French speaking respondents more frequently prescribe ibuprofen and an alternating regimen with two drugs than German speaking respondents. Finally, the stated occurrence of exaggerated fear of fever was higher in the German and Italian speaking regions.

CONCLUSIONS Switzerland offers the opportunity to compare three different regions with respect to management of febrile children. This inquiry shows regional differences in symptomatic fever management and in the perceived frequency of exaggerated fear of fever. The gap between available evidence and clinical practice is more pronounced in the French and in the Italian speaking regions than in the German speaking region.
A novel immunogenic CS1‐specific peptide inducing antigen‐specific cytotoxic T lymphocytes targeting multiple myeloma
Authors: Bae Jooeun , Song Weihua , Smith Robert , Daley John , Tai Yu‐Tzu , Anderson Kenneth C. , Munshi Nikhil C.
Published: April 2012

The CS1 antigen provides a unique target for the development of an immunotherapeutic strategy to treat patients with multiple myeloma (MM). This study aimed to identify HLA‐A2+ immunogenic peptides from the CS1 antigen, which induce peptide‐specific cytotoxic T lymphocytes (CTL) against HLA‐A2+ MM cells. We identified a novel immunogenic HLA‐A2‐specific CS1239‐247 (SLFVLGLFL) peptide, which induced CS1‐specific CTL (CS1‐CTL) to MM cells. The CS1‐CTL showed a distinct phenotype, with an increased percentage of effector memory and activated CTL and a decreased percentage of naïve CTL. CS1239‐247 peptide‐specific CD8+ T cells were detected by DimerX analyses and demonstrated functional activities specific to the peptide. The CTL displayed HLA‐A2‐restricted and antigen‐specific cytotoxicity, proliferation, degranulation and γ‐interferon (IFN‐γ) production against both primary MM cells and MM cell lines. In addition, the effector memory cells subset (CD45RO+CCR7−/CD3+CD8+) within CS1‐CTL showed a higher level of CD107a degranulation and IFN‐γ production as compared to effector cells (CD45RO−CCR7−/CD3+CD8+) against HLA‐A2+ primary MM cells or MM cell lines. In conclusion, this study introduced a novel immunogenic HLA‐A2‐specific CS1239‐247 peptide capable of inducing antigen‐specific CTL against MM cells that will provide a framework for its application as a novel MM immunotherapy.
Inhibitor incidence after intensive FVIII replacement for surgery in mild and moderate haemophilia A: a prospective national study in the Netherlands
Authors: Eckhardt Corien L. , Mauser‐Bunschoten Evelien P. , Peters Marjolein , Leebeek Frank W. G. , van der Meer Felix J. M. , Fijnvandraat Karin
Published: April 2012

Inhibitor development is currently the most severe complication in mild/moderate haemophilia A patients, causing increased bleeding tendency, hospitalization and mortality. It has been suggested that receiving high doses of factor VIII (FVIII) concentrates for surgical procedures is an important risk factor for inhibitor development in these patients. The current multicentre study aimed to determine prospectively the incidence of inhibitor development after intensive FVIII replacement therapy for surgical procedures in patients with mild/moderate haemophilia A. All consecutive patients with mild/moderate haemophilia A were included when they required at least 10 000 iu of FVIII concentrates (or 250 iu/kg) for 5 or more days for a surgical procedure. Potential clinical risk factors for inhibitor development and results of inhibitor tests were collected. Forty‐six patients with a median age of 54 years (interquartile range, 40–59 years) were included in the study. F8 genotyping revealed 20 different missense mutations. Patients received either recombinant (65%) or plasma‐derived FVIII concentrates (35%) by intermittent bolus injections (41%) or continuous infusion (57%). Two patients developed a low titre inhibitor post‐operatively. The incidence of inhibitor development following intensive treatment for surgery in this unselected prospective cohort of mild/moderate haemophilia A patients was 4% (95% confidence interval, 0·5–14·8).
Candidate gene polymorphisms and the risk for pregnancy‐related venous thrombosis
Authors: Dahm Anders E. A. , Bezemer Irene D. , Bergrem Astrid , Jacobsen Anne F. , Jacobsen Eva M. , Skretting Grethe , Rosendaal Frits R. , Sandset Per Morten
Published: April 2012

Venous thrombosis (VT) is one of the leading causes of maternal death in the western world, but the genetic causes of pregnancy‐relatedVTare insufficiently understood. The aim of this study was to investigate the association between common genetic variations in candidate genes and pregnancy‐relatedVT. We undertook a hospital based case–control study of women withVTduring pregnancy or puerperium; controls were women giving birth without havingVT. Single nucleotide polymorphisms (SNPs) were selected in 49 pre‐specified candidate genes involved in coagulation, inflammation, and hormonal metabolism in 313 cases and 353 controls. We found new associations betweenSNPs and total pregnancy‐relatedVTin the genes encoding coagulation factorsVandVIII, and p‐selectin. Additional new associations betweenSNPs and antenatalVTwere found in the genes encoding the epidermal growth factor receptor, the pregnaneXreceptor, and proteinS. Of 21SNPs previously associated with thrombotic disease, rs2289252 inF11and rs3917643 inF3were associated with pregnancy‐relatedVT, while rs4524 inF5was associated with antenatalVT.
Outcome disparities in multiple myeloma: a SEER‐based comparative analysis of ethnic subgroups
Authors: Ailawadhi Sikander , Aldoss Ibrahim T. , Yang Dongyun , Razavi Pedram , Cozen Wendy , Sher Taimur , Chanan‐Khan Asher
Published: April 2012

Studies of ethnic disparities in malignancies have revealed variation in clinical outcomes. In multiple myeloma (MM), previous literature has focused only on patients of Caucasian and African‐American (AA) descent. We present a Surveillance Epidemiology and End Results (SEER)‐based outcome analysis of MM patients from a broader range of ethnicities, representing current United States demographics. The SEER 17 Registry data was utilized to analyse adult MM patients diagnosed since 1992 (n = 37 963), as patients of other ethnicities were not well represented prior to that. Overall survival (OS) and myeloma‐specific survival (MSS) were compared across different ethnicities stratified by year of diagnosis, registry identification, age, sex and marital‐status. Hispanics had the youngest median age at diagnosis (65 years) and Whites had the oldest (71 years) (P < 0·001). Increased age at diagnosis was an independent predictor of decreased OS and MSS. Asians had the best median OS (2·7 years) and MSS (4·1 years), while Hispanics had the worst median OS (2·4 years). These trends were more pronounced in patients ≥75 years. Cumulative survival benefit over successive years was largest among Whites (1·3 years) and smallest among Asians (0·5 years). These disparities may be secondary to multifactorial causes that need to be explored and should be considered for optimal triaging of healthcare resources.
Diagnosis and management of chronic graft‐versus‐host disease
Authors: Dignan Fiona L. , Amrolia Persis , Clark Andrew , Cornish Jacqueline , Jackson Graham , Mahendra Prem , Scarisbrick Julia J. , Taylor Peter C. , Shaw Bronwen E. , Potter Michael N. ,   on behalf of the Haemato‐oncology Task Force of the British Committee for Standards in Haematology and the British Society for Blood and Marrow Transplantation
Published: April 2012

A joint working group established by the Haemato‐oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Society for Bone Marrow Transplantation (BSBMT) has reviewed the available literature and made recommendations for the diagnosis and management of chronic graft‐versus‐host disease (GvHD). This guideline includes recommendations for the diagnosis and staging of chronic GvHD as well as primary treatment and options for patients with steroid‐refractory disease. The goal of treatment should be the effective control of GvHD while minimizing the risk of toxicity and relapse.
Diagnosis and management of acute graft‐versus‐host disease
Authors: Dignan Fiona L. , Clark Andrew , Amrolia Persis , Cornish Jacqueline , Jackson Graham , Mahendra Prem , Scarisbrick Julia J. , Taylor Peter C. , Hadzic Nedim , Shaw Bronwen E. , Potter Michael N. ,   on behalf of the Haemato‐oncology Task Force of the British Committee for Standards in Haematology and the British Society for Blood and Marrow Transplantation
Published: April 2012

A joint working group established by the Haemato‐oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Society for Bone Marrow Transplantation (BSBMT) has reviewed the available literature and made recommendations for the diagnosis and management of acute graft‐versus‐host disease. This guideline includes recommendations for the diagnosis and grading of acute graft‐versus‐host disease as well as primary treatment and options for patients with steroid‐refractory disease. The goal of treatment should be effective control of graft‐versus‐host disease while minimizing risk of toxicity and relapse.
Success of allogeneic marrow transplantation for children with severe aplastic anaemia
Authors: Burroughs Lauri M. , Woolfrey Ann E. , Storer Barry E. , Deeg H. Joachim , Flowers Mary E. D. , Martin Paul J. , Carpenter Paul A. , Doney Kris , Appelbaum Frederick R. , Sanders Jean E. , Storb Rainer
Published: April 2012

Allogeneic marrow transplantation offers curative therapy for children with severe aplastic anaemia (SAA). We report the outcomes of 148 children with SAA who received human leucocyte antigen (HLA)‐matched related marrow grafts between 1971 and 2010. Patients were divided into three groups, reflecting changes in conditioning and graft‐versus‐host disease (GVHD) prophylaxis regimens that occurred over time. Patients in Group 1 were conditioned with cyclophosphamide (CY; 200 mg/kg) followed by ‘long' (102 d) methotrexate (MTX). Patients in Groups 2 and 3 received CY alone (Group 2) or combined with anti‐thymocyte globulin (Group 3) followed by ‘short’ (days 1, 3, 6, and 11) MTX and ciclosporin (until day 180). With a median follow‐up of 25 years, the 5‐year survivals were 66%, 95%, and 100% for Groups 1, 2, and 3, respectively (overall P < 0·0001). The 3‐year estimates of graft rejection were 22%, 32%, and 7%, respectively. The probabilities of grades III‐IV acute and 2‐year chronic GVHD were 15%, 0%, and 3%, and 21%, 21%, and 10%, respectively. Advances in preparative and GVHD prophylaxis regimens, and supportive care during the past 40 years have led to improved outcomes for children with SAA. These results confirm the use of allogeneic marrow transplantation for children with SAA who have HLA‐matched related donors.
Organ‐specific management and supportive care in chronic graft‐versus‐host disease
Authors: Dignan Fiona L. , Scarisbrick Julia J. , Cornish Jacqueline , Clark Andrew , Amrolia Persis , Jackson Graham , Mahendra Prem , Taylor Peter C. , Shah Pallav , Lightman Sue , Fortune Farida , Kibbler Christopher , Andreyev Jervoise , Albanese Assunta , Hadzic Nedim , Potter Michael N. , Shaw Bronwen E. ,   on behalf of the Haemato‐oncology Task Force of the British Committee for Standards in Haematology and the British Society for Blood and Marrow Transplantation
Published: April 2012

A joint working group established by the Haemato‐oncology subgroup of the British Committee for Standards in Haematology and the British Society for Bone Marrow Transplantation has reviewed the available literature and made recommendations for the supportive care and management of organ‐specific complications of chronic graft‐versus‐host disease (cGvHD). This guideline includes recommendations for the specific therapy of skin, oral, liver, gut, lung, ocular and genital manifestations of cGvHD and for the supportive care of these patients, including vaccinations and prophylaxis against infection. The goal of treatment should be effective control of GvHD while minimizing the risk of toxicity and relapse.
Temperature‐related shifts in butterfly phenology depend on the habitat
Authors: Altermatt Florian
Published: April 2012

Many species are becoming active earlier in the season as the climate becomes warmer. In parallel to phenological responses to climate change, many species have also been affected by habitat changes due to anthropogenic land use. As habitat type can directly affect microclimatic conditions, concurrent changes in climate and habitat could have interacting effects on the phenology of species. Temperature‐related shifts in phenology, however, have mostly been studied independent of habitat types. Here,Iused long‐term data from a highly standardized monitoring program with 519 transects to study how phenology of butterflies is affected by ambient temperature and habitat type.Icompared forests, agricultural areas and settlements, reflecting three major land use forms, and considered butterfly species that were observed in all three of these habitats. Seasonal appearance of the butterflies was affected both by the ambient temperature and the habitat type. As expected, warmer temperatures led to an overall advancement of the appearance and flight period of most species. Surprisingly, however, phenology of species was delayed in settlement habitats, even though this habitat type is generally associated with higher temperatures. A possible explanation is dispersal among habitat types, such that source–sink effects affect local phenology. When there is little productivity in settlement areas, observed butterflies may have immigrated from forest or agricultural habitats and thus appear later in settlements. My findings suggest that a spillover of individuals among habitats may affect phenology trends and indicate that phenological studies need to be interpreted in the context of habitat types. This becomes especially important when defining strategies to prevent or mitigate effects of climate and land‐use changes on phenology and abundance of species.
Simulating forest productivity along a neotropical elevational transect: temperature variation and carbon use efficiency
Authors: Marthews Toby R. , Malhi Yadvinder , Girardin Cécile A. J. , Silva Espejo Javier E. , Aragão Luiz E. O. C. , Metcalfe Daniel B. , Rapp Joshua M. , Mercado Lina M. , Fisher Rosie A. , Galbraith David R. , Fisher Joshua B. , Salinas‐Revilla Norma , Friend Andrew D. , Restrepo‐Coupe Natalia , Williams Richard J.
Published: April 2012

A better understanding of the mechanisms controlling the magnitude and sign of carbon components in tropical forest ecosystems is important for reliable estimation of this important regional component of the global carbon cycle. We used the
JULES
vegetation model to simulate all components of the carbon balance at six sites along an Andes‐Amazon transect across Peru and Brazil and compared the results to published field measurements. In the upper montane zone the model predicted a lack of forest vegetation, indicating a need for better parameterization of the responses of cloud forest vegetation within the model. In the lower montane and lowland zones simulated ecosystem productivity and respiration were predicted with reasonable accuracy, although not always within the error bounds of the observations. Model‐predicted carbon use efficiency in this transect surprisingly did not increase with elevation, but remained close to the ‘temperate’ value 0.5. Upper montane forests were predicted to allocate ~50% of carbon fixation to biomass maintenance and growth, despite available measurements showing that they only allocate ~33%. This may be explained by elevational changes in the balance between growth and maintenance respiration within the forest canopy, as controlled by both temperature‐ and pressure‐mediated processes, which is not yet well represented in current vegetation models.
Temporal variation in responses of species to four decades of climate warming
Authors: Mair Louise , Thomas Chris D. , Anderson Barbara J. , Fox Richard , Botham Marc , Hill Jane K.
Published: April 2012

Many species are expanding at their leading‐edge range boundaries in response to climate warming. Species are known to respond individualistically to climate change, but there has been little consideration of whether responses are consistent over time. We compared responses of 37 southerly distributed British butterflies over two study periods, first between 1970–1982 and 1995–1999 and then between 1995–1999 and 2005–2009, when mean annual temperature increased regionally by 0.03 °C yr−1 (a significant rate of increase) and 0.01 °C yr−1(a nonsignificant increase) respectively. Our study species might be expected to benefit from climate warming. We measured three responses to climate to investigate this; changes in range margin, distribution area and abundance. In general, the responses of species were inconsistent over time. Species that increased their distribution areas during the first period tended to do so again during the second period, but the relationship was weak. Changes in range margins and abundance were not consistent. In addition, only 5/37 species showed qualitatively similar responses in all three response variables over time (three species increased and two species declined in all variables in both periods). Overall rates of range expansion and distribution area change were significantly greater in the second study period, despite the lower rate of warming, perhaps due to species exploiting climate‐distribution lags remaining from the earlier, warmer period. However, there was a significantly greater decline in abundance during the second study period, so range expansions northwards were not necessarily accompanied by increases in distribution area and/or abundance. Hence, species ranges have been thinning as they have expanded northwards. The idiosyncratic responses of these species likely reflect the balance of climatic and habitat drivers of species distribution and abundance changes.
The potential role of synovial thrombomodulin in the pathophysiology of joint bleeds in haemophilia
Authors: DARGAUD Y. , SIMPSON H. , CHEVALIER Y. , SCOAZEC J. Y. , HOT A. , GUYEN O. , BAGLIN T. , NÉGRIER C.
Published: April 2012

Summary.  Haemophilic arthropathy (HA) is one of the main complications of recurrent bleeding episodes in patients with severe haemophilia. However, the precise reasons making joints the predilected site of bleeding in patients with haemophilia are not fully understood. The objective of this project was to study the potential effect of synovium‐derived thrombomodulin (TM) on the pathophysiology of haemarthroses. The concentration of TM and tissue factor pathway inhibitor (TFPI) was measured in knee synovial fluid of patients with haemophilia and controls. We used these concentrations of TM and TFPI in a thrombin generation (TG) model to analyse their in vitro effects on coagulation in plasma of six male controls and six severe haemophiliacs. The expression of TM in synovial tissue was also studied in controls and haemophiliacs. Patients with HA had significantly higher synovial fluid TFPI and TM levels, with a mean of 47 ± 27 ng/mL (P = 0.033) and 56 ± 25 ng/mL (P = 0.031), respectively, compared to the control group which presented lower levels of synovial fluid TFPI (26 ± 9 ng/mL) and TM concentrations (39 ± 21 ng/mL). TG capacity was significantly reduced in the presence of TM 56 ng/mL (P = 0.02), concentration observed in the synovial fluid of patients with HA. The concomitant addition of TM 56 ng/mL and TFPI 47 ng/mL induced a highly significant inhibition of TG in the same samples (P = 0.008).No significant inhibition of TG capacity was observed in the presence of control synovial concentration of TM (P > 0.05). Our results showed increased TM levels in synovial fluid and dramatically impaired expression of TM on synovial cells, suggesting a massive release of TM into the synovial fluid induced by a concerted action of neutrophils and cytokines on synovial cells as previously described in patients with rheumatoid arthritis.
Designing an effective trap cropping strategy: the effects of attraction, retention and plant spatial distribution
Authors: Holden Matthew H. , Ellner Stephen P. , Lee Doo‐Hyung , Nyrop Jan P. , Sanderson John P.
Published: April 2012

1. Trap cropping, the use of alternative host plants to reduce pest damage to a focal cash crop or other managed plant population, can be a sustainable strategy for pest control, but in practice it has often failed to reach management goals. Of the few successful trap cropping examples at a commercial scale, nearly all have included supplemental management strategies that reduce pest dispersal off the trap crop. In contrast, the trap cropping literature has focused extensively on trap plant attractiveness.

2. To test whether the dispersal of insects off trap plants is as important as the anecdotal evidence suggests, we developed a simple model to understand how a trap plant’s spatial configuration within a field, its attractiveness and its ability to retain pests affect pest density on a target cash crop.

3. The model predicts that when trap crop retention is low, trap cropping is ineffective, and small increases in retention offer little improvement. However, when retention is high, small differences in retention dramatically affect trap cropping efficacy. In contrast, when the attractiveness of a trap crop is high, further increases in attractiveness have little effect on trap cropping efficacy.

4. Placing trap plants close together is most often detrimental to pest management because it leaves large portions of the field without nearby traps. However, planting the trap crop in rows often does not clump the landscape enough to cause this detrimental effect.

5. Synthesis and applications. The predictions from our model confirm the anecdotal evidence that trap cropping failures may be attributed to a focus on attraction at the expense of retention. A very high retention rate is required for effective reduction of pest densities. Therefore, additional practices that prevent insects from dispersing back into the cash crop may be essential for effective trap cropping designs. These techniques include trap vacuuming, trap harvesting, sticky traps, planting a high proportion of trap plants or applications of pesticides or natural enemies to the trap crop.
Cognitive behavioural therapy from the perspective of clients with mild intellectual disabilities: a qualitative investigation of process issues
Authors: Pert C. , Jahoda A. , Stenfert Kroese B. , Trower P. , Dagnan D. , Selkirk M.
Published: April 2012

Background  Clinicians working with clients who have mild intellectual disabilities (IDs) have shown growing enthusiasm for using a cognitive behavioural approach, amid increasing evidence of good treatment outcomes for this client group. However, very little is known about the views and experiences of clients with IDs who have undergone cognitive behavioural therapy. This study aims to explore the perspective of these clients.

Methods  Fifteen participants with borderline to mild IDs and problems of anxiety, depression and anger were interviewed regarding their experience of cognitive behavioural therapy (CBT). Two semi‐structured interviews were carried out in the first phase of therapy between session four and session nine. An interpretive phenomenological approach was taken to seek out themes from participants' own personal accounts.

Results  Participants valued the opportunity to talk about problems with their therapist and benefitted from therapeutic relationships characterised by warmth, empathy and validation. Participants identified areas of positive change; however, many thought that this may be short lived or not maintained beyond discharge.

Conclusions  The supportive aspects of therapeutic relationships were particularly important to participants undergoing CBT. The clinical implications are considered.
Hypothalamic‐pituitary‐adrenal (HPA) axis activity in adults with intellectual disabilities: a preliminary investigation
Authors: Presland A. D. , Clare I. C. H. , Broughton S. , Luke L. , Wheeler E. , Fairchild G. , Watson P. C. , Chan W. Y. S. , Kearns A. , Ring H. A.
Published: April 2012

Background  Cortisol is a marker of physiological arousal, exhibiting a characteristic pattern of diurnal activity. The daily cortisol profile has been examined extensively and is atypical in a number of clinical disorders. However, there are very few studies focussing on the cortisol profile in adults with intellectual disabilities (ID). This paper reports a preliminary investigation into the nature of the cortisol profile in adults with mild or moderate ID and provides reflections on the challenges of psychophysiological research in this population.

Methods  On two consecutive days, 39 adults with mild or moderate ID each donated saliva samples for cortisol analysis, at multiple times between waking and evening. A comparison between these data and the published literature permitted a descriptive assessment of the cortisol awakening response (CAR) and diurnal profile. A variety of psychometric measures and an assessment of behavioural history were also collected in order to describe aspects of the participants' emotional and behavioural states.

Results  Individuals with ID exhibit a diurnal cortisol secretion profile, qualitatively similar to that of the typical, healthy, adult population. However, the findings also suggested a blunted CAR, warranting further investigation. There was also some evidence that cortisol secretion was affected by anxiety and a recent history of aggression.

Conclusion  While further work is required to characterise the CAR fully, there was no indication that the diurnal cortisol profile among people with ID differs from that of the typical population. This study also demonstrates that, although challenging, it is feasible, and acceptable to participants, to collect repeated physiological measures from men and women with mild and moderate ID.
Service user involvement in nurse education: perceptions of mental health nursing students
Authors: O' DONNELL H. , GORMLEY K.
Published: April 2012

Accessible summary

Professional education and policy strategies increasingly stress the need for service users to be involved in the education of all nursing students, including students undertaking mental health field programmes.

In this study, a sample of recently graduated mental health nursing students, are asked to describe their perceptions of increased service user involvement in mental health nursing programmes.

The findings of the study demonstrated that recently graduated students were supportive of service user involvement. Study participants recognize the value of this involvement, the need to protect users who may be vulnerable and the clear benefits to both personal and service development, which will result from increased user engagement.

Increasingly providers of mental health nurse education are required to demonstrate user involvement in all aspects of these programmes including student selection, programme design and student assessment. There has been limited analysis of how nursing students perceive user involvement in nurse education programmes. The aim of this study has been to explore mental health nursing student's perceptions of involving users in all aspects of pre‐registration mental health nursing programme. Researchers completed a number of focus group interviews with 12 ex‐mental health nursing students who had been recruited by purposeful sampling. Each focus group interview was recorded and analysed using a series of data reduction, data display and verification methods. The study confirms many of the findings reported in earlier user participation in education studies. Three main themes related to user involvement have been identified: the protection of users, enhanced student learning and the added value benefits associated with user involvement.
Bioequivalence in dogs of a meloxicam formulation administered as a transmucosal oral mist with an orally administered pioneer suspension product
Authors: LEES P. , CHENG Z. , KEEFE T. J. , WEICH E. , BRYD J. , CEDERGREN R. , COZZI E.
Published: April 2012

Lees, P., Cheng, Z., Keefe, T. J., Weich, E., Bryd, J., Cedergren, R., Cozzi, E. Bioequivalence in dogs of a meloxicam formulation administered as a transmucosal oral mist with an orally administered pioneer suspension product.J. vet. Pharmacol. Therap. 36, 78–84.

A mucosal mist formulation of meloxicam, administered as a spray into the mouth (test article), was compared for bioequivalence to a pioneer meloxicam suspension for oral administration (reference article). Pharmacokinetic profiles and average bioequivalence were investigated in 20 dogs. The study design comprised a two‐period, two‐sequence, two‐treatment cross‐over design, with maximum concentration (Cmax) and area under plasma concentration–time curve to last sampling time (AUClast) used as pivotal bioequivalence variables. Bioequivalence of the products was confirmed, based on relative ratios of geometric mean concentrations (and 90% confidence intervals within the range 0.80–1.25) forCmaxof 101.9 (97.99–106.0) and for AUClastof 97.24 (94.44–100.1). The initial absorption of meloxicam was more rapid for the test article, despite virtually identicalCmaxvalues for the two products. Mean elimination half‐lives were 29.6 h (test article) and 30.0 h (reference article). The meloxicam plasma concentration–time profiles were considered in relation to published data on the inhibition of the cyclooxygenase‐1 (COX‐1) and COX‐2 isoenzymes by meloxicam.
Serial Examination of Serum IL‐8, IL‐10 and IL‐1Ra Levels is Significant in Neonatal Seizures Induced by Hypoxic–Ischaemic Encephalopathy1
Authors: Youn Y. A. , Kim S. J. , Sung I. K. , Chung S. Y. , Kim Y. H. , Lee I. G.
Published: April 2012

We investigated changes in the levels of significant cytokines in relation to neonatal seizures, a pattern of cytokine concentrations serially and the severity of brain insult. The hypoxic–ischaemic encephalopathy‐induced seizure group consisted of 13 patients, and another 15 normal newborns were enrolled as a control group. All of the initial samples were obtained within the first 24 h of admission, and the second samples were obtained between 48 and 72 h in both groups. Only the third samples were taken in the seizure group on the 5th day. During neonatal seizures, the levels of most cytokines increased within 24 h, and, in particular, the levels of interleukin (IL)‐8 significantly increased (P < 0.05). After 48–72 h of seizure onset, the levels of most cytokines decreased, especially, IL‐1Ra; however, IL‐8 and IL‐10 remained increased (P < 0.05). During the prognosis, one patient who was diagnosed with quadriplegic cerebral palsy at 6 months of age presented extreme elevation of IL‐1beta, IL‐1Ra, IL‐6, IL‐8, IL‐10 and tumor necrosis factor‐alpha in the initial sample, reflecting the severity of brain damage. A significant increase in IL‐8 may serve as a biomarker for earlier detection of brain damage in neonatal seizure, if detected within 24 and 48–72 h of the seizure.
Association between Arachidonate 5‐Lipoxygenase‐Activating Protein (ALOX5AP) and Lung Function in a Korean Population
Authors: Ro M. , Kim S. , Pyun J.‐A. , Shin C , Cho N. H , Lee J.‐Y , Koh I. , Kwack K
Published: April 2012

Arachidonate 5‐lipoxygenase‐activating protein (ALOX5AP) plays a role in the 5‐lipoxygenase (LO) pathway, which includes the LTC4, LTD4, LTE4 and LTB4. These leukotrienes are known causative factors of asthma, allergy, atopy and cardiovascular diseases. ALOX5AP lacks enzyme activity and acts by helping 5‐LO function. In this study, healthy and general subjects who live in rural and urban areas of Korea were tested for the association of ALOX5AP polymorphisms with lung function. Lung function was also estimated by calculating the predicted values for forced expiratory volume in one second (FEV1_%PRED) and the proportion of the forced vital capacity exhaled in the first second (FEV1/FVC_PRED). The linear regression was adjusted for residence area, gender, age, height and smoking status. The analysis revealed associations between FEV1 and the single‐nucleotide polymorphism (SNP) rs9506352 and the haplotype TCAC (permuted P‐value < 0.05). The linkage disequilibrium block that included the significant SNPs overlapped with SNPs that were revealed previously to associate with myocardial infarction and asthma and to affect lung function. This study is the first to demonstrate the association between lung function and ALOX5AP polymorphisms in a healthy and general population.
American Tegumentary Leishmaniasis: Cytokines and Nitric Oxide in Active Disease and After Clinical Cure, With or Without Chemotherapy
Authors: Souza M. A. , Castro M. C. A. B. , Oliveira A. P. , Almeida A. F. , Reis L. C. , Silva C. J. , Brito M. E. F. , Pereira V. R. A.
Published: April 2012

The influence of immune response on the treatment of American tegumentary leishmaniasis is pointed by several authors, and the existence of protective immunity in self‐healed patients (SH) is also suggested. Thus, interferon‐gamma (IFN‐γ), tumour necrosis factor‐alpha (TNF‐α), interleukin (IL‐) 10, IL‐17, IL‐22 and nitric oxide (NO) production was determined in PBMC culture supernatants from patients with active disease (AD) and after therapy, SH patients and healthy subjects, in response to the soluble antigen of Leishmania (Viannia) braziliensis. It was demonstrated that, during the active disease, there is a predominance of IFN‐γ and TNF‐α, indicating a proinflammatory phase of the response; IL‐17 is also highlighted at this clinical state. Also, TNF‐α was slightly increased in patients after therapy. NO secretion was noticed in SH individuals, while IL‐17 appeared in low levels in these patients and seems to be regulated by NO. The presence of IL‐10 was observed in all groups of patients. From this study, we can suggest that in the active disease and after clinical cure, with or without chemotherapy, specific cellular immunity takes part against Leishmania, but with some similarities between the clinical states. Thus, it indicates that the mediators herein described are necessary for the cure to occur.
Comparison of pre‐cryopreserved and post‐thaw‐and‐wash‐nucleated cell count on major outcomes following unrelated cord blood transplant in children
Authors: McManus Meghann Pine , Wang Li , Calder Cassie , Manes Becky , Evans Misty , Bruce Kathryn , Ho Richard H. , Domm Jennifer , Frangoul Haydar
Published: April 2012

McManus MP, Wang L, Calder C, Manes B, Evans M, Bruce K, Ho RH, Domm J, Frangoul H. Comparison of pre‐cryopreserved and post‐thaw‐and‐wash‐nucleated cell count on major outcomes following unrelated cord blood transplant in children.

Abstract:  Engraftment and OS after umbilical CBT is highly dependent on the TNC. The contribution of the wash step to cell loss and ultimately the dose of cells available for transplant is not well described. To investigate the amount of cell loss after washing and its impact on major outcomes compared to pre‐cryopreserved TNC, we analyzed data from patients prospectively enrolled on a National Heart, Lung and Blood Institute sponsored cord blood transplant study between 1999 and 2003. There were 310 patients ≤18 yr of age with malignant (N = 218) or non‐malignant (N = 92) disease enrolled on this trial. Only single CBU were used. All CBU were thawed and washed using an identical process. The median TNC after thawing and washing (PTW) was 5.43 × 107/kg (79% recovery of cells). The cumulative incidence of neutrophil engraftment was significantly higher in patients receiving a PTW TNC ≥2.5 × 107/kg (p = 0.01). The cumulative incidence of TRM was higher among patients receiving post‐thaw‐and‐wash TNC <2.5 × 107/kg (p = 0.039). In conclusion, receiving a PTW TNC of <2.5 × 107/kg resulted in worse neutrophil engraftment and increased transplant‐related mortality compared to a PTW TNC of ≥2.5 × 107/kg.
Respiratory syncytial virus lower respiratory tract infection in a pediatric liver transplant recipient treated with oral ribavirin
Authors: Keck Megan , Mindru Cezarina , Kalil Andre C. , Mercer David F. , Florescu Diana F.
Published: April 2012

Keck M, Mindru C, Kalil AC, Mercer DF, Florescu DF. Respiratory syncytial virus lower respiratory tract infection in a pediatric liver transplant recipient treated with oral ribavirin.

Abstract:  The mainstay of therapy for RSV disease is supportive care, although aerosolized ribavirin has been used to treat infants and young children with severe lower respiratory tract infections. Aerosolized ribavirin has adverse effects, high cost and teratogenic potential. We report the case of a pediatric liver transplant recipient diagnosed with lower respiratory RSV infection, who was successfully treated with oral ribavirin.
Teamwork, pleasure and bargaining in animal social behaviour
Authors: ROUGHGARDEN J.
Published: April 2012

Intimate behaviour between animals is hypothesized to enable teamwork. The pleasure experienced in grooming, preening, dancing, mating and singing in synchrony is hypothesized to motivate participants to coordinate actions directed towards a shared goal that enhances each individual's fitness. This cooperative behaviour evolves as a mutual direct benefit, not as altruism. Teamwork leads to an equilibrium set of returns to the participants that may be modelled as a Nash bargaining solution instead of as the more familiar Nash equilibrium. The dynamics leading to that equilibrium may be modelled based on joint action instead of the more familiar individualistic action. Confusions by Binmore (J. Evol. Biol. 2010; 23: 1351) about this hypothesis are corrected.
Intra‐specific variation in the morphology and the benefit of large genital sclerites of males in the adzuki bean beetle (Callosobruchus chinensis)
Authors: SAKURAI G. , HIMURO C. , KASUYA E.
Published: April 2012

Rapid evolution has led to a large diversity in the sizes and morphology of male genitals across taxa, but the mechanisms driving this evolution remain controversial. In this study, we investigated the function of male genital sclerites in the adzuki bean beetle (Callosobruchus chinensis) and compared the length and morphology of genital sclerites between two populations that vary in their degree of polyandry. We found that the length of male genital sclerites was negatively correlated with copulation duration but positively correlated with the speed of matings with multiple females. Additionally, we found that the average length and number of genital sclerite spines of males from the more polyandrous population were larger than those from the less polyandrous population. We suggest that the genital sclerite of male adzuki bean beetles evolved by sexual selection, and a larger genital sclerite has a selective advantage because it allows for rapid copulations with multiple females.
Cell surface hydrophobicity of oral Candida dubliniensis isolates following limited exposure to sub‐therapeutic concentrations of chlorhexidine gluconate
Authors: Ellepola Arjuna N. B. , Joseph Bobby K. , Khan Z. U.
Published: April 2012

Candidal adhesion has been implicated as the initial step in the pathogenesis of oral candidiasis and cell surface hydrophobicity (CSH) has been implicated in adhesion to mucosal surfaces. Candida dubliniensis is an opportunistic pathogen associated with recurrent oral candidiasis. Chlorhexidine gluconate is by far the commonest antiseptic mouth wash prescribed in dentistry. At dosage intervals the intraoral concentration of this antiseptic fluctuates considerably and reaches sub‐therapeutic levels due to the dynamics of the oral cavity. Hence, the organisms undergo only a limited exposure to the antiseptic during treatment. The impact of this antiseptic following such exposure on CSH of C. dubliniensis isolates has not been investigated. Hence, the main objective of this study was to investigate the effect of brief exposure to sub‐therapeutic concentrations of chlorhexidine gluconate on the CSH of C. dubliniensis isolates. Twelve oral isolates of C. dubliniensis were briefly exposed to three sub‐therapeutic concentrations of 0.005%, 0.0025% and 0.00125% chlorhexidine gluconate for 30 min. Following subsequent removal of the drug, the CSH of the isolates was determined by a biphasic aqueous‐hydrocarbon assay. Compared with the controls, exposure to 0.005% and 0.0025% chlorhexidine gluconate suppressed the relative CSH of the total sample tested by 44.49% (P < 0.001) and 21.82% (P < 0.018), respectively, with all isolates being significantly affected. Although exposure to 0.00125% of chlorhexidine gluconate did not elicit a significant suppression on the total sample tested (7.01%; P > 0.05), four isolates of the group were significantly affected. These findings imply that exposure to sub‐therapeutic concentrations of chlorhexidine gluconate may suppress CSH of C. dublinienis isolates, thereby reducing its pathogenicity and highlights further the pharmacodynamics of chlorhexidine gluconate.