Racial disparities in the treatment of endometrial intraepithelial neoplasia in postmenopausal women.

Disparities in endometrial cancer has increased during the past decade with Black women more likely to be diagnosed at a later stage and have higher mortality. The majority of research has been focused on cultural barriers, socioeconomic status, lack of access to care, comorbidities, and tumor histology to explain these disparities. Limited studies have been conducted on the disparity in the treatment of endometrial intraepithelial neoplasia(EIN). We sought to analyze the differences in treatment used in the management of postmenopausal women with EIN to evaluate whether race/ethnicity is a contributing factor. An IRB approved retrospective study was conducted amongst women at a single institution diagnosed with EIN. Ethnicity/race was defined as non-Hispanic White, non-Hispanic Black, Hispanic, and Asian. Demographic and clinical data was extracted. Multivariable logistic regression was used to examine the association between ethnicity/race and treatment, adjusted for age, BMI, and underlying medical conditions such as cardiovascular disease and diabetes. In total, 254 patients were analyzed. A significant association between ethnicity/race and treatment with non-Hispanic Black women less likely to be treated with surgical management compared to non-Hispanic White women (OR = 0.326, 95 %CI 0.129-0.827, p = 0.026). Importantly, after adjusting for clinical risk factors(age, BMI, CVD, diabetes), non-Hispanic Black women remained at an increased risk of not undergoing surgical intervention (OR = 0.333, 95 % CI 0.125-0.882, p = 0.027). Future research is imperative to evaluate the root cause of this disparity in the healthcare system.

Optimizing electronic blood ordering and supporting administration workflows to improve blood utilization in the pediatric hospital setting.

BACKGROUND: Red blood cell wastage occurs when blood is discarded rather than transfused, and ineffective ordering results in unnecessary crossmatch procedures. We describe how a multimodal approach to redesigning electronic ordering tools improved blood utilization in a pediatric inpatient setting and how using innovative application of time series data analysis provides insights into intervention effectiveness, which can guide future process improvement cycles. METHODS: A multidisciplinary team used best practices and Toyota Production System methodology to redesign electronic blood ordering and improve administration processes. We analyzed crossmatch to transfusion ratio and red blood cell wastage time series data extracted from our laboratory information system and electronic health record. We used changepoint analysis to identify statistically discernible breaks in each time series, compatible with known interventions. We performed causal impact analysis on red blood cell wastage time series data to estimate blood wastage avoided due to the interventions. RESULTS: Changepoint analysis estimated an 11% decrease in crossmatch to transfusion ratio and a 77% decrease in red blood cell monthly wastage rate during the intervention period. Causal impact analysis estimated a 61% reduction in expected wastage compared to the scenario if the interventions had not occurred. DISCUSSION: Our results show that electronic health record design is an important factor in reducing waste and preventing unnecessary crossmatching, and that time series analysis can be a useful tool for evaluating the long-term impact of each stage of intervention in a longitudinal process redesign effort for the purpose of effectively targeting future improvement efforts.

Perioperative management of patients with congenital or acquired disorders of the QT interval.

QT prolongation can be attributable to various causes that can be categorised as acquired or congenital. Arrhythmias related to QT prolongation can result in clinical presentations, such as syncope and sudden cardiac death. The perioperative period presents a number of issues that may affect a patient's risk of developing polymorphic ventricular tachycardia or torsades de pointes. Although most patients may have an unremarkable perioperative course, some may have complications; this review article aims to help clinicians avoid potential complications, and to help them address treatment for perioperative issues that may occur.

Body esteem, peer difficulties and perceptions of physical health in overweight and obese urban children aged 5 to 7 years.

OBJECTIVE: To determine whether there is an association between body mass index (BMI) and body esteem in young overweight and obese urban children, and to test peer relationship difficulties and perceived physical health as mediators of this relationship. METHODS: Child self-reported body esteem, and parent-reported child peer relationship difficulties (being bullied by peers and peer rejection) and physical health perceptions were obtained from 218 overweight and obese children aged 5-7 years (81% racial/ethnic minority, M BMI = 25.3) and their primary caregivers. RESULTS: Higher BMI was associated with lower body esteem for both girls and boys. This relation was mediated by poor physical health for boys but not for girls. Peer relationship difficulties did not mediate the observed association between BMI and body esteem in either group; however, girls with higher BMI experienced more bullying and being bullied by peers was associated with lower body esteem in girls. CONCLUSIONS: Intervening with perceptions of physical health may buffer overweight and obese boys from developing low body esteem in early childhood.

Dietitians and eating disorders: an international issue.

The prevalence of eating disorders is higher in university nutrition faculties than in other faculties. We examined beliefs about and approaches to eating disorders in nutrition education faculties around the world. We developed a questionnaire specifically for this project and distributed 664 copies electronically, using contact information obtained in collaboration with Dietitians of Canada and the International Confederation of Dietetic Associations. Using the 101 questionnaires returned from 14 countries, we found that 77% of respondents felt eating disorders are a concern among nutrition students; however, only 15% of programs had policies/procedures to help address these disorders. Forty-eight percent of respondents thought screening for eating disorders would be a good idea; however, 78% of them believed screening would involve ethical issues. In conclusion, eating disorders are a concern in nutrition faculties around the world, and while most feel something should be done, ethical dilemmas contribute to confusion over the best approach. More work is needed in this area.

Current controversies in the use of haemoglobin A1c.

Haemoglobin A(1c) (HbA(1c)) has recently been adopted by the World Health Organization into its recommended criteria for diabetes diagnosis. Much debate continues regarding the relative benefits and potential disadvantages surrounding the use of HbA(1c) for this purpose. There is a lack of consensus as to whether this alteration to the definition of diabetes is a step forward or whether it could add further confusion and ambiguity to the debate on the method and criteria for the diagnosis of this globally important disease. This review provides a comprehensive overview of the current issues surrounding how HbA(1c) is measured and reported; and of the evidence for and against its use in diagnosis.

Identifying and reducing AFLP genotyping error: an example of tradeoffs when comparing population structure in broadcast spawning versus brooding oysters.

Phylogeographic inferences about gene flow are strengthened through comparison of co-distributed taxa, but also depend on adequate genomic sampling. Amplified fragment length polymorphisms (AFLPs) provide a rapid and inexpensive source of multilocus allele frequency data for making genomically robust inferences. Every AFLP study initially generates markers with a range of locus-specific genotyping error rates and applies criteria to select a subset for analysis. However, there has been very little empirical evaluation of the best tradeoff between culling all but the lowest-error loci to minimize overall genotyping error versus the potential for increasing population genetic signal by retaining more loci. Here, we used AFLPs to compare population structure in co-distributed broadcast spawning (Crassostrea virginica) and brooding (Ostrea equestris) oyster species. Using existing methods for almost entirely automated marker selection and scoring, genotyping error tradeoffs were evaluated by comparing results across a nested series of data sets with mean mismatch errors of 0, 1, 2, 3, 4 and >4%. Artifactual population structure was diagnosed in high-error data sets and we assessed the low-error point at which expected population substructure signal was lost. In both species, we identified substructure patterns deemed to be inaccurate at average mismatch error rates 2 and >4%. In the species comparison, the optimum data sets showed higher gene flow for the brooding oyster with more oceanic salinity tolerances. AFLP tradeoffs may differ among studies, but our results suggest that important signal may be lost in the pursuit of 'acceptable' error levels and our procedures provide a general method for empirically exploring these tradeoffs.

Overcoming the barriers experienced in conducting a medication trial in adults with aggressive challenging behaviour and intellectual disabilities.

BACKGROUND: Aggressive challenging behaviour in people with intellectual disability (ID) is frequently treated with antipsychotic drugs, despite a limited evidence base. METHOD: A multi-centre randomised controlled trial was undertaken to investigate the efficacy, adverse effects and costs of two commonly prescribed antipsychotic drugs (risperidone and haloperidol) and placebo. RESULTS: The trial faced significant problems in recruitment. The intent was to recruit 120 patients over 2 years in three centres and to use a validated aggression scale (Modified Overt Aggression Scale) score as the primary outcome. Despite doubling the period of recruitment, only 86 patients were ultimately recruited. CONCLUSIONS: Variation in beliefs over the efficacy of drug treatment, difficulties within multidisciplinary teams and perceived ethical concerns over medication trials in this population all contributed to poor recruitment. Where appropriate to the research question cluster randomised trials represent an ethically and logistically feasible alternative to individually randomised trials.

The NRG1 gene is frequently silenced by methylation in breast cancers and is a strong candidate for the 8p tumour suppressor gene.

Neuregulin-1 (NRG1) is both a candidate oncogene and a candidate tumour suppressor gene. It not only encodes the heregulins and other mitogenic ligands for the ERBB family, but also causes apoptosis in NRG1-expressing cells. We found that most breast cancer cell lines had reduced or undetectable expression of NRG1. This included cell lines that had translocation breaks in the gene. Similarly, expression in cancers was generally comparable to or less than that in various normal breast samples. Many non-expressing cell lines had extensive methylation of the CpG island at the principal transcription start site at exon 2 of NRG1. Expression was reactivated by demethylation. Many tumours also showed methylation, whereas normal mammary epithelial fragments had none. Lower NRG1 expression correlated with higher methylation. Small interfering RNA (siRNA)-mediated depletion of NRG1 increased net proliferation in a normal breast cell line and a breast cancer cell line that expressed NRG1. The short arm of chromosome 8 is frequently lost in epithelial cancers, and NRG1 is the most centromeric gene that is always affected. NRG1 may therefore be the major tumour suppressor gene postulated to be on 8p: it is in the correct location, is antiproliferative and is silenced in many breast cancers.

Neuroleptics in the treatment of aggressive challenging behaviour for people with intellectual disabilities: a randomised controlled trial (NACHBID).

OBJECTIVE(S): To assess the effects and cost-effectiveness of haloperidol, risperidone and placebo on aggressive challenging behaviour in adults with intellectual disability. DESIGN: A double-blind randomised controlled trial of two drugs and placebo administered in flexible dosage, with full, independent assessments of aggressive and aberrant behaviour, global improvement, carer burden, quality of life and adverse drug effects at baseline, 4, 12 and 26 weeks, and comparison of total care costs in the 6 months before and after randomisation. At 12 weeks, patients were given the option of leaving the trial or continuing until 26 weeks. Assessments of observed aggression were also carried out with key workers at weekly intervals throughout the trial. SETTING: Patients were recruited from all those being treated by intellectual disability services in eight sites in England, one in Wales and one in Queensland, Australia. PARTICIPANTS: Patients from all severity levels of intellectual disability; recruitment was extended to include those who may have been treated with neuroleptic drugs in the past. EXCLUSION CRITERIA: treatment with depot neuroleptics/another form of injected neuroleptic medication within the last 3 months; continuous oral neuroleptic medication within the last week; those under a section of the Mental Health Act 1983 or Queensland Mental Health Act 2000. INTERVENTIONS: Randomisation to treatment with haloperidol (a typical neuroleptic drug), risperidone (an atypical neuroleptic drug) or placebo using a permuted blocks procedure. Dosages were: haloperidol 1.25-5.0 mg daily; risperidone 0.5-2.0 mg daily. MAIN OUTCOME MEASURES: Primary: reduction in aggressive episodes between baseline and 4 weeks using Modified Overt Aggression Scale. Secondary: Aberrant Behaviour Checklist; Uplift/Burden Scale; 40-item Quality of Life Questionnaire; Udvalg for Kliniske Undersøgelser scale; Clinical Global Impressions scale. Economic costs recorded using a modified version of Client Service Receipt Inventory for 6 months before and after randomisation. RESULTS: There were considerable difficulties in recruitment because of ethical and consent doubts. Twenty-two clinicians recruited a total of 86 patients. Mean daily dosages were 1.07 mg rising to 1.78 mg for risperidone and 2.54 mg rising to 2.94 mg for haloperidol. Aggression declined dramatically with all three treatments by 4 weeks, with placebo showing the greatest reduction (79%, versus 57% for combined drugs) (p = 0.06). Placebo-treated patients showed no evidence of inferior response in comparison to patients receiving neuroleptic drugs. An additional study found that clinicians who had not participated in clinical trials before were less likely to recruit. Mean total cost of accommodation, services, informal care and treatment over the 6 months of the trial was 16,336 pounds for placebo, 17,626 pounds for haloperidol and 18,954 pounds for risperidone. CONCLUSIONS: There were no significant important benefits conferred by treatment with risperidone or haloperidol, and treatment with these drugs was not cost-effective. While neuroleptic drugs may be of value in the treatment of aggressive behaviour in some patients with intellectual disability, the underlying pathology needs to be evaluated before these are given. The specific diagnostic indications for such treatment require further investigation. Prescription of low doses of neuroleptic drugs in intellectual disability on the grounds of greater responsiveness and greater liability to adverse effects also needs to be re-examined.

Utilisation of inorganic salts in fungal crop disease management in the U.K.

The overaLl aim of the study described in this communication was to utilise the findings of a global scientific and technical literature survey on the use of inorganic salts against crop fungal diseases in order to assess the potential of using these substances to reduce the reliance of UK growers on conventional fungicides. A summary of the main findings of the Literature survey is provided followed by information on the current commercial use of inorganic salt-based products in fungal disease management. Finally, the scope of potential use of inorganic salts on high disease risk crops in the UK is assessed and specific crop/pathogen combinations are prioritised for further research.

Search for Lorentz and CPT violation effects in Muon spin precession.

The spin precession frequency of muons stored in the (g-2) storage ring has been analyzed for evidence of Lorentz and CPT violation. Two Lorentz and CPT violation signatures were searched for a nonzero delta omega a(=omega a mu+ - omega a mu-) and a sidereal variation of omega a mu+/-). No significant effect is found, and the following limits on the standard-model extension parameters are obtained: bZ = -(1.0+/-1.1) x 10(-23) GeV; (m mu dZ0 + HXY)=(1.8+/-6.0) x 10(-23) GeV; and the 95% confidence level limits b perpendicular mu+ <1.4 x 10(-24) GeV and b perpendicular mu- <2.6 x 10(-24) GeV.

Inorganic salts for suppressing powdery mildew in cucurbits--a worldwide survey.

The present review provides an update of recent progress in the use of inorganic salts to manage powdery mildew (Sphaerotheca fuliginea and Erysiphe cichoracearum) in cucurbits (Cucurbitaceae). A literature survey identified 16 salts, mainly bicarbonates (e.g. KHCO3), phosphates (e.g. K2HPO4) and silicates (e.g. Na2SiO3), as having potential to suppress powdery mildew in cucurbits. The percentage suppression compared with untreated controls was calculated from the best treatment of each of 20 peer-reviewed studies and this ranged from 41-99%. The high efficacy of inorganic salts in suppressing cucurbit powdery mildew coupled with the abundance of formulated inorganic salt-based products may enable a reduction in the number of conventional fungicide applications needed to control the disease. Overall, the survey revealed that spray or hydroponic applications of inorganic salts can be a useful component in the integrated management of cucurbit powdery mildew, leading to potential environmental and financial benefits.

Symptoms of dementia among adults with Down's syndrome: a qualitative study.

BACKGROUND: Dementia is common among adults with Down's syndrome (DS); yet the diagnosis of dementia, particularly in its early stage, can be difficult in this population. One possible reason for this may be the different clinical manifestation of dementia among people with intellectual disabilities. AIMS: The aim of this study was to map out the carers' perspective of symptoms of dementia among adults with DS in order to inform the development of an informant-rated screening questionnaire. METHOD: Unconstrained information from carers of people with DS and dementia regarding the symptoms, particularly the early symptoms of dementia, was gathered using a qualitative methodology. Carers of 24 adults with DS and dementia were interviewed. The interviews were recorded and fully transcribed. The transcripts were then analysed using qualitative software. RESULTS: There appeared to be many similarities in the clinical presentation of dementia in adults with DS and the non-intellectually disabled general population. Like in the non-intellectually disabled general population, forgetfulness especially, impairment of recent memory combined with a relatively intact distant memory and confusion were common, and presented early in dementia among adults with DS. However, many 'frontal lobe'-related symptoms that are usually manifested later in the process of dementia among the general population were common at an early stage of dementia among adults with DS. A general slowness including slowness in activities and speech, other language problems, loss of interest in activities, social withdrawal, balance problems, sleep problems, loss of pre-existing skills along with the emergence of emotional and behaviour problems were common among adults with DS in our study. CONCLUSIONS: This study highlights the similarities in the clinical presentation of dementia among the general population and people with DS with a particular emphasis on the earlier appearance of symptoms associated with the frontal lobe dysfunction among adults with DS.

Improved measurement of the positive-muon lifetime and determination of the Fermi constant.

The mean life of the positive muon has been measured to a precision of 11 ppm using a low-energy, pulsed muon beam stopped in a ferromagnetic target, which was surrounded by a scintillator detector array. The result, tau(micro)=2.197 013(24) micros, is in excellent agreement with the previous world average. The new world average tau(micro)=2.197 019(21) micros determines the Fermi constant G(F)=1.166 371(6)x10(-5) GeV-2 (5 ppm). Additionally, the precision measurement of the positive-muon lifetime is needed to determine the nucleon pseudoscalar coupling g(P).

Quantitative Fusarium spp. and Microdochium spp. PCR assays to evaluate seed treatments for the control of Fusarium seedling blight of wheat.

AIMS: To develop sensitive quantitative PCR assays for the two groups of pathogens responsible for Fusarium seedling blight in wheat: Fusarium group (Fusarium culmorum and Fusarium graminearum) and Microdochium group (Microdochium nivale and Microdochium majus); and to use the assays to assess performance of fungicide seed treatments against each group. METHODS AND RESULTS: Primers conserved between the species within each group were used to develop competitive PCR assays and used to quantify DNA of each group in wheat seed produced from inoculated field plots. Seed was used in seed treatment efficacy field experiments and the amount of DNA of each group was determined in emerged seedlings. The performance of treatments towards each group of pathogens was evaluated by comparison of the reduction in DNA in seedlings emerged from treated seed compared with untreated seed. CONCLUSIONS: DNA from the two groups of pathogens causing Fusarium seedling blight of wheat can be quantified separately using the competitive PCR assays. These assays show improved sensitivity compared with those previously reported for the individual species and allowed the quantification of pathogen DNA in seed and seedlings. Significant reductions in pathogen DNA were evident for each seed treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: Quantification of DNA for each group allows the evaluation of seed treatment performance towards the two components of Fusarium seedling blight disease complex. The approach taken and the assays developed in this study will be of use for the study of other Fusarium disease complexes and their control. Based on the results reported here on the seedling stage of crop development, further studies that examine the control of seed-borne pathogens through fungicide seed treatments throughout the growing season are warranted.

Hyperproliferation of PKD1 cystic cells is induced by insulin-like growth factor-1 activation of the Ras/Raf signalling system.

Autosomal dominant polycystic kidney disease (ADPKD) largely results from mutations in the PKD1 gene leading to hyperproliferation of renal tubular epithelial cells and consequent cyst formation. Rodent models of PKD suggest that the multifunctional hormone insulin-like growth factor-1 (IGF-1) could play a pathogenic role in renal cyst formation. In order to test this possibility, conditionally immortalized renal epithelial cells were prepared from normal individuals and from ADPKD patients with known germline mutations in PKD1. All patient cell lines had a decreased or absence of polycystin-1 but not polycystin-2. These cells had an increased sensitivity to IGF-1 and to cyclic AMP, which required phosphatidylinositol-3 (PI3)-kinase and the mitogen-activated protein kinase, extracellular signal-regulated protein kinase (ERK) for enhanced growth. Inhibition of Ras or Raf abolished the stimulated cell proliferation. Our results suggest that haploinsufficiency of polycystin-1 lowers the activation threshold of the Ras/Raf signalling system leading to growth factor-induced hyperproliferation. Inhibition of Ras or Raf activity may be a therapeutic option for decreasing tubular cell proliferation in ADPKD.

Identification of transmembrane proteins as potential prognostic markers and therapeutic targets in breast cancer by a screen for signal sequence encoding transcripts.

This study demonstrates, through a combination of stringent screening methods and thorough validation, that it is possible to identify transmembrane proteins preferentially expressed in primary breast tumour cells. mRNA was extracted from tumour cells isolated from invasive breast cancers and it was then subtracted against normal breast tissue mRNA prior to the generation of a signal sequence-trap library. Screening of the library identified 31 positive clones encoding 12 cell-surface and 12 secreted proteins. The expression of a subset of transmembrane genes was then interrogated using a high-throughput method (tissue microarray) coupled with cutting-edge in situ techniques in a large cohort of patients who had undergone uniform adjuvant chemotherapy. Expression of CD98 heavy chain (CD98HC) and low-level expression of the insulin-like growth factor 2 receptor/mannose-6-phosphate receptor (IGF2R/M6PR) correlated with poor patient prognosis in the whole cohort. Expression of bradykinin receptor B1 (BDKRB1) and testis enhanced gene transcript (TEGT) correlated with good prognosis in woman with oestrogen receptor (ER)-negative breast tumours. These results indicate that this combined approach of isolating primary tumour cells, generating a library to specifically isolate signal-sequence-containing transcripts, and in situ hybridization on tissue microarrays successfully identified novel prognostic markers (BDKRB1, CD98hc, and TEGT) and potential transmembrane therapeutic targets (CD98hc) in breast cancer.