Cost-effectiveness of stereotactic large-core needle biopsy for nonpalpable breast lesions compared to open-breast biopsy

This paper demonstrates that the introduction of large-core needle biopsy (LCNB) replacing needle-localised breast biopsy (NLBB) for nonpalpable (screen-detected) breast lesions could result in substantial cost savings at the expense of a possible slight increase in breast cancer mortality. The cost-effectiveness of LCNB and NLBB was estimated using a microsimulation model. The sensitivity of LCNB (0.97) and resource use and costs of LCNB and NLBB were derived from a multicentre consecutive cohort study among 973 women who consented in getting LCNB and NLBB, if LCNB was negative. Sensitivity analyses were performed. Replacing NLBB with LCNB would result in approximately six more breast cancer deaths per year (in a target population of 2.1 million women), or in 1000 extra life-years lost from breast cancer (effect over 100 years). The total costs of management of breast cancer (3% discounted) are estimated at £4676 million with NLBB; introducing LCNB would save £13 million. The incremental cost-effectiveness ratio of continued NLBB vs LCNB would be £12 482 per additional life-year gained (3% discounted); incremental costs range from £-21 687 (low threshold for breast biopsy) to £74 378 (high sensitivity of LCNB)

Polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls in fish from the Netherlands: concentrations, profiles and comparison with DR CALUX® bioassay results

Fish from Dutch markets were analysed for concentrations of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) and compared with the new European maximum residue levels (MRLs), set in 2006. In a first study on 11 different fish and shellfish from various locations, concentrations of PCDD/Fs were nearly all below the MRL for PCDD/Fs [4 pg toxic equivalents (TEQ) per gram wet weight (ww)] and nearly all below 8 pg total TEQ/g ww, the new MRL for the sum of PCDD/Fs and DL-PCBs. Some samples exceeded the total TEQ MRL, such as anchovy, tuna and sea bass. Furthermore, 20 (out of 39) wild eel samples exceeded the specific MRL for eel (12 pg total TEQ/g ww), as the study revealed PCDD/F TEQ levels of 0.2-7.9 pg TEQ/g ww and total TEQ values of 0.9 to 52 pg/g ww. TEQ levels in farmed and imported eel were lower and complied with the MRLs. Smoking eel, a popular tradition in the Netherlands, only had marginal effects on PCDD/F and DL-PCB concentrations. Owing to volatilization, concentrations of lower-chlorinated PCBs were reduced to below the limit of quantification after smoking. DL-PCBs contributed 61-97% to the total TEQ in all eel samples. This also holds for other fish and shellfish (except shrimps): DL-PCB contributed (on average) from 53 (herring) to 83% (tuna) to the total TEQ. Principal-component analysis revealed distinctive congener profiles for PCDD/Fs and non-ortho PCBs for mussels, pikeperch, herring and various Mediterranean fish. The application of new TCDD toxic equivalency factors (TEFs) set by the World Health Organization in 2006 (to replace the 1997 TEFs) resulted in lower TEQ values, mainly owing to a decreased mono-ortho PCB contribution. This decrease is most pronounced for eel, owing to the relative high mono-ortho PCB concentrations in eel. Consequently, a larger number of samples would comply with the MRLs when the new TEFs are applied. The DR CALUX (R) assay may be used for screening total TEQ levels in eel, in combination with gas chromatography-high resolution mass spectrometry confirmation of suspected samples. An almost 1:1 correlation was found when the 1997 TEFs were applied, but, surprisingly, a 1.4-fold overestimation occurred with application of the 2006 TEFs

Smoking, alcohol consumption, physical activity, and family history and the risks of acute myocardial infarction and unstable angina pectoris: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Few studies investigated the association between smoking, alcohol consumption, or physical activity and the risk of unstable angina pectoris (UAP), while the strength of these associations may differ compared to other coronary diseases such as acute myocardial infarction (AMI). Therefore, we investigated whether the associations of these lifestyle factors with UAP differed from those with AMI. Additionally, we investigated whether these effects differed between subjects with and without a family history of myocardial infarction (MI).</p> <p>Methods</p> <p>The CAREMA study consists of 21,148 persons, aged 20-59 years at baseline and randomly sampled from the Maastricht region in 1987-1997. At baseline, all participants completed a self-administered questionnaire. After follow-up of maximally 16.9 years, 420 AMI and 274 UAP incident cases were registered. Incidence rate ratios (RRs) were estimated using Cox proportional hazards models.</p> <p>Results</p> <p>For both diseases, smoking increased the risk while alcohol consumption was associated with a protective effect. Associations with both risk factors were stronger for AMI than UAP, although this difference was only statistically significant for smoking. In men, an inverse association was found with physical activity during leisure time which seemed to be stronger for the risk of UAP than of AMI. On the contrary, physical activity during leisure time was associated with an increased risk of both AMI and UAP in women which seemed to be weaker for UAP than for AMI. Except for occupational physical activity in women, no significant interactions on a multiplicative scale were found between the lifestyle factors and family history of MI. Nevertheless, the highest risks were found in subjects with both a positive family history and the most unfavorable level of the lifestyle factors.</p> <p>Conclusions</p> <p>The strength of the associations with the lifestyle factors did not differ between AMI and UAP, except for smoking. Furthermore, the effects of the lifestyle factors on the risk of both coronary diseases were similar for subjects with and without a positive family history.</p

Results from the national sepsis practice survey: predictions about mortality and morbidity and recommendations for limitation of care orders

Introduction: Critically ill patients and families rely upon physicians to provide estimates of prognosis and recommendations for care. Little is known about patient and clinician factors which influence these predictions. The association between these predictions and recommendations for continued aggressive care is also understudied. Methods: We administered a mail-based survey with simulated clinical vignettes to a random sample of the Critical Care Assembly of the American Thoracic Society. Vignettes represented a patient with septic shock with multi-organ failure with identical APACHE II scores and sepsis-associated organ failures. Vignettes varied by age (50 or 70 years old), body mass index (BMI) (normal or obese) and co-morbidities (none or recently diagnosed stage IIA lung cancer). All subjects received the vignettes with the highest and lowest mortality predictions from pilot testing and two additional, randomly selected vignettes. Respondents estimated outcomes and selected care for each hypothetical patient. Results: Despite identical severity of illness, the range of estimates for hospital mortality (5th to 95th percentile range, 17% to 78%) and for problems with self-care (5th to 95th percentile range, 2% to 74%) was wide. Similar variation was observed when clinical factors (age, BMI, and co-morbidities) were identical. Estimates of hospital mortality and problems with self-care among survivors were significantly higher in vignettes with obese BMIs (4.3% and 5.3% higher, respectively), older age (8.2% and 11.6% higher, respectively), and cancer diagnosis (5.9% and 6.9% higher, respectively). Higher estimates of mortality (adjusted odds ratio 1.29 per 10% increase in predicted mortality), perceived problems with self-care (adjusted odds ratio 1.26 per 10% increase in predicted problems with self-care), and early-stage lung cancer (adjusted odds ratio 5.82) were independently associated with recommendations to limit care. Conclusions: The studied clinical factors were consistently associated with poorer outcome predictions but did not explain the variation in prognoses offered by experienced physicians. These observations raise concern that provided information and the resulting decisions about continued aggressive care may be influenced by individual physician perception. To provide more reliable and accurate estimates of outcomes, tools are needed which incorporate patient characteristics and preferences with physician predictions and practices

Expression of Trichoderma reesei cellulases CBHI and EGI in Ashbya gossypii

To explore the potential of Ashbya gossypii as a host for the expression of recombinant proteins and to assess whether protein secretion would be more similar to the closely related Saccharomyces cerevisiae or to other filamentous fungi, endoglucanase I (EGI) and cellobiohydrolase I (CBHI) from the fungus Trichoderma reesei were successfully expressed in A. gossypii from plasmids containing the two micron sequences from S. cerevisiae, under the S. cerevisiae PGK1 promoter. The native signal sequences of EGI and CBHI were able to direct the secretion of EGI and CBHI into the culture medium in A. gossypii. Although CBHI activity was not detected using 4- methylumbelliferyl-β-D-lactoside as substrate, the protein was detected by Western blot using monoclonal antibodies. EGI activity was detectable, the specific activity being comparable to that produced by a similar EGI producing S. cerevisiae construct. More EGI was secreted than CBHI, or more active protein was produced. Partial characterization of CBHI and EGI expressed in A. gossypii revealed overglycosylation when compared with the native T. reesei proteins, but the glycosylation was less extensive than on cellulases expressed in S. cerevisiae.Fundação para a Ciência e a Tecnologia (FCT

Genetic Variation in Jasmonic Acid- and Spider Mite-Induced Plant Volatile Emission of Cucumber Accessions and Attraction of the Predator Phytoseiulus persimilis

Cucumber plants (Cucumis sativus L.) respond to spider–mite (Tetranychus urticae) damage with the release of specific volatiles that are exploited by predatory mites, the natural enemies of the spider mites, to locate their prey. The production of volatiles also can be induced by exposing plants to the plant hormone jasmonic acid. We analyzed volatile emissions from 15 cucumber accessions upon herbivory by spider mites and upon exposure to jasmonic acid using gas chromatography—mass spectrometry. Upon induction, cucumber plants emitted over 24 different compounds, and the blend of induced volatiles consisted predominantly of terpenoids. The total amount of volatiles was higher in plants treated with jasmonic acid than in those infested with spider mites, with (E)-4,8-dimethyl-1,3,7-nonatriene, (E,E)-α-farnesene, and (E)-β-ocimene as the most abundant compounds in all accessions in both treatments. Significant variation among the accessions was found for the 24 major volatile compounds. The accessions differed strongly in total amount of volatiles emitted, and displayed very different odor profiles. Principal component analysis performed on the relative quantities of particular compounds within the blend revealed clusters of highly correlated volatiles, which is suggestive of common metabolic pathways. A number of cucumber accessions also were tested for their attractiveness to Phytoseiulus persimilis, a specialist predator of spider mites. Differences in the attraction of predatory mites by the various accessions correlated to differences in the individual chemical profiles of these accessions. The presence of genetic variation in induced plant volatile emission in cucumber shows that it is possible to breed for cucumber varieties that are more attractive to predatory mites and other biological control agents

Search for supersymmetric particles in scenarios with a gravitino LSP and stau NLSP

Sleptons, neutralinos and charginos were searched for in the context of scenarios where the lightest supersymmetric particle is the gravitino. It was assumed that the stau is the next-to-lightest supersymmetric particle. Data collected with the DELPHI detector at a centre-of-mass energy near 189 GeV were analysed combining the methods developed in previous searches at lower energies. No evidence for the production of these supersymmetric particles was found. Hence, limits were derived at 95% confidence level.Comment: 31 pages, 14 figure

Bilateral Sensory Abnormalities in Patients with Unilateral Neuropathic Pain; A Quantitative Sensory Testing (QST) Study

In patients who experience unilateral chronic pain, abnormal sensory perception at the non-painful side has been reported. Contralateral sensory changes in these patients have been given little attention, possibly because they are regarded as clinically irrelevant. Still, bilateral sensory changes in these patients could become clinically relevant if they challenge the correct identification of their sensory dysfunction in terms of hyperalgesia and allodynia. Therefore, we have used the standardized quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain (DFNS) to investigate somatosensory function at the painful side and the corresponding non-painful side in unilateral neuropathic pain patients using gender- and age-matched healthy volunteers as a reference cohort. Sensory abnormalities were observed across all QST parameters at the painful side, but also, to a lesser extent, at the contralateral, non-painful side. Similar relative distributions regarding sensory loss/gain for non-nociceptive and nociceptive stimuli were found for both sides. Once a sensory abnormality for a QST parameter at the affected side was observed, the prevalence of an abnormality for the same parameter at the non-affected side was as high as 57% (for Pressure Pain Threshold). Our results show that bilateral sensory dysfunction in patients with unilateral neuropathic pain is more rule than exception. Therefore, this phenomenon should be taken into account for appropriate diagnostic evaluation in clinical practice. This is particularly true for mechanical stimuli where the 95% Confidence Interval for the prevalence of sensory abnormalities at the non-painful side ranges between 33% and 50%

The Leukemia-Specific Fusion Gene ETV6/RUNX1 Perturbs Distinct Key Biological Functions Primarily by Gene Repression

-positive leukemic cell lines.-positive ALL samples underline the relevance of these pathways and molecular functions. We also validated six differentially expressed genes representing the categories “stem cell properties”, “B-cell differentiation”, “immune response”, “cell adhesion” and “DNA damage” with RT-qPCR. fusion gene interferes with key regulatory functions that shape the biology of this leukemia subtype. E/R may thus indeed constitute the essential driving force for the propagation and maintenance of the leukemic process irrespective of potential consequences of associated secondary changes. Finally, these findings may also provide a valuable source of potentially attractive therapeutic targets

Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation.

BACKGROUND: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD. METHODS: Fifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. RESULTS: We identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci (TTN, CAND2, SCN10A, PITX2, CAV1, SYNPO2L, SOX5, TBX5, MYH6, RPL3L). The top variants at known sarcomere genes (TTN, MYH6) were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, PITX2 and SCN10A) were associated with longer PWD but lower AF risk. CONCLUSIONS: Our results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF