Global proteomic characterization of microdissected estrogen receptor positive breast tumors

We here describe two proteomic datasets deposited in ProteomeXchange via PRIDE partner repository [1] with dataset identifiers PXD000484 (defined as "training") and PXD000485 (defined as "test") that have been used for the development of a tamoxifen outcome predictive signature [2]. Both datasets comprised 56 fresh frozen estrogen receptor (ER) positive primary breast tumor specimens derived from patients who received tamoxifen as first line therapy for recurrent disease. Patient groups were defined based on time to progression (TTP) after start of tamoxifen therapy (6 months cutoff): 32 good and 24 poor treatment outcome patients were comprised in the training set, respectively. The test set included 41 good and 15 poor treatment outcome patients. All specimens were subjected to laser capture microdissection (LCM) to enrich for epithelial tumor cells prior to high resolution mass spectrometric (MS) analysis. Protein identificat

Modelling Clock Synchronization in the Chess gMAC WSN Protocol

We present a detailled timed automata model of the clock synchronization algorithm that is currently being used in a wireless sensor network (WSN) that has been developed by the Dutch company Chess. Using the Uppaal model checker, we establish that in certain cases a static, fully synchronized network may eventually become unsynchronized if the current algorithm is used, even in a setting with infinitesimal clock drifts

UbiqLog: a generic mobile phone based life-log framework

Smart phones are conquering the mobile phone market; they are not just phones they also act as media players, gaming consoles, personal calendars, storage, etc. They are portable computers with fewer computing capabilities than personal computers. However unlike personal computers users can carry their smartphone with them at all times. The ubiquity of mobile phones and their computing capabilities provide an opportunity of using them as a life logging device. Life-logs (personal e-memories) are used to record users' daily life events and assist them in memory augmentation. In a more technical sense, life-logs sense and store users' contextual information from their environment through sensors, which are core components of life-logs. Spatio-temporal aggregation of sensor information can be mapped to users' life events. We propose UbiqLog, a lightweight, configurable and extendable life-log framework that uses mobile phone as a device for life logging. The proposed framework extends previous research in this field, which investigated mobile phones as life-log tool through continuous sensing. Its openness in terms of sensor configuration allows developers to create exible, multipurpose life-log tools. In addition to that this framework contains a data model and an architecture, which can be used as reference model for further life-log development, including its extension to other devices, such as ebook readers, T.V.s, etc

Position Paper: Secure Infrastructure for Scientific Data Life Cycle Management

Abstract—Within the Austrian Grid project phase 2, three different groups, each allocated to a different workpackage, join their efforts to implement a grid infrastructure for the european research project “Breath Gas Analysis for molecular oriented diseases”. This position paper provides background on the task and the resulting requirements, a presentation on solutions developed during related projects in the application domain, identifies problems that have not yet been solved, and finally presents the intended solution to be developed. I. INTRODUCTION & CONTEXT This position paper describes the current state, the in-tended realisation and a discussion of the project Grid Breath Gas Analysis (BAMOD-Grid) carried out withi

First-Trimester Follistatin-Like-3 Levels in Pregnancies Complicated by Subsequent Gestational Diabetes Mellitus

Objective: To determine whether maternal levels of follistatin-like-3 (FSTL3), an inhibitor of activin and myostatin involved in glucose homeostasis, are altered in the first trimester of pregnancies complicated by subsequent gestational diabetes mellitus (GDM). Research Design and Methods: This was a nested case-control study of subjects enrolled in a prospective cohort of pregnant women with and without GDM ($\geq$2 abnormal values on a 100-g glucose tolerance test at ~28 weeks of gestation). We measured FSTL3 levels in serum collected during the first trimester of pregnancy. Logistic regression analyses were used to determine the risk of GDM. Results: Women who developed GDM (n = 37) had lower first-trimester serum levels of FSTL3 compared with women who did not (n = 127) (median 10,789 [interquartile range 7,013-18,939] vs. 30,670 [18,370-55,484] pg/ml, P < 0.001). When subjects were divided into tertiles based on FSTL3 levels, women with the lowest levels demonstrated a marked increase in risk for developing GDM in univariate (odds ratio 11.2 [95% CI 3.6-35.3]) and multivariate (14.0 [4.1-47.9]) analyses. There was a significant negative correlation between first-trimester FSTL3 levels and ~28-week nonfasting glucose levels (r = -0.30, P < 0.001). Conclusions: First-trimester FSTL3 levels are associated with glucose intolerance and GDM later in pregnancy

Meeting human resources for health staffing goals by 2018: a quantitative analysis of policy options in Zambia

<p>Abstract</p> <p>Background</p> <p>The Ministry of Health (MOH) in Zambia is currently operating with fewer than half of the health workers required to deliver basic health services. The MOH has developed a human resources for health (HRH) strategic plan to address the crisis through improved training, hiring, and retention. However, the projected success of each strategy or combination of strategies is unclear.</p> <p>Methods</p> <p>We developed a model to forecast the size of the public sector health workforce in Zambia over the next ten years to identify a combination of interventions that would expand the workforce to meet staffing targets. The key forecasting variables are training enrolment, graduation rates, public sector entry rates for graduates, and attrition of workforce staff. We model, using Excel (Office, Microsoft; 2007), the effects of changes in these variables on the projected number of doctors, clinical officers, nurses and midwives in the public sector workforce in 2018.</p> <p>Results</p> <p>With no changes to current training, hiring, and attrition conditions, the total number of doctors, clinical officers, nurses, and midwives will increase from 44% to 59% of the minimum necessary staff by 2018. No combination of changes in staff retention, graduation rates, and public sector entry rates of graduates by 2010, without including training expansion, is sufficient to meet staffing targets by 2018 for any cadre except midwives. Training enrolment needs to increase by a factor of between three and thirteen for doctors, three and four for clinical officers, two and three for nurses, and one and two for midwives by 2010 to reach staffing targets by 2018. Necessary enrolment increases can be held to a minimum if the rates of retention, graduation, and public sector entry increase to 100% by 2010, but will need to increase if these rates remain at 2008 levels.</p> <p>Conclusions</p> <p>Meeting the minimum need for health workers in Zambia this decade will require an increase in health training school enrolment. Supplemental interventions targeting attrition, graduation and public sector entry rates can help close the gap. HRH modelling can help MOH policy makers determine the relative priority and level of investment needed to expand Zambia's workforce to target staffing levels.</p

4-protein signature predicting tamoxifen treatment outcome in recurrent breast cancer

Estrogen receptor (ER) positive tumors represent the majority of breast malignancies, and are effectively treated with hormonal therapies, such as tamoxifen. However, in the recurrent disease resistance to tamoxifen therapy is common and a major cause of death. In recent years, in-depth proteome analyses have enabled identification of clinically useful biomarkers, particularly, when heterogeneity in complex tumor tissue was reduced using laser capture microdissection (LCM). In the current study, we performed high resolution proteomic analysis on two cohorts of ER positive breast tumors derived from patients who either manifested good or poor outcome to tamoxifen treatment upon recurrence. A total of 112 fresh frozen tumors were collected from multiple medical centers and divided into two sets: an in-house training and a multi-center test set. Epithelial tumor cells were enriched with LCM and analyzed by nano-LC Orbitrap mass spectrometry (MS), which yielded >3000 and >4000 quantified proteins in the training and test sets, respectively. Raw data are available via ProteomeXchange with identifiers PXD000484 and PXD000485. Statistical analysis showed differential abundance of 99 proteins, of which a subset of 4 proteins was selected through a multivariate step-down to develop a predictor for tamoxifen treatment outcome. The 4-protein signature significantly predicted poor outcome patients in the test set, independent of predictive histopathological characteristics (hazard ratio [HR] = 2.17; 95% confidence interval [CI] = 1.15 to 4.17; multivariate Cox regression p value = 0.017). Immunohistochemical (IHC) staining of PDCD4, one of the signature proteins, on an independent set of formalin-fixed paraffin-embedded tumor tissues provided and independent technical validation (HR = 0.72; 95% CI = 0.57 to 0.92; multivariate Cox regression p value = 0.009). We hereby report the first validated protein predictor for tamoxifen treatment outcome in recurrent ER-positive breast cancer. IHC further showed that PDCD4 is an independent marker

The human resource for health situation in Zambia: deficit and maldistribution

<p>Abstract</p> <p>Introduction</p> <p>Current health policy directions in Zambia are formulated in the National Health Strategic Plan. The Plan focuses on national health priorities, which include the human resources (HR) crisis. In this paper we describe the way the HRH establishment is distributed in the different provinces of Zambia, with a view to assess the dimension of shortages and of imbalances in the distribution of health workers by province and by level of care.</p> <p>Population and methods</p> <p>We used secondary data from the "March 2008 payroll data base", which lists all the public servants on the payroll of the Ministry of Health and of the National Health Service facilities. We computed rates and ratios and compared them.</p> <p>Results</p> <p>The highest relative concentration of all categories of workers was observed in Northern, Eastern, Lusaka, Western and Luapula provinces (in decreasing order of number of health workers).</p> <p>The ratio of clinical officers (mid-level clinical practitioners) to general medical officer (doctors with university training) varied from 3.77 in the Lusaka to 19.33 in the Northwestern provinces. For registered nurses (3 to 4 years of mid-level training), the ratio went from 3.54 in the Western to 15.00 in Eastern provinces and for enrolled nurses (two years of basic training) from 4.91 in the Luapula to 36.18 in the Southern provinces.</p> <p>This unequal distribution was reflected in the ratio of population per cadre. The provincial distribution of personnel showed a skewed staff distribution in favour of urbanized provinces, e.g. in Lusaka's doctor: population ratio was 1: 6,247 compared to Northern Province's ratio of 1: 65,763.</p> <p>In the whole country, the data set showed only 109 staff in health posts: 1 clinical officer, 3 environmental health technologists, 2 registered nurses, 12 enrolled midwives, 32 enrolled nurses, and 59 other.</p> <p>The vacancy rates for level 3 facilities(central hospitals, national level) varied from 5% in Lusaka to 38% in Copperbelt Province; for level 2 facilities (provincial level hospitals), from 30% for Western to 70% for Copperbelt Province; for level 1 facilities (district level hospitals), from 54% for the Southern to 80% for the Western provinces; for rural health centres, vacancies varied from 15% to 63% (for Lusaka and Luapula provinces respectively); for urban health centres the observed vacancy rates varied from 13% for the Lusaka to 96% for the Western provinces. We observed significant shortages in most staff categories, except for support staff, which had a significant surplus.</p> <p>Discussion and Conclusions</p> <p>This case study documents how a peaceful, politically stable African country with a longstanding tradition of strategic management of the health sector and with a track record of innovative approaches dealt with its HRH problems, but still remains with a major absolute and relative shortage of health workers. The case of Zambia reinforces the idea that training more staff is necessary to address the human resources crisis, but it is not sufficient and has to be completed with measures to mitigate attrition and to increase productivity.</p