In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography

Background and aims: Positron emission tomography (PET) using 18F labelled 2-fluoro-2-deoxy-D-glucose (18FDG) is an established imaging tool, although the recent development of a biologically stable thymidine analogue [18F] 3'-deoxy-3-fluorothymidine (18FLT) has allowed PET to image cellular proliferation by utilising the salvage pathway of DNA synthesis. In this study, we have compared uptake of 18FLT and 18FDG with MIB-1 immunohistochemistry to evaluate the role of PET in quantifying in vivo cellular proliferation in colorectal cancer (CRC). Patients and methods: Patients with resectable, primary, or recurrent CRC were prospectively studied. Thirteen lesions from 10 patients (five males, five females), median age 68 years (range 54–87), were evaluated. Patients underwent 18FDG and 18FLT PET scanning. Tracer uptake within lesions was quantified using standardised uptake values (SUVs). Histopathological examination and MIB-1 immunohistochemistry were performed on all lesions, and proliferation quantified by calculating a labelling index (% of MIB-1 positively stained nuclei within 1500 tumour cells). Results: Histology confirmed adenocarcinoma in 12 of 13 lesions; the remaining lesion was reactive. All eight extrahepatic lesions were visualised using both 18FLT and 18FDG. Three of the five resected liver metastases were also avid for 18FLT and showed high proliferation, while the remaining two lesions which demonstrated no uptake of 18FLT had correspondingly very low proliferation. There was a statistically significant positive correlation (r =0.8, p<0.01) between SUVs of the tumours visualised with 18FLT and the corresponding MIB-1 labelling indices. No such correlation was demonstrated with 18FDG avid lesions (r =0.4). Conclusions: 18FLT PET correlates with cellular proliferation markers in both primary and metastatic CRC. This technique could provide a mechanism for in vivo grading of malignancy and early prediction of response to adjuvant chemotherapy

Gradient-based optimization techniques for the design of static controllers for Markov jump linear systems with unobservable modes

The paper formulates the static control problem of Markov jump linear systems, assuming that the controller does not have access to the jump variable. We derive the expression of the gradient for the cost motivated by the evaluation of 10 gradient-based optimization techniques. The numerical efficiency of these techniques is verified by using the data obtained from practical experiments. The corresponding solution is used to design a scheme to control the velocity of a real-time DC motor device subject to abrupt power failures

Modeling and simulation of tankless gas water heaters to reduce temperature overshoots and undershoots

The hot water user’s comfort perception is severely affected by sudden water temperature changes above a certain magnitude. Sudden temperature changes, with overshoots or undershoots, could occur in hot water systems based on domestic tankless gas water heaters (TGWH). These are mainly due to sudden changes on the overall hot water flow rate demand and to the response delays inherent to the heating system, which cannot be anticipated by the equipment controller. This work presents the modeling and simulation of a proposed solution to reduce the temperature undershoots or overshoots to small acceptable values, not perceptible by the users. The proposed solution includes a tank acting as a thermal capacitance, a mixing valve to mix the tank and heat cell water flows and a bypass valve, connected to the output, the latter to eliminate the outlet temperature overshoots. Typical situations originating temperature undershoots and/or overshoots are simulated for validation of the proposed solution, showing that it is able to: a) Substantially reduce the waiting time for hot water in the cold start of the water heater; b) Respond to sudden increases of the hot water flow with only a small acceptable decrease in the outlet water temperature (for hot water flow rates varying from 2 to 14 L/min the temperature undershoots are lower than 0.5 °C); and c) Complete elimination of temperature overshoots for sudden decreases of the hot water flow rate.Papers presented to the 12th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Costa de Sol, Spain on 11-13 July 2016

Fontes De Obtenção De Medicamentos Para Hipertensão E Diabetes No Brasil: Resultados De Inquérito Telefônico Nas Capitais Brasileiras E No Distrito Federal, 2011

This study aimed to analyze differences between patients with diabetes and hypertension in drug treatment and their sources for obtaining medication. This was a cross-sectional study with data from the VIGITEL telephone survey in 2011 in Brazil’s state capitals and Federal District. Some 72% of the 15,027 hypertensive patients and 78.2% of the 4,083 diabetics were on medication; 45.8% of the hypertensive patients obtained their medications from public health units, 15.9% from the Popular Pharmacy program, and 38.3% from drugstores, pharmacies, and other sources. The rates among diabetics were 54.4%, 16.2%, and 29.4%, respectively. In the public health units the percentages were highest among individuals with less schooling, black or brown skin, and without private health plans, while the percentages in the Popular Pharmacy program and drugstores/pharmacies and other sources were higher among individuals with more schooling, white skin, and private health plans. Access to different sources of medicines showed disparities between Brazil’s regions and state capitals and between social segments of the population. © 2016, Fundacao Oswaldo Cruz. All rights reserved.32

Subclinical thyroid dysfunction and the risk for fractures: a systematic review and meta-analysis.

BACKGROUND: Data on the association between subclinical thyroid dysfunction and fractures conflict. PURPOSE: To assess the risk for hip and nonspine fractures associated with subclinical thyroid dysfunction among prospective cohorts. DATA SOURCES: Search of MEDLINE and EMBASE (1946 to 16 March 2014) and reference lists of retrieved articles without language restriction. STUDY SELECTION: Two physicians screened and identified prospective cohorts that measured thyroid function and followed participants to assess fracture outcomes. DATA EXTRACTION: One reviewer extracted data using a standardized protocol, and another verified data. Both reviewers independently assessed methodological quality of the studies. DATA SYNTHESIS: The 7 population-based cohorts of heterogeneous quality included 50,245 participants with 1966 hip and 3281 nonspine fractures. In random-effects models that included the 5 higher-quality studies, the pooled adjusted hazard ratios (HRs) of participants with subclinical hyperthyroidism versus euthyrodism were 1.38 (95% CI, 0.92 to 2.07) for hip fractures and 1.20 (CI, 0.83 to 1.72) for nonspine fractures without statistical heterogeneity (P = 0.82 and 0.52, respectively; I2= 0%). Pooled estimates for the 7 cohorts were 1.26 (CI, 0.96 to 1.65) for hip fractures and 1.16 (CI, 0.95 to 1.42) for nonspine fractures. When thyroxine recipients were excluded, the HRs for participants with subclinical hyperthyroidism were 2.16 (CI, 0.87 to 5.37) for hip fractures and 1.43 (CI, 0.73 to 2.78) for nonspine fractures. For participants with subclinical hypothyroidism, HRs from higher-quality studies were 1.12 (CI, 0.83 to 1.51) for hip fractures and 1.04 (CI, 0.76 to 1.42) for nonspine fractures (P for heterogeneity = 0.69 and 0.88, respectively; I2 = 0%). LIMITATIONS: Selective reporting cannot be excluded. Adjustment for potential common confounders varied and was not adequately done across all studies. CONCLUSION: Subclinical hyperthyroidism might be associated with an increased risk for hip and nonspine fractures, but additional large, high-quality studies are needed. PRIMARY FUNDING SOURCE: Swiss National Science Foundation

Patient and physician gender concordance in preventive care in university primary care settings.

OBJECTIVE: To assess the quality of preventive care according to physician and patient gender in a country with universal health care coverage. METHODS: We assessed a retrospective cohort study of 1001 randomly selected patients aged 50-80years followed over 2years (2005-2006) in 4 Swiss university primary care settings (Basel, Geneva, Lausanne, Zürich). We used indicators derived from RAND's Quality Assessment Tools and examined percentages of recommended preventive care. Results were adjusted using hierarchical multivariate logistic regression models. RESULTS: 1001 patients (44% women) were followed by 189 physicians (52% women). Female patients received less preventive care than male patients (65.2% vs. 72.1%, p&lt;0.001). Female physicians provided significantly more preventive care than male physicians (p=0.01) to both female (66.7% vs. 63.6%) and male patients (73.4% vs. 70.7%). After multivariate adjustment, differences according to physician (p=0.02) and patient gender (p&lt;0.001) remained statistically significant. Female physicians provided more recommended cancer screening than male physicians (78.4 vs. 71.9%, p=0.01). CONCLUSIONS: In Swiss university primary care settings, female patients receive less preventive care than male patients, with female physicians providing more preventive care than male physicians. Greater attention should be paid to female patients in preventive care and to why female physicians tend to provide better preventive care

A uniqueness theorem for degenerate Kerr-Newman black holes

We show that the domains of dependence of stationary, $I^+$-regular, analytic, electrovacuum space-times with a connected, non-empty, rotating, degenerate event horizon arise from Kerr-Newman space-times

Subclinical Thyroid Dysfunction and the Risk of Cognitive Decline: a Meta-Analysis of Prospective Cohort Studies.

Although both overt hyper- and hypothyroidism are known to lead to cognitive impairment, data on the association between subclinical thyroid dysfunction and cognitive function are conflicting. This study sought to determine the risk of dementia and cognitive decline associated with subclinical thyroid dysfunction among prospective cohorts. We searched in MEDLINE and EMBASE from inception until November 2014. Two physicians identified prospective cohorts that assessed thyroid function and cognitive outcomes (dementia; Mini-Mental State Examination [MMSE]). Data were extracted by one reviewer following standardized protocols and verified by a second reviewer. The primary outcome was dementia and decline in cognitive function was the secondary outcome. Eleven prospective cohorts followed 16,805 participants during a median followup of 44.4 months. Five studies analyzed the risk of dementia in subclinical hyperthyroidism (SHyper) (n = 6410), six in subclinical hypothyroidism (SHypo) (n = 7401). Five studies analyzed MMSE decline in SHyper (n = 7895), seven in SHypo (n = 8960). In random-effects models, the pooled adjusted risk ratio for dementia in SHyper was 1.67 (95% confidence interval, 1.04; 2.69) and 1.14 (95% confidence interval, 0.84; 1.55) in SHypo vs euthyroidism, both without evidence of significant heterogeneity (I(2) = 0.0%). The pooled mean MMSE decline from baseline to followup (mean 32 mo) did not significantly differ between SHyper or SHypo vs euthyroidism. SHyper might be associated with an elevated risk for dementia, whereas SHypo is not, and both conditions are not associated with faster decline in MMSE over time. Available data are limited, and additional large, high-quality studies are needed