Explaining variation in cancer survival between 11 jurisdictions in the International Cancer Benchmarking Partnership: a primary care vignette survey

OBJECTIVES: The International Cancer Benchmarking Partnership (ICBP) is a collaboration between 6 countries and 12 jurisdictions with similar primary care-led health services. This study investigates primary care physician (PCP) behaviour and systems that may contribute to the timeliness of investigating for cancer and subsequently, international survival differences.

DESIGN: A validated survey administered to PCPs via the internet set out in two parts: direct questions on primary care structure and practice relating to cancer diagnosis, and clinical vignettes, assessing management of scenarios relating to the diagnosis of lung, colorectal or ovarian cancer.

PARTICIPANTS: 2795 PCPs in 11 jurisdictions: New South Wales and Victoria (Australia), British Columbia, Manitoba, Ontario (Canada), England, Northern Ireland, Wales (UK), Denmark, Norway and Sweden.

PRIMARY AND SECONDARY OUTCOME MEASURES: Analysis compared the cumulative proportion of PCPs in each jurisdiction opting to investigate or refer at each phase for each vignette with 1-year survival, and conditional 5-year survival rates for the relevant cancer and jurisdiction. Logistic regression was used to explore whether PCP characteristics or system differences in each jurisdiction affected the readiness to investigate.

RESULTS: 4 of 5 vignettes showed a statistically significant correlation (p<0.05 or better) between readiness to investigate or refer to secondary care at the first phase of each vignette and cancer survival rates for that jurisdiction. No consistent associations were found between readiness to investigate and selected PCP demographics, practice or health system variables.

CONCLUSIONS: We demonstrate a correlation between the readiness of PCPs to investigate symptoms indicative of cancer and cancer survival rates, one of the first possible explanations for the variation in cancer survival between ICBP countries. No specific health system features consistently explained these findings. Some jurisdictions may consider lowering thresholds for PCPs to investigate for cancer-either directly, or by specialist referral, to improve outcomes.

Sorting out mix-ups. The provenance of tissue sections may be confirmed by PCR using microsatellite markers

Standard identification systems usually ensure that biopsy material is correctly associated with a given patient. Sometimes, as when a tumor is unexpectedly found, the provenance (proof of origin) of a tissue sample may be questioned; the tissue may have been mislabelled or contaminated with tissue from another patient. Techniques used to confirm tissue provenance include comparing either tissue markers of gender or ABO blood groups; however, these methods have weak confirmatory power. Recently, the use of DNA-based polymerase chain reaction (PCR) techniques has been reported. Paired, formalin-fixed, paraffin-embedded, 10 microns tissue sections were selected from 17 patients, 8 of whom had carcinoma, either by dividing a biopsy section, using sequential biopsies, or sequential biopsy and autopsy tissue. The resulting 36 samples were coded before analysis. In two additional cases, 1-mm fragments of tumor from one patient were included in the tissue block of benign tissue from another patient, the tumor fragments were identified on hematoxylin-and-eosin-stained sections, separately scraped off the glass slide, and analyzed. Tissue from two clinical cases, one of suspected mislabelling and one with a suspected carry-over of malignant tissue were also investigated. Short tandem repeat sequences (STR) or microsatellites, are 2-5 base pair repeats that vary in their repeat number between individuals. This variation (polymorphism) can be assessed using a PCR. A panel of markers of 3 STRs; ACPP, INT 2, and CYP 19 (on chromosomes 3, 11, and 15, respectively) were used. DNA was isolated from the samples after xylene deparaffinization and proteinase digestion, and was then amplified in a radioactive PCR using primers selected to give a product size ranging from 136-178 bases. Amplified products were electrophoresed on denaturing polyacrylamide gels, dried, and autoradiographed. DNA segments were successfully extracted from all samples but one, which was fixed in Bouin's fluid. By comparing allele sizes from the panel, all tissue pairs (other than the Bouin's pair) were successfully matched, the 1-mm tumor fragments were correctly assigned, and the two clinical problems were solved. STRs are highly informative and robust markers, well suited to PCR of small portions of tissue sections, and are an effective method to confirm the provenance of benign and malignant biopsy and autopsy material.

Neural Network Based Attack on a Masked Implementation of AES

Masked implementations of cryptographic algorithms are often used in commercial embedded cryptographic devices to increase their resistance to side channel attacks. In this work we show how neural networks can be used to both identify the mask value, and to subsequently identify the secret key value with a single attack trace with high probability. We propose the use of a pre-processing step using principal component analysis (PCA) to significantly increase the success of the attack. We have developed a classifier that can correctly identify the mask for each trace, hence removing the security provided by that mask and reducing the attack to being equivalent to an attack against an unprotected implementation. The attack is performed on the freely available differential power analysis (DPA) contest data set to allow our work to be easily reproducible. We show that neural networks allow for a robust and efficient classification in the context of side-channel attacks.

4.11(EC) Report new instrumentation and field measuring technology for tidal currents

One of the challenges the tidal power industry faces, is the requirement of cost effective, reliable but highly accurate acquisition of flow data. Different methods are required , applications range over different spatial and temporal scales. This report assembles in the first sections, theoretical background information on acoustic Doppler Velocimetry and RADAR measurements. The use of existing expertise in field tests of marine vehicles is discussed next, followed by a discussion of issues relating to recreating field conditions in laboratory environments. The last three sections present practical applications of various methods performed in field conditions. While progress has been made over the last years, this overview highlights the challenges in full scale field measurements and knowledge gaps in the industry.

Interleukin-8 and its receptor CXCR2 in the tumour microenvironment promote colon cancer growth, progression and metastasis

BACKGROUND: Colorectal cancer (CRC) is a leading cause of death in the United States. Increased level of interleukin-8 (IL-8) and CXCR2 on tumours and in the tumour microenvironment has been associated with CRC growth, progression and recurrence in patients. Here, we aimed to evaluate the effects of tissue microenvironment-encoded IL-8 and CXCR2 on colon cancer progression and metastasis.

METHODS: A novel immunodeficient, skin-specific IL-8-expressing transgenic model was generated to evaluate colon cancer growth and metastasis. Syngeneic mouse colon cancer cells were grafted in CXCR2 knockout (KO) mice to study the contribution of CXCR2 in the microenvironment to cancer growth.

RESULTS: Elevated levels of IL-8 in the serum and tumour microenvironment profoundly enhanced the growth of human and mouse colon cancer cells with increased peri-tumoural angiogenesis, and also promoted the extravasation of the cancer cells into the lung and liver. The tumour growth was inhibited in CXCR2 KO mice with significantly reduced tumour angiogenesis and increased tumour necrosis.

CONCLUSION: Increased expression of IL-8 in the tumour microenvironment enhanced colon cancer growth and metastasis. Moreover, the absence of its receptor CXCR2 in the tumour microenvironment prevented colon cancer cell growth. Together, our study demonstrates the critical roles of the tumour microenvironment-encoded IL-8/CXCR2 in colon cancer pathogenesis, validating the pathway as an important therapeutic target.

STRIBOB: Authenticated Encryption from GOST R 34.11-2012 LPS Permutation.

Authenticated encryption algorithms protect both the confidentiality and integrity of messages in a single processing pass. We show how to utilize the L◦P ◦S transform of the Russian GOST R 34.11-2012 standard hash “Streebog” to build an efficient, lightweight algorithm for Authenticated Encryption with Associated Data (AEAD) via the Sponge construction. The proposed algorithm “StriBob” has attractive security properties, is faster than the Streebog hash alone, twice as fast as the GOST 28147-89 encryption algorithm, and requires only a modest amount of running-time memory. StriBob is a Round 1 candidate in the CAESAR competition.

Serum- and HDL3-serum amyloid A and HDL3-LCAT activity are influenced by increased CVD-burden

BACKGROUND: High density lipoproteins (HDL) protect against cardiovascular disease (CVD). However, increased serum amyloid-A (SAA) related inflammation may negate this property. This study investigated if SAA was related to CVD-burden.

METHODS: Subjects referred to the rapid chest pain clinic (n = 240) had atherosclerotic burden assessed by cardiac computerised tomography angiography. Subjects were classified as: no-CVD (n = 106), non-obstructive-CVD, stenosis<50% (n = 58) or moderate/significant-CVD, stenosis ≥50% (n = 76). HDL was subfractionated into HDL2 and HDL3 by rapid-ultracentrifugation. SAA-concentration was measured by ELISA and lecithin cholesterol acyltransferase (LCAT) activity measured by a fluorimetric assay.

RESULTS: We illustrated that serum-SAA and HDL3-SAA-concentration were higher and HDL3-LCAT-activity lower in the moderate/significant-CVD-group, compared to the no-CVD and non-obstructive-CVD-groups (percent differences: serum-SAA, +33% & +30%: HDL3-SAA, +65% and +39%: HDL3-LCAT, -6% & -3%; p < 0.05 for all comparisons). We also identified a positive correlation between serum-SAA and HDL3-SAA (r = 0.698; p < 0.001) and a negative correlation between HDL3-SAA and HDL3-LCAT-activity (r = -0.295; p = 0.003), while CVD-burden positively correlated with serum-SAA (r = 0.150; p < 0.05) and HDL3-SAA (r = 0.252; p < 0.001) and negatively correlated with HDL3-LCAT-activity (r = -0.182; p = 0.006). Additionally, multivariate regression analysis adjusted for age, gender, CRP and serum-SAA illustrated that HDL3-SAA was significantly associated with modifying CVD-risk of moderate/significant CVD-risk (p < 0.05).

CONCLUSION: This study has demonstrated increased SAA-related inflammation in subjects with moderate/significant CVD-burden, which appeared to impact on the antiatherogenic potential of HDL. We suggest that SAA may be a useful biomarker to illustrate increased CVD-burden, although this requires further investigation.

Potential public health impact of Age-Related Eye Disease Study results: AREDS report no. 11.

OBJECTIVE:

To estimate the potential public health impact of the findings of the Age-Related Eye Disease Study (AREDS) on reducing the number of persons developing advanced age-related macular degeneration (AMD) during the next 5 years in the United States.

METHODS:

The AREDS clinical trial provides estimates of AMD progression rates and of reduction in risk of developing advanced AMD when a high-dose nutritional supplement of antioxidants and zinc is used. These results are applied to estimates of the US population at risk, to estimate the number of people who would potentially avoid advanced AMD during 5 years if those at risk were to take a supplement such as that used in AREDS.

RESULTS:

An estimated 8 million persons at least 55 years old in the United States have monocular or binocular intermediate AMD or monocular advanced AMD. They are considered to be at high risk for advanced AMD and are those for whom the AREDS formulation should be considered. Of these people, 1.3 million would develop advanced AMD if no treatment were given to reduce their risk. If all of these people at risk received supplements such as those used in AREDS, more than 300,000 (95% confidence interval, 158,000-487,000) of them would avoid advanced AMD and any associated vision loss during the next 5 years.

CONCLUSION:

If people at high risk for advanced AMD received supplements such as those suggested by AREDS results, the potential impact on public health in the United States would be considerable during the next 5 years.

Geologia 11.º ano - guia do professor

Na primeira parte, são fundamentalmente as orientações metodologicas, as quais incluem referências à educação para o desenvolvimento sustentável, algumas sugestões didáticas e observações relativas à avalliação das aprendizagens. Pretende-se que os professores desenvolvam um quadro de referência, o qual será importante para justificar algumas das decisões que terão de tomar na preparação das suas aulas e, depois, em situação de ato de ensino. Na segunda parte, são apresentados para cada uma das quatro Unidades Temáticas que integram o programa de Geologia do 11.º ano, mapas de conceitos, propostas de planificação, sugestões diversas, recursos e recomendações de avaliação. Tudo isto visa proporcionar aos professores elementos que lhes permitam vir a reunir um conjunto de condições necessárias a uma abordagem sustentada e atual do programa, em íntima articulação com o manual, de modo que os alunos procedam a uma aprendizagem que conduza a uma cidadania ativa.