Reusing IEEE 1687-Compatible Instruments and Sub-Networks over a System Bus

Accessing embedded test and monitoring circuitry (the so-called embedded instruments) in in-field products can reduce maintenance and diagnostics costs. Performing such access can be facilitated when done over an internal system bus, due to that it might be faster and less cumbersome to reach a system processor (on an in-field product) over a network interface, compared with the effort and speed of gaining access to a test interface on the same product. Enabling such access might require that, at the component level, the embedded instruments in a system-on-chip (SoC) become accessible both from a chip interface and from an on-chip processor over a system bus. Although this reuse of embedded instruments can be achieved by already existing standards, such as IEEE 1687, the system bus might become a scalability bottleneck when the number of instruments that are to be reused increases. In this paper, we propose two solutions that address the scalability in this type of reuse while maintaining compatibility with IEEE 1687 tools. We also discuss the trade-offs associated with each approach and present timing analyses that by considering system parameters such as clock rates determine how the correct operation can be guaranteed. To validate the proposed solutions, we have implemented them on an FPGA using AXI as system bus, and have used standard IEEE 1687 tools to access the instruments. We present some details of the implementation to highlight practical issues such as clock domain crossing, as well as how the presented timing analyses can be used to adjust design parameters

Immunohistochemical categorisation of ductal carcinoma in situ of the breast

The aim of this study is to analyse whether immunohistochemistry (IHC) applying a broad set of markers could be used to categorise ductal carcinoma in situ (DCIS) of the breast in distinct subgroups corresponding to the recently defined molecular categories of invasive carcinoma. Immunohistochemistry of pure DCIS cases constructed in tissue arrays was performed with 16 markers (oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), Bcl-2, p53, Her2, insulin-like growth factor receptor, E-cadherin, epithelial membrane antigen (EMA), CA125, keratins 5/6, 14, 19, epidermal growth factor receptor, S100, and CD31). Results in 163 cases were analysed by unsupervised hierarchical clustering. Histological classification was performed by review of whole tissue sections and identified 36 well-, 55 intermediately, and 72 poorly differentiated DCISs. Unsupervised hierarchical cluster analysis categorised DCIS into two major groups that could be further subdivided into subgroups based on the expression of six markers (ER, PR, AR, Bcl-2, p53, and Her2). In the major predominantly ER/Bcl-2-positive (luminal) group, three subgroups (AR-positive (n=33), AR-negative (n=40), and mixed (n=34)) could be identified and included 34 well-differentiated DCISs. Within the major predominantly ER/Bcl-2-negative (nonluminal) group, a Her2-positive subgroup (n=34) was characterised by 31 poorly differentiated lesions. Eight triple-negative lesions, including one positive for keratin 5/6 and two positive for p53, were encountered. Intermediately differentiated DCIS shared a comparable IHC staining pattern with well-differentiated DCIS that was distinct from poorly differentiated DCIS (P<0.001). Ductal carcinoma in situ could be categorised by IHC into two major groups and five subgroups using six markers. Morphologically, intermediately differentiated DCIS seems to have more biological similarities with well-differentiated lesions as compared to poorly differentiated lesions

Photodynamic therapy as adjuvant therapy in surgically treated pleural malignancies.

Five patients with a pleural malignancy (four malignant mesotheliomas and one localized low grade carcinoid) were treated with maximal surgical resection of the tumour followed by intraoperative adjuvant photodynamic therapy (PDT). The additional photodynamic treatment was performed with light of 652 nm from a high power diode laser, and meta-tetrahydroxy phenylchlorin as the photosensitizer. The light delivery to the thoracic cavity was monitored by in situ isotropic light detectors. The position of the light delivery fibre was adjusted to achieve optimal light distribution, taking account of reflected and scattered light in this hollow cavity. There was no 30-day post-operative mortality and only one patient suffered from a major complication (diaphragmatic rupture and haematopericardium). The operation time was increased by a maximum of 1 h to illuminate the total hemithoracic surface with 10 J cm(-2) (incident and scattered light). The effect of the adjuvant PDT was monitored by examination of biopsies taken 24 h after surgery under thoracoscopic guidance. Significant damage, including necrosis, was observed in the marker lesions with remaining malignancy compared with normal tissue samples, which showed only an infiltration with PMN cells and oedema of the striated muscles cells. Of the five patients treated, four are alive with no signs of recurrent tumour with a follow-up of 9-11 months. One patient was diagnosed as having a tumour dissemination in the skin around the thoracoscopy scar and died of abdominal tumour spread. Light delivery to large surfaces for adjuvant PDT is feasible in a relatively short period of time (< 1 h). In situ dosimetry ensures optimal light distribution and allows total doses (incident plus scattered light) to be monitored at different positions within the cavity. This combination of light delivery and dosimetry is well suited for adjuvant treatment with PDT in malignant pleural tumours

Histological type and marker expression of the primary tumour compared with its local recurrence after breast-conserving therapy for ductal carcinoma in situ

We have investigated primary ductal carcinomas in situ (DCIS) of the breast and their local recurrences after breast-conserving therapy (BCT) for histological characteristics and marker expression. Patients who were randomized in the EORTC trial 10853 (wide local excision versus excision plus radiotherapy) and who developed a local recurrence were identified. Histology was reviewed for 116 cases; oestrogen and progesterone receptor status, and HER2/ neu and p53 overexpression were assessed for 71 cases. Comparing the primary DCIS and the invasive or non-invasive recurrence, concordant histology was found in 62%, and identical marker expression in 63%. Although 11% of the recurrences developed at a distance from the primary DCIS, nearly all these showed the same histological and immunohistochemical profile. 5 patients developed well-differentiated DCIS or grade I invasive carcinoma after poorly differentiated DCIS. Although these recurrences occurred in the same quadrant as the primary DCIS, they may be considered as second primary tumours. Only 4 patients developed poorly differentiated DCIS or grade III invasive carcinoma after well differentiated DCIS. We conclude that in most cases the primary DCIS and its local recurrence are related histologically or by marker expression, suggesting that local recurrence usually reflects outgrowth of residual DCIS; progression of well differentiated DCIS towards poorly differentiated DCIS or grade III invasive carcinoma is a non-frequent event. © 2001 Cancer Research Campaign http://www.bjcancer.co

Terrestrial temperature evolution of southern Africa during the late Pleistocene and Holocene:Evidence from the Mfabeni Peatland

The scarcity of suitable high-resolution archives, such as ancient natural lakes, that span beyond the Holocene, hinders long-term late Quaternary temperature reconstructions in southern Africa. Here we target two cores from Mfabeni Peatland, one of the few long continuous terrestrial archives in South Africa that reaches into the Pleistocene, to generate a composite temperature record spanning the last ∼43 kyr. The Mfabeni Peatland has previously been proven suitable for temperature and hydrological reconstructions based on pollen and geochemical proxies. Here we use branched glycerol dialkyl glycerol tetraethers (brGDGTs) preserved in the Mfabeni peatland to derive a new quantitative air temperature record for south-east Africa. Our temperature record generally follows global trends in temperature and atmospheric CO2 concentrations, but is decoupled at times. Annual air temperatures during Marine Isotope Stage (MIS) 3 were moderately high (c. 20.5 °C), but dropped by c. 5 °C during the Last Glacial Maximum, reaching a minimum at c.16–15 ka. Asynchronous with local insolation, this cooling may have resulted from reduced sea surface temperatures linked to a northward shift in the Southern Hemisphere westerly winds. Concurrent with the southward retreat of the westerlies, and increasing sea surface temperatures offshore, warming from minimum temperatures (c. 15.0 °C) to average Holocene temperatures (c. 20.0 °C) occurred across the deglaciation. This warming was briefly but prominently interrupted by a millennial-scale cooling event of c. 3 °C at c. 2.4 ka, concurrent with a sudden change in hydrological conditions. The average Holocene temperatures of c. 20.0 °C were similar to those reconstructed for MIS 3, but after the 2.4 ka cooling period, air temperatures in the Mfabeni peat recovered and steadily increased towards the present. In summary, our record demonstrates that land temperature in eastern South Africa is highly sensitive to global drivers as well as nearby sea surface temperatures

Genetic alterations on chromosome 16 and 17 are important features of ductal carcinoma in situ of the breast and are associated with histologic type

We analysed the involvement of known and putative tumour suppressor- and oncogene loci in ductal carcinoma in situ (DCIS) by microsatellite analysis (LOH), Southern blotting and comparative genomic hybridization (CGH). A total of 78 pure DCIS cases, classified histologically as well, intermediately and poorly differentiated, were examined for LOH with 76 markers dispersed along all chromosome arms. LOH on chromosome 17 was more frequent in poorly differentiated DCIS (70%) compared to well-differentiated DCIS (17%), whereas loss on chromosome 16 was associated with well- and intermediately differentiated DCIS (66%). For a subset we have done Southern blot- and CGH analysis. C-erbB2/neu was amplified in 30% of poorly differentiated DCIS. No amplification was found of c-myc, mdm2, bek, flg and the epidermal growth factor (EGF)-receptor. By CGH, most frequent alterations in poorly differentiated DCIS were gains on 8q and 17q22–24 and deletion on 17p, whereas in well-differentiated DCIS amplification on chromosome 1q and deletion on 16q were found. In conclusion, our data indicates that inactivation of a yet unknown tumour suppressor gene on chromosome 16q is implicated in the development of most well and intermediately differentiated DCIS whereas amplification and inactivation of various genes on chromosome 17 are implicated in the development of poorly differentiated DCIS. Furthermore these data show that there is a genetic basis for the classification of DCIS in a well and poorly differentiated type and support the evidence of different genetic routes to develop a specific type of carcinoma in situ of the breast. © 1999 Cancer Research Campaig

Cost-effectiveness of prophylactic hysterectomy in first-degree female relatives with Lynch syndrome of patients diagnosed with colorectal cancer in the United States: a microsimulation study

Background To evaluate the cost-effectiveness of prophylactic hysterectomy (PH) in women with Lynch syndrome (LS). Methods We developed a microsimulation model incorporating the natural history for the development of hyperplasia with and without atypia into endometrial cancer (EC) based on the MISCAN-framework. We simulated women identified as first-degree relatives (FDR) with LS of colorectal cancer patients after universal testing for LS. We estimated costs and benefits of offering this cohort PH, accounting for reduced quality of life after PH and for having EC. Three minimum ages (30/35/40) and three maximum ages (70/75/80) were compared to no PH. Results In the absence of PH, the estimated number of EC cases was 300 per 1,000 women with LS. Total associated costs for treatment of EC were $5.9 million. Offering PH to FDRs aged 40-80 years was considered optimal. This strategy reduced the number of endometrial cancer cases to 5.4 (-98$15.0 million (+154%) per 1,000 women. PH from earlier ages was more costly and resulted in fewer QALYs, although this finding was sensitive to disutility for PH. Conclusions Offering PH to 40- to 80-year-old women with LS is expected to add 0.5 QALY per person at acceptable costs. Women may decide to have PH at a younger age, depending on their individual disutility for PH and premature menopause.Development and application of statistical models for medical scientific researchAnalysis and support of clinical decision makin

E-cadherin inactivation in lobular carcinoma in situ of the breast: an early event in tumorigenesis.

In breast cancer, inactivating point mutations in the E-cadherin gene are frequently found in invasive lobular carcinoma (ILC) but never in invasive ductal carcinoma (IDC). Lobular carcinoma in situ (LCIS) adjacent to ILC has previously been shown to lack E-cadherin expression, but whether LCIS without adjacent invasive carcinoma also lacks E-cadherin expression and whether the gene mutations present in ILC are already present in LCIS is not known. We report here that E-cadherin expression is absent in six cases of LCIS and present in 150 cases of ductal carcinoma in situ (DCIS), both without an adjacent invasive component. Furthermore, using mutation analysis, we could demonstrate the presence of the same truncating mutations and loss of heterozygosity (LOH) of the wild-type E-cadherin in the LCIS component and in the adjacent ILC. Our results indicate that E-cadherin is a very early target gene in lobular breast carcinogenesis and plays a tumour-suppressive role, additional to the previously suggested invasion-suppressive role

Lipid-biomarker-based sea surface temperature record offshore Tasmania over the last 23 million years

The Neogene (23.04–2.58 Ma) is characterised by progressive buildup of ice volume and climate cooling in the Antarctic and the Northern Hemisphere. Heat and moisture delivery to Antarctica is, to a large extent, regulated by the strength of meridional temperature gradients. However, the evolution of the Southern Ocean frontal systems remains scarcely studied in the Neogene. Here, we present the first long-term continuous sea surface temperature (SST) record of the subtropical front area in the Southern Ocean at Ocean Drilling Program (ODP) Site 1168 off western Tasmania. This site is, at present, located near the subtropical front (STF), as it was during the Neogene, despite a 10∘ northward tectonic drift of Tasmania. We analysed glycerol dialkyl glycerol tetraethers (GDGTs – on 433 samples) and alkenones (on 163 samples) and reconstructed the paleotemperature evolution using TEX86 and U37k′ as two independent quantitative proxies. Both proxies indicate that Site 1168 experienced a temperate ∼ 25 ∘C during the early Miocene (23–17 Ma), reaching ∼ 29 ∘C during the mid-Miocene climatic optimum. The stepwise ∼ 10 ∘C cooling (20–10 ∘C) in the mid-to-late Miocene (12.5–5.0 Ma) is larger than that observed in records from lower and higher latitudes. From the Pliocene to modern (5.3–0 Ma), STF SST first plateaus at ∼ 15 ∘C (3 Ma), then decreases to ∼ 6 ∘C (1.3 Ma), and eventually increases to the modern levels around ∼ 16 ∘C (0 Ma), with a higher variability of 5∘ compared to the Miocene. Our results imply that the latitudinal temperature gradient between the Pacific Equator and the STF during late Miocene cooling increased from 4 to 14 ∘C. Meanwhile, the SST gradient between the STF and the Antarctic margin decreased due to amplified STF cooling compared to the Antarctic margin. This implies a narrowing SST gradient in the Neogene, with contraction of warm SSTs and northward expansion of subpolar conditions.</p