Increasing Spatial Fidelity and SNR of 4D-STEM using Multi-frame Data Fusion

4D-STEM, in which the 2D diffraction plane is captured for each 2D scan position in the scanning transmission electron microscope (STEM) using a pixelated detector, is complementing and increasingly replacing existing imaging approaches. However, at present the speed of those detectors, although having drastically improved in the recent years, is still 100 to 1,000 times slower than the current PMT technology operators are used to. Regrettably, this means environmental scanning-distortion often limits the overall performance of the recorded 4D data. Here we present an extension of existing STEM distortion correction techniques for the treatment of 4D-data series. Although applicable to 4D-data in general, we use electron ptychography and electric-field mapping as model cases and demonstrate an improvement in spatial-fidelity, signal-to-noise ratio (SNR), phase-precision and spatial-resolution

Compression forces used in the Norwegian Breast Cancer Screening Program

Objectives: Compression is used in mammography to reduce breast thickness, which is claimed to improve image quality and reduce radiation dose. In the Norwegian Breast Cancer Screening Program (NBCSP), the recommended range of compression force for full field digital mammography is 11-18 kg (108-177 Newton [N]). This is the first study to investigate the compression force used in the program. Methods: The study included information from 17,951 randomly selected women screened with FFDM at 14 breast centres in the NBCSP, January-March 2014. We investigated the applied compression force on left breast in craniocaudal (CC) and mediolateral oblique (MLO) view for breast centres, mammography machines within the breast centres and for the radiographers. Results: The mean compression force for all mammograms in the study was 116N and ranged from 91 to 147N between the breast centres. The variation in compression force was wider between the breast centres than between mammography machines (range 137-155N) and radiographers (95-143N) within one breast centre. Approximately 59% of the mammograms in the study complied with the recommended range of compression force. Conclusions: A wide variation in applied compression force was observed between the breast centres in the NBCSP. This variation indicates a need for evidence-based recommendations for compression force aimed at optimizing the image quality and individualising breast compression. Advances in knowledge: There was a wide variation in applied compression force between the breast centres in the NBCSP. The variation was wider between the breast centres than between mammography machines and radiographers within one breast centre

Sister Mary Joseph's Nodule at a University Teaching Hospital in Northwestern Tanzania: A Retrospective Review of 34 cases.

Sister Mary Joseph's nodule is a metastatic tumor deposit in the umbilicus and often represents advanced intra-abdominal malignancy with dismal prognosis. There is a paucity of published data on this subject in our setting. This study was conducted to describe the clinicopathological presentation and treatment outcome of this condition in our environment and highlight challenges associated with the care of these patients, and to proffer solutions for improved outcome. This was a retrospective study of histologically confirmed cases of Sister Mary Joseph's nodule seen at Bugando Medical Centre between March 2003 and February 2013. Data collected were analyzed using descriptive statistics. A total of 34 patients were enrolled in the study. Males outnumbered females by a ratio of 1.4:1. The vast majority of patients (70.6%) presented with large umbilical nodule > 2 cm in size. The stomach (41.1%) was the most common location of the primary tumor. Adenocarcinoma (88.2%) was the most frequent histopathological type. Most of the primary tumors (52.9%) were poorly differentiated. As the disease was advanced and metastatic in all patients, only palliative therapy was offered. Out of 34 patients, 11 patients died in the hospital giving a mortality rate of 32.4%. Patients were followed up for 24 months. At the end of the follow-up period, 14(60.9%) patients were lost to follow-up and the remaining 9 (39.1%) patients died. Patients survived for a median period of 28 weeks (range, 2 to 64 weeks). The nodule recurred in 6 (26.1%) patients after complete excision. Sister Mary Joseph's nodule of the umbilicus is not rare in our environment and often represents manifestation of a variety of advanced intra-abdominal malignancies. The majority of the patients present at a late stage and many with distant metastases. The patient's survival is very short leading to a poor outcome. Early detection of primary cancer at an early stage may improve the prognosis

Evaluation of the cytotoxic effects of the novel antineoplastic agent 1,4,5-Oxathiazinane-4,4-dioxide on triple negative breast cancer cells

Background/Aim: Adjuvant therapeutic options are limited for triple negative breast cancer (TNBC). Thus, we evaluated the cytotoxic effects of the newly synthesized antineoplastic agent 1,4,5-Oxathiazinane-4,4-dioxide (OTD) on TNBC cells as a potential cancer therapeutic strategy. Materials and Methods: TNBC primary BT-20 and metastatic MDA-MB-231 cell lines were treated with increasing concentrations of OTD for various time periods to assess cell viability. Cell necrosis, apoptosis, necroptosis, autophagy, and ROS generation were evaluated using assay kits or specific inhibitors. Results: Treatment with OTD resulted in a dose-and time-dependent cell death of TNBC BT-20 and MDA-MB-231 cells. OTD also dose-dependently arrested TNBC cell proliferation. Notably, treatment with OTD induced both necrosis and apoptosis of TNBC cells, while the pan-caspase inhibitor Z-VAD-FMK partially attenuated OTD-induced cell death. Importantly, abrogated OTD-induced cell death was observed in the presence of the ROS scavenger N-acetylcysteine (NAC), whereas enhanced OTD-induced cell death was observed after the addition of the glutathione synthesis inhibitor BSO, indicating OTDinduced killing of TNBC cells via a reactive oxygen species dependent mechanism. Conclusion: OTD is strongly cytotoxic to both primary and metastatic TNBC cells, possibly by inducing multiple cell death pathways

RandomiSed clinical trial assessing Use of an anti-inflammatoRy aGent in attenUating peri-operatiVe inflAmmatioN in non-meTastatic colon cancer – the S.U.R.G.U.V.A.N.T. trial

Background: Peri-operative inflammation has been extensively highlighted in cancer patients as detrimental. Treatment strategies to improve survival for cancer patients through targeting peri-operative inflammation have yet to be devised. Methods: We conducted a multi-centre, randomised controlled clinical trial using Taurolidine in non-metastatic colon cancer patients. Patients were randomly assigned to receive Taurolidine or a placebo. The primary endpoint for the study was the mean difference in day 1 IL-6 levels. Secondary clinical endpoints included rates of post-operative infections and tumor recurrence. Results: A total of 293 patients were screened for trial inclusion. Sixty patients were randomised. Twenty-eight patients were randomised to placebo and 32 patients to Taurolidine. IL-6 levels were equivalent on day 1 post-operatively in both groups. However, IL-6 levels were significantly attenuated over the 7 day study period in the Taurolidine group compared to placebo (p = 0.04). In addition, IL-6 levels were significantly lower at day 7 in the Taurolidine group (p = 0.04). There were 2 recurrences in the placebo group at 2 years and 1 in the Taurolidine group. The median time to recurrence was 19 months in the Placebo group and 38 months in the Taurolidine group (p = 0.27). Surgical site infection was reduced in the Taurolidine treated group (p = 0.09). Conclusion: Peri-operative use of Taurolidine significantly attenuated circulating IL-6 levels in the initial 7 day post-operative period in a safe manner. Future studies are required to establish the impact of IL-6 attenuation on survival outcomes in colon cancer. Trial registration: The trial was registered with EudraCT (year = 2008, registration number = 005570–12) and ISRCTN (year = 2008, registration number = 77,829,558)

Direct Imaging of Charge Redistribution due to Bonding at Atomic Resolution via Electron Ptychography

Phase imaging in electron microscopy is sensitive to the local potential including charge redistribution from bonding. We demonstrate that electron ptychography provides the necessary sensitivity to detect this subtle effect by directly imaging the charge redistribution in single layer boron nitride. Residual aberrations can be measured and corrected post-collection, and simultaneous atomic number contrast imaging provides unambiguous sub-lattice identification. Density functional theory calculations confirm the detection of charge redistribution

Activation of both TLR and NOD signaling confers host innate immunity-mediated protection against microbial infection

The detection of microbial pathogens relies on the recognition of highly conserved microbial structures by the membrane sensor Toll-like receptors (TLRs) and cytosolic sensor NOD-like receptors (NLRs). Upon detection, these sensors trigger innate immune responses to eradicate the invaded microbial pathogens. However, it is unclear whether TLR and NOD signaling are both critical for innate immunity to initiate inflammatory and antimicrobial responses against microbial infection. Here we report that activation of both TLR and NOD signaling resulted in an augmented inflammatory response and the crosstalk between TLR and NOD led to an amplified downstream NF-kB activation with increased nuclear transactivation of p65 at TNF-a and IL-6 promoters. Furthermore, co-stimulation of macrophages with TLR and NOD agonists maximized antimicrobial activity with accelerated phagosome maturation. Importantly, administration of both TLR and NOD agonists protected mice against polymicrobial sepsis-associated lethality with increased serum levels of inflammatory cytokines and accelerated bacterial clearance from the circulation and visceral organs. These results demonstrate that activation of both TLR and NOD signaling synergizes to induce efficient inflammatory and antimicrobial responses, thus conferring protection against microbial infection

A rhetoric-in-context approach to building commitment to multiple strategic goals

There are still few explanations of the micro-level practices by which top managers influence employee commitment to multiple strategic goals. This paper argues that, through their language, top managers can construct a context for commitment to multiple strategic goals. We therefore propose a rhetoric-in-context approach to illuminate some of the micro practices through which top managers influence employee commitment. Based upon an empirical study of the rhetorical practices through which top managers influence academic commitment to multiple strategic goals in university contexts, we demonstrate relationships between rhetoric and context. Specifically, we show that rhetorical influences over commitment to multiple goals are associated with the historical context for multiple goals, the degree to which top managers' rhetoric instantiates a change in that context, and the internal consistency of the rhetorical practices used by top managers. Copyright © 2007 SAGE Publications

Patterns of adiposity, vascular phenotypes and cognitive function in the 1946 British Birth Cohort.

BACKGROUND: The relationship between long-term exposure to whole body or central obesity and cognitive function, as well as its potential determinants, remain controversial. In this study, we assessed (1) the potential impact of 30 years exposure to different patterns of whole body and central adiposity on cognitive function at 60-64 years, (2) whether trajectories of central adiposity can provide additional information on later cognitive function compared to trajectories of whole body adiposity, and (3) the influence of vascular phenotypes on these associations. METHODS: The study included 1249 participants from the prospective cohort MRC National Survey of Health and Development. Body mass index (BMI), waist circumference (WC), and vascular (carotid intima-media thickness, carotid-femoral pulse wave velocity) and cognitive function (memory, processing speed, reaction time) data, at 60-64 years, were used to assess the associations between different patterns of adult WC or BMI (from 36 years of age) and late midlife cognitive performance, as well as the proportion of this association explained by cardiovascular phenotypes. RESULTS: Longer exposure to elevated WC was related to lower memory performance (p < 0.001 for both) and longer choice reaction time (p = 0.003). A faster gain of WC between 36 and 43 years of age was associated with the largest change in reaction time and memory test (P < 0.05 for all). Similar associations were observed when patterns of WC were substituted with patterns of BMI, but when WC and BMI were included in the same model, only patterns of WC remained significantly associated with cognitive function. Participants who dropped one BMI category and maintained a lower BMI had similar memory performance to those of normal weight during the whole follow-up. Conversely, those who dropped and subsequently regained one BMI category had a memory function similar to those with 30 years exposure to elevated BMI. Adjustment for vascular phenotypes, levels of cardiovascular risk factors, physical activity, education, childhood cognition and socioeconomic position did not affect these associations. CONCLUSIONS: Longer exposure to elevated WC or BMI and faster WC or BMI gains between 36 and 43 years are related to lower cognitive function at 60-64 years. Patterns of WC in adulthood could provide additional information in predicting late midlife cognitive function than patterns of BMI. The acquisition of an adverse cardiovascular phenotype associated with adiposity is unlikely to account for these relationships