Temperature-dependent magnetic particle imaging with multi-harmonic lock-in detection

Advances in instrumentation and tracer materials are still required to enable sensitive and accurate 3D temperature monitoring by magnetic particle imaging. We have developed a magnetic particle imaging instrument to observe temperature variations using MPI, and discuss resolution dependence on temperature and harmonic number. Furthermore, we present a low noise approach using lock-in detection for temperature measurement, and discuss implications for a new detection modality of MPI.Comment: 26 pages, 17 figure

Toward Predicting Success and Failure in CS2: A Mixed-Method Analysis

Factors driving success and failure in CS1 are the subject of much study but less so for CS2. This paper investigates the transition from CS1 to CS2 in search of leading indicators of success in CS2. Both CS1 and CS2 at the University of North Carolina Wilmington (UNCW) are taught in Python with annual enrollments of 300 and 150 respectively. In this paper, we report on the following research questions: 1) Are CS1 grades indicators of CS2 grades? 2) Does a quantitative relationship exist between CS2 course grade and a modified version of the SCS1 concept inventory? 3) What are the most challenging aspects of CS2, and how well does CS1 prepare students for CS2 from the student's perspective? We provide a quantitative analysis of 2300 CS1 and CS2 course grades from 2013--2019. In Spring 2019, we administered a modified version of the SCS1 concept inventory to 44 students in the first week of CS2. Further, 69 students completed an exit questionnaire at the conclusion of CS2 to gain qualitative student feedback on their challenges in CS2 and on how well CS1 prepared them for CS2. We find that 56% of students' grades were lower in CS2 than CS1, 18% improved their grades, and 26% earned the same grade. Of the changes, 62% were within one grade point. We find a statistically significant correlation between the modified SCS1 score and CS2 grade points. Students identify linked lists and class/object concepts among the most challenging. Student feedback on CS2 challenges and the adequacy of their CS1 preparations identify possible avenues for improving the CS1-CS2 transition.Comment: The definitive Version of Record was published in 2020 ACM Southeast Conference (ACMSE 2020), April 2-4, 2020, Tampa, FL, USA. 8 page

Technologies of birth and models of midwifery care

This article is based on a study of a reform in the organisation of maternity services in the United Kingdom, which aimed towards developing a more woman-centred model of care. After decades of fragmentation and depersonalisation of care, associated with the shift of birth to a hospital setting, pressure by midwives and mothers prompted government review and a relatively radical turnaround in policy. However, the emergent model of care has been profoundly influenced by concepts and technologies of monitoring. The use of such technologies as ultrasound scans, electronic foetal monitoring and oxytocic augmentation of labour, generally supported by epidural anaesthesia for pain relief, have accompanied the development of a particular ecological model of birth – often called active management –, which is oriented towards the idea of an obstetric norm. Drawing on analysis of women’s narrative accounts of labour and birth, this article discusses the impact on women’s embodiment in birth, and the sources of information they use about the status of their own bodies, their labour and that of the child. It also illustrates how the impact on women’s experiences of birth may be mediated by a relational model of support, through the provision of caseload midwifery care

Depression, anxiety, stress, social interaction and health-related quality of life in men and women with unexplained chest pain

<p>Abstract</p> <p>Background</p> <p>Unexplained chest pain (UCP) is a common reason for emergency hospital admission and generates considerable health-care costs for society. Even though prior research indicates that psychological problems and impaired quality of life are common among UCP patients, there is lack of knowledge comparing UCP patients with a reference group from the general population. The aim of this study was to analyse differences between men and women with UCP and a reference group in terms of psychosocial factors as depression, anxiety, stress, social interaction and health-related quality of life (HRQOL).</p> <p>Methods</p> <p>A self-administered questionnaire about psychosocial factors was completed by 127 men and 104 women with acute UCP admitted consecutively to the Emergency Department (ED) or as in-patients on a medical ward. A reference group from the general population, 490 men and 579 women, participants in the INTERGENE study and free of clinical heart disease, were selected.</p> <p>Results</p> <p>The UCP patients were more likely to be immigrants, have a sedentary lifestyle, report stress at work and have symptoms of depression and trait-anxiety compared with the reference group. After adjustment for differences in age, smoking, hypertension and diabetes, these factors were still significantly more common among patients with UCP. In a stepwise multivariate model with mutual adjustment for psychosocial factors, being an immigrant was associated with a more than twofold risk in both sexes. Stress at work was associated with an almost fourfold increase in risk among men, whereas there was no independent impact for women. In contrast, depression only emerged as an independent risk factor in women. Trait-anxiety and a low level of social interaction were not independently associated with risk in either men or women. Patients with UCP were two to five times more likely to have low scores for HRQOL.</p> <p>Conclusion</p> <p>Both men and women with UCP had higher depression scores than referents, but an independent association was only found in women. Among men, perceived stress at work emerged as the only psychosocial variable significantly associated with UCP.</p

Phase 2 study of canfosfamide in combination with pegylated liposomal doxorubicin in platinum and paclitaxel refractory or resistant epithelial ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Canfosfamide is a novel glutathione analog activated by glutathione S-transferase P1-1. This study evaluated the safety and efficacy of canfosfamide in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum resistant ovarian cancer. Patients with platinum resistant ovarian carcinoma and measurable disease received canfosfamide at 960 mg/m²in combination with PLD at 50 mg/m², intravenously day 1 in every 28 day cycles until tumor progression or unacceptable toxicities. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS).</p> <p>Results</p> <p>Canfosfamide plus PLD combination therapy was administered at 960/50 mg/m², respectively. Thirty-nine patients received a median number of 4 cycles (range 1.0-18.0). The ORR was 27.8% (95% CI, 14.2-45.2) with a disease stabilization rate of 80.6% (95% CI, 64.0-91.8) in the evaluable population. The CA-125 marker responses correlated with the radiological findings of complete response or partial response. The median PFS was 6.0 months (95% CI, 4.2-7.9) and median survival was 17.8 months. The combination was well tolerated. Myelosuppression was managed with dose reductions and growth factor support. Grade 3 febrile neutropenia was observed in 2 patients (5.1%). Non-hematologic adverse events occurred at the expected frequency and grade for each drug alone, with no unexpected or cumulative toxicities.</p> <p>Conclusions</p> <p>Canfosfamide in combination with PLD is well tolerated and active in platinum and paclitaxel refractory or resistant ovarian cancer. A randomized phase 3 study was conducted based on this supportive phase 2 study.</p> <p>Trial Registration</p> <p>This study was registered at www.clinicaltrials.gov: NCT00052065.</p

Cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma, laryngeal and hepatocarcinoma cells in vitro

<p>Abstract</p> <p>Background</p> <p>Cholangiocarcinoma is a serious public health in Thailand with increasing incidence and mortality rates. The present study aimed to investigate cytotoxic activities of crude ethanol extracts of a total of 28 plants and 5 recipes used in Thai folklore medicine against human cholangiocarcinoma (CL-6), human laryngeal (Hep-2), and human hepatocarcinoma (HepG2) cell lines in vitro.</p> <p>Methods</p> <p>Cytotoxic activity of the plant extracts against the cancerous cell lines compared with normal cell line (renal epithelial cell: HRE) were assessed using MTT assay. 5-fluorouracil was used as a positive control. The IC₅₀(concentration that inhibits cell growth by 50%) and the selectivity index (SI) were calculated.</p> <p>Results</p> <p>The extracts from seven plant species (<it>Atractylodes lancea</it>, <it>Kaempferia galangal</it>, <it>Zingiber officinal</it>, <it>Piper chaba</it>, <it>Mesua ferrea</it>, <it>Ligusticum sinense</it>, <it>Mimusops elengi</it>) and one folklore recipe (Pra-Sa-Prao-Yhai) exhibited promising activity against the cholangiocarcinoma CL-6 cell line with survival of less than 50% at the concentration of 50 μg/ml. Among these, the extracts from the five plants and one recipe (<it>Atractylodes lancea</it>, <it>Kaempferia galangal</it>, <it>Zingiber officinal</it>, <it>Piper chaba</it>, <it>Mesua ferrea</it>, and Pra-Sa-Prao-Yhai recipe) showed potent cytotoxic activity with mean IC₅₀values of 24.09, 37.36, 34.26, 40.74, 48.23 and 44.12 μg/ml, respectively. All possessed high activity against Hep-2 cell with mean IC₅₀ranging from 18.93 to 32.40 μg/ml. In contrast, activity against the hepatoma cell HepG2 varied markedly; mean IC₅₀ranged from 9.67 to 115.47 μg/ml. The only promising extract was from <it>Zingiber officinal </it>(IC₅₀= 9.67 μg/ml). The sensitivity of all the four cells to 5-FU also varied according to cell types, particularly with CL-6 cell (IC₅₀= 757 micromolar). The extract from <it>Atractylodes lancea </it>appears to be both the most potent and most selective against cholangiocarcinoma (IC₅₀= 24.09 μg/ml, SI = 8.6).</p> <p>Conclusions</p> <p>The ethanolic extracts from five plants and one folklore recipe showed potent cytotoxic activity against CL-6 cell. Sensitivity to other cancerous cell lines varied according to cell types and the hepatocarcinoma cell line. HepG2 appears to be the most resistant to the tested extracts.</p

Biochemical Comparison of Anopheles gambiae and Human NADPH P450 Reductases Reveals Different 2′-5′-ADP and FMN Binding Traits

NADPH-cytochrome P450 oxidoreductase (CPR) plays a central role in chemical detoxification and insecticide resistance in Anopheles gambiae, the major vector for malaria. Anopheles gambiae CPR (AgCPR) was initially expressed in Eschericia coli but failed to bind 2′, 5′-ADP Sepharose. To investigate this unusual trait, we expressed and purified a truncated histidine-tagged version for side-by-side comparisons with human CPR. Close functional similarities were found with respect to the steady state kinetics of cytochrome c reduction, with rates (kcat) of 105 s−1 and 88 s−1, respectively, for mosquito and human CPR. However, the inhibitory effects of 2′,5′-ADP on activity were different; the IC50 value of AgCPR for 2′, 5′ –ADP was significantly higher (6–10 fold) than human CPR (hCPR) in both phosphate and phosphate-free buffer, indicative of a decrease in affinity for 2′, 5′- ADP. This was confirmed by isothermal titration calorimetry where binding of 2′,5′-ADP to AgCPR (Kd = 410±18 nM) was ∼10 fold weaker than human CPR (Kd = 38 nM). Characterisation of the individual AgFMN binding domain revealed much weaker binding of FMN (Kd = 83±2.0 nM) than the equivalent human domain (Kd = 23±0.9 nM). Furthermore, AgCPR was an order of magnitude more sensitive than hCPR to the reductase inhibitor diphenyliodonium chloride (IC50 = 28 µM±2 and 361±31 µM respectively). Taken together, these results reveal unusual biochemical differences between mosquito CPR and the human form in the binding of small molecules that may aid the development of ‘smart’ insecticides and synergists that selectively target mosquito CPR

Constructing the HBV-human protein interaction network to understand the relationship between HBV and hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies have clearly validated the association between hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). Patients with chronic HBV infection are at increased risk of HCC, in particular those with active liver disease and cirrhosis.</p> <p>Methods</p> <p>We catalogued all published interactions between HBV and human proteins, identifying 250 descriptions of HBV and human protein interactions and 146 unique human proteins that interact with HBV proteins by text mining.</p> <p>Results</p> <p>Integration of this data set into a reconstructed human interactome showed that cellular proteins interacting with HBV are made up of core proteins that are interconnected with many pathways. A global analysis based on functional annotation highlighted the enrichment of cellular pathways targeted by HBV.</p> <p>Conclusions</p> <p>By connecting the cellular proteins targeted by HBV, we have constructed a central network of proteins associated with hepatocellular carcinoma, which might be to regard as the basis of a detailed map for tracking new cellular interactions, and guiding future investigations.</p