Optimal design of multi-channel microreactor for uniform residence time distribution

Multi-channel microreactors can be used for various applications that require chemical or electrochemical reactions in either liquid, gaseous or multi phase. For an optimal control of the chemical reactions, one key parameter for the design of such microreactors is the residence time distribution of the fluid, which should be as uniform as possible in the series of microchannels that make up the core of the reactor. Based on simplifying assumptions, an analytical model is proposed for optimizing the design of the collecting and distributing channels which supply the series of rectangular microchannels of the reactor, in the case of liquid flows. The accuracy of this analytical approach is discussed after comparison with CFD simulations and hybrid analytical-CFD calculations that allow an improved refinement of the meshing in the most complex zones of the flow. The analytical model is then extended to the case of microchannels with other cross-sections (trapezoidal or circular segment) and to gaseous flows, in the continuum and slip flow regimes. In the latter case, the model is based on second-order slip flow boundary conditions, and takes into account the compressibility as well as the rarefaction of the gas flow

Possible Beneficial Effect of Exercise, by Reducing Oxidative Stress, on the Incidence of Preeclampsia

We hypothesize that regular exercise enhances antioxidative enzymes in pregnant women, which reduce oxidative stress and, thus, the incidence of preeclampsia. Oxidative stress with enhanced lipid peroxide formation could lead to endothelial dysfunction in preeclampsia. Other conditions, such as increased transferrin saturation and decreased iron-binding capacity, directly and indirectly promote the process of oxidative stress and subsequent endothelial dysfunction. Exercise increases oxidative metabolism and produces a prooxidant environment. This acidic environment during exercise (at or beyond anaerobic threshold) promotes oxygen release from hemoglobin and increases in PO2 in tissues, as well as releases iron from transferrin. When exercise is repeated regularly, the body promptly adjusts so that oxidative stress is eliminated or reduced. The body's adaptations to a regular exercise habit seem to have an antioxidant effect. In humans, training effects have been identified with an enhanced activity of antioxidative enzymes. Another concerted adaptation that regular exercise brings to women's bodies is resistance against production of prooxidants by increasing the number of mitochondria. Equally important is a training effect that decreases susceptibility to lipid peroxidation. Evidence suggests that physically active women are less likely to develop preeclampsia. In theory, intracellular and extracellular conditions resulting from regular exercise should counteract the enhancement of oxidative stress, thus interfering with the process leading to endothelial dysfunction. This position paper describes a hypothesis and includes a brief review of exercise physiology and biochemical research in preeclampsia. Unlike other preventive treatments, such as aspirin or calcium supplements, a regular exercise habit leads to a positive and healthy lifestyle without concern of side effects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63167/1/152460901317193558.pd

Germline polymorphisms in SIPA1 are associated with metastasis and other indicators of poor prognosis in breast cancer

INTRODUCTION: There is growing evidence that heritable genetic variation modulates metastatic efficiency. Our previous work using a mouse mammary tumor model has shown that metastatic efficiency is modulated by the GTPase-activating protein encoded by Sipa1 ('signal-induced proliferation-associated gene 1'). The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) within the human SIPA1 gene are associated with metastasis and other disease characteristics in breast cancer. METHOD: The study population (n = 300) consisted of randomly selected non-Hispanic Caucasian breast cancer patients identified from a larger population-based series. Genomic DNA was extracted from peripheral leukocytes. Three previously described SNPs within SIPA1 (one within the promoter [-313G>A] and two exonic [545C>T and 2760G>A]) were characterized using SNP-specific PCR. RESULTS: The variant 2760G>A and the -313G>A allele were associated with lymph node involvement (P = 0.0062 and P = 0.0083, respectively), and the variant 545C>T was associated with estrogen receptor negative tumors (P = 0.0012) and with progesterone negative tumors (P = 0.0339). Associations were identified between haplotypes defined by the three SNPs and disease progression. Haplotype 3 defined by variants -313G>A and 2760G>A was associated with positive lymph node involvement (P = 0.0051), and haplotype 4 defined by variant 545C>T was associated with estrogen receptor and progesterone receptor negative status (P = 0.0053 and P = 0.0199, respectively). CONCLUSION: Our findings imply that SIPA1 germline polymorphisms are associated with aggressive disease behavior in the cohort examined. If these results hold true in other populations, then knowledge of SIPA1 SNP genotypes could potentially enhance current staging protocols

National study of colorectal cancer genetics

Approximately, a third of all colorectal cancer (CRC) is due to inherited susceptibility. However, high-risk mutations in APC, the mismatch repair (MMR) genes, MUTYH/MYH, SMAD4, ALK3 and STK11/LKB1 are rare and account for <5% of cases. Much of the remaining variation in genetic risk is likely to be explained by combinations of more common gene variants that modestly increase risk. Reliable identification of such ‘low penetrance' alleles would provide insight into the aetiology of CRC and might highlight potential therapeutic and preventative interventions. In 2003, the National Study of Colorectal Cancer Genetics (NSCCG) was established with the aim of collecting DNA and clinicopathological data from 20 000 CRC cases and a series of spouse/partner controls, thereby creating a unique resource for identifying low-penetrance CRC susceptibility alleles. The National Cancer Research Network (NCRN) adopted NSCCG onto its portfolio of trials and 148 centres in the United Kingdom (UK) are now actively participating. Over 8700 cases and 2185 controls have so far been entered into NSCCG. Our experience in developing NSCCG serves to illustrate how world-class DNA databases for genetic analyses can be rapidly developed in the United Kingdom

Association of Frequent Aspirin Use With Ovarian Cancer Risk According to Genetic Susceptibility

IMPORTANCE: Frequent aspirin use is associated with reduced ovarian cancer risk, but it is unknown whether genetic factors modify this association. Understanding effect modifiers is important given that any use of aspirin for ovarian cancer chemoprevention will likely need to focus on specific higher-risk subgroups. OBJECTIVE: To evaluate whether the association between frequent aspirin use and ovarian cancer is modified by a polygenic score (PGS) for nonmucinous ovarian cancer. DESIGN, SETTING, AND PARTICIPANTS: We pooled individual-level data from 8 population-based case-control studies from the Ovarian Cancer Association Consortium conducted in the US, UK, and Australia between 1995 and 2009. We included case patients and control participants with both genetic data and data on frequent aspirin use. Case patients with mucinous ovarian cancer were excluded. Data were analyzed between November 1, 2021, and July 31, 2022. EXPOSURES: Frequent aspirin use, defined as daily or almost daily use for 6 months or longer. MAIN OUTCOMES AND MEASURES: The main outcome was nonmucinous epithelial ovarian cancer. We used logistic regression to estimate odds ratios (ORs) and 95% CIs and likelihood ratio tests to investigate effect modification by the PGS. RESULTS: There were 4476 case patients with nonmucinous ovarian cancer and 6659 control participants included in this analysis. At study enrollment, the median (IQR) age was 58 (50-66) years for case patients and 57 (49-65) years for control participants. Case patients and control participants self-reported that they were Black (122 [3%] vs 218 [3%]), White (3995 [89%] vs 5851 [88%]), or of other race and ethnicity (348 [8%] vs 580 [9%]; race and ethnicity were unknown for 11 [0%] vs 10 [0%]). There were 575 case patients (13%) and 1030 control participants (15%) who reported frequent aspirin use. The 13% reduction in ovarian cancer risk associated with frequent aspirin use (OR, 0.87 [95% CI, 0.76-0.99]) was not modified by the PGS. Consistent ORs were observed among individuals with a PGS less than (0.85 [0.70-1.02]) and greater than (0.86 [0.74-1.01]) the median. Results were similar by histotype. CONCLUSIONS AND RELEVANCE: The findings of this study suggest that genetic susceptibility to ovarian cancer based on currently identified common genetic variants does not appear to modify the protective association between frequent aspirin use and ovarian cancer risk. Future work should continue to explore the role of aspirin use for ovarian cancer prevention among individuals who are at higher risk for ovarian cancer

An evaluation of pharmacology curricula in Australian science and health-related degree programs

Background: Pharmacology is a biomedical discipline taught in basic science and professional degree programs. In order to provide information that would facilitate pharmacology curricula to be refined and developed, and approaches to teaching to be updated, a national survey was undertaken in Australia that investigated pharmacology course content, teaching and summative assessment methods. Methods: Twenty-two institutions participated in a purpose-built online questionnaire, which enabled an evaluation of 147 courses taught in 10 different degrees. To enable comparison, degrees were grouped into four major degree programs, namely science, pharmacy, medicine and nursing. The pharmacology content was then classified into 16 lecture themes, with 2-21 lecture topics identified per theme. The resultant data were analysed for similarities and differences in pharmacology curricula across the degree programs. Results: While all lecture themes were taught across degree programs, curriculum content differed with respect to the breadth and hours of coverage. Overall, lecture themes were taught most broadly in medicine and with greatest coverage in pharmacy. Reflecting a more traditional approach, lectures were a dominant teaching method (at least 90% of courses). Sixty-three percent of science courses provided practical classes but such sessions occurred much less frequently in other degree programs, while tutorials were much more common in pharmacy degree programs (70%). Notably, problem-based learning was common across medical programs. Considerable diversity was found in the types of summative assessment tasks employed. In science courses the most common form of in-semester assessment was practical reports, whereas in other programs pen-and-paper quizzes predominated. End-of-semester assessment contributed 50-80% to overall assessment across degree programs. Conclusion: The similarity in lecture themes taught across the four different degree programs shows that common knowledge- and competency-based learning outcomes can be defined for pharmacology. The authors contend that it is the differences in breadth and coverage of material for each lecture theme, and the differing teaching modes and assessment that characterise particular degree programs. Adoption of pharmacology knowledge-based learning outcomes that could be tailored to suit individual degree programs would better facilitate the sharing of expertise and teaching practice than the current model where pharmacology curricula are degree-specific.Hilary Lloyd, Tina Hinton, Shane Bullock, Anna-Marie Babey, Elizabeth Davis, Lynette Fernandes, Joanne Hart, Ian Musgrave and James Zioga

Effect of reproductive factors on stage, grade and hormone receptor status in early-onset breast cancer

INTRODUCTION: Women younger than 35 years who are diagnosed with breast cancer tend to have more advanced stage tumors and poorer prognoses than do older women. Pregnancy is associated with elevated exposure to estrogen, which may influence the progression of breast cancer in young women. The objective of the present study was to examine the relationship between reproductive events and tumor stage, grade, estrogen receptor and progesterone receptor status, and survival in women diagnosed with early-onset breast cancer. METHODS: In a population-based, case–case study of 254 women diagnosed with invasive breast cancer at age under 35 years, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression with tumor characteristics as dependent variables and adjusting for age and education. Survival analyses also examined the relationship between reproductive events and overall survival. RESULTS: Compared with nulliparous women, women with three or more childbirths were more likely to be diagnosed with nonlocalized tumors (OR = 3.1, 95% CI = 1.3–7.7), and early age (<20 years) at first full-term pregnancy was also associated with a diagnosis of breast cancer that was nonlocalized (OR = 3.0, 95% CI = 1.2–7.4) and of higher grade (OR = 3.2, 95% CI 1.0–9.9). The hazard ratio for death among women with two or more full-term pregnancies, as compared with those with one full-term pregnancy or none, was 2.1 (95% CI = 1.0–4.5), adjusting for stage. Among parous women, those who lactated were at decreased risk for both estrogen receptor and progesterone receptor negative tumors (OR = 0.2, 95% CI = 0.1–0.5, and OR = 0.4, 95% CI = 0.2–0.8, respectively). CONCLUSION: The results of the present study suggest that pregnancy and lactation may influence tumor presentation and survival in women with early-onset breast cancer